Primary biliary cirrhosis(PBC) is an autoimmune disease of the liver characterized by progressive bile duct destruction eventually leading to cirrhosis and liver failure.The serological hallmark of the disease is the ...Primary biliary cirrhosis(PBC) is an autoimmune disease of the liver characterized by progressive bile duct destruction eventually leading to cirrhosis and liver failure.The serological hallmark of the disease is the presence of circulating antimitochondrial antibodies(AMA).These reflect the presence of autoreactive T and B cells to the culprit antigens,the E2 subunits of mitochondrial 2-oxo-acid dehydrogenase enzymes,chiefly pyruvate dehydrogenase(PDC-E2).The disease results from a combination of genetic and environmental risk factors.Genetic predisposition is indicated by the higher familial incidence of the disease particularly among siblings and the high concordance rate among monozygotic twins.Environmental triggering events appear crucial to disrupt a pre-existing unstable immune tolerance of genetic origin allowing,after a long latency,the emergence of clinical disease.Initiating mimetopes of the vulnerable epitope of the PDC-E2 autoantigen can be derived from microbes that utilize the PDC enzyme or,alternatively,environmental xenobiotics/chemical compounds that modify the structure of native proteins to make them immunogenic.A further alternative as a source of antigen is PDC-E2 derived from apoptotic cells.In the effector phase the biliary ductular cell,by reason of itsproclivity to express the antigen PDC-E2 in the course of apoptosis,undergoes a multilineage immune attack comprised of CD4+ and CD8+ T cells and antibody.In this article,we critically review the available evidence on etiopathogenesis of PBC and present interpretations of complex data,new developments and theories,and nominate directions for future research.展开更多
To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease.METHODSLevels of antinuclear Ab, smooth muscle antibody ...To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease.METHODSLevels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays.RESULTSWe found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1<sup>+</sup> Ab CHC cases showed best overlap with AIH.CONCLUSIONAuto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other.展开更多
Primary sclerosing cholangitis(PSC) is a chronic cholestatic liver disease of unknown etiology but lymphocytic portal tract infiltration is suggestive of an immune-mediated basis for this disease.Associations with inf...Primary sclerosing cholangitis(PSC) is a chronic cholestatic liver disease of unknown etiology but lymphocytic portal tract infiltration is suggestive of an immune-mediated basis for this disease.Associations with inflammatory bowel disease(IBD) especially ulcerative colitis(UC),and with particular autoimmune diseases,as well as the genetic associations further suggest PSC may be an immune-mediated disease.The immunogenetics of PSC have been the subject of active research and several HLA and non-HLA associated genes have been implicated in the development of the disease.Lymphocytes derived from the inflamed gut may enter the liver via the enterohepatic circulation to cause hepatic disease.PSC may be triggered in genetically susceptible individuals by infections or toxins entering the portal circulation through a permeable colon and hence evoking an abnormal immune response.展开更多
AIM: Various side effects have been reported in patients infected with hepatitis C virus (HCV) who were treated with interferon-alpha (IFN-α), including the appearance or exacerbation of underlying autoimmune disease...AIM: Various side effects have been reported in patients infected with hepatitis C virus (HCV) who were treated with interferon-alpha (IFN-α), including the appearance or exacerbation of underlying autoimmune diseases and the development of a variety of organ and non-organ specific autoantibodies (NOSA). However, very few studies in adults have been strictly designed to address: whether the prevalence and the titre of organ and NOSA in serial samples of HCV-treated patients were affected by IFN-α, and the impact of these autoantibodies on the treatment outcome of HCV patients. METHODS: We investigated whether parietal cell autoantibodies (PCA) and/or NOSA were related with treatment-outcome in 57 HCV-treated patients (19 sustained-responders, 16 relapsers, 22 non-responders). Serum samples from patients were studied blindly at three time-points (entry, end of treatment and end of followup). For the detection of autoantibodies we used indirect immunofluorescence, commercial and in-house ELISAs. RESULTS: Sustained biochemical response was associated with ANA-negativity at the entry or end of follow up. Sustained virological response was associated with the absence of PCA at the entry. Combined virological and biochemical sustained response (CVBSR) was associated with the absence of antinuclear antibodies (ANA) at the end of follow up and PCA-negativity at the entry. Sustained virological and CVBSR were associated with a reduction of ANA and SMA titers during therapy. CONCLUSION: Although PCA and/or NOSA seropositivity should not affect the decision to treat HCV patients, the presence of some of them such as ANA, PCA and SMA before treatment or their increase during therapy with IFN- a may predict a worse response, indicating the need for a closer monitoring during treatment of HCV patients positive for these autoantibodies.展开更多
AIM: To determine the prevalence of several autoantibodies in chronic hepatitis C patients, and to find out whether the pattern of autoantibodies was associated with hepatitis C virus (HCV) genotypes. METHODS: Sera fr...AIM: To determine the prevalence of several autoantibodies in chronic hepatitis C patients, and to find out whether the pattern of autoantibodies was associated with hepatitis C virus (HCV) genotypes. METHODS: Sera from 90 consecutive patients with chronic hepatitis C were investigated on the presence of anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (SMA), anti-liver-kidney microsomal type 1 (LKMA1), anti-parietal cell (PCA), anti-thyroid microsomal (TMA), and anti-reticulin (ARA) autoantibodies. The autoantibodies were identified by indirect immunofluorescence. HCV genotypes were determined by a restriction fragment length polymorphism analysis of the amplified 5' noncoding genome region. RESULTS: Forty-six (51.1%) patients were positive for at least one autoantibody. Various antibodies were presented as follows: ANA in 13 (14.4%) patients, SMA in 39 (43.3%), TMA in 2 (2.2%), and ARA in 1 (1.1%) patients. In 9 cases, sera were positive for two autoantibodies (ANA and SMA). AMA, PCA and LKMAI were not detected in the observed sera. HCV genotypes were distributed as follows: 1b in 66 (73.3%) patients, 3a in 18 (20.0%), and 2a in 6 (6.7%) patients. CONCLUSION: A high prevalence of ANA and SMA can be found in chronic hepatitis C patients. Autoantibodies are present at low titre (1:10) in most of the cases. Distribution of the autoantibodies show no differences in the sex groups and between patients infected with different HCV genotypes.展开更多
AIM: To evaluate the diagnostic values of serum autoan tibodies against matrix metalloproteinase-7 (MMP-7) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: The MMP-7 cDNA was cloned from ESCC...AIM: To evaluate the diagnostic values of serum autoan tibodies against matrix metalloproteinase-7 (MMP-7) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: The MMP-7 cDNA was cloned from ESCC tissues, and MMP-7 was expressed and purified from a prokaryotic system. MMP-7 autoanUbodies were then measured in sera from 50 patients with primary ESCC and 58 risk-matched controls, using a reverse capture enzyme-linked immunosorbent assay (ELISA) in which autoantibodies to MMP-7 bound to the purified MMP-7 proteins. In addition, MMP-7 autoantibody levels in sera from 38 gastric cancer patients and from control serum samples were also tested. RESULTS: The optimum conditions for recombinant MMP-7 protein expression were determined as 0.04 mmol/L Isopropyl-13-D-Thiogalactopyranoside (IPTG)induction at 37℃ for four hours. The levels of serum autoantibodies against MMP-7 were significantly higher in patients with ESCC than in the matched-control samples (OD450 = 1.69 ±0.08 vs OD450 = 1.55 ± 0.10, P 〈 0.001). The area under the receiver operating character- istic (ROC) curve was 0.87. The sensitivity and specificity for detection of ESCC were 78.0% and 81.0%, respectively, when the OD450 value was greater than 1.65. Although the levels of autoantibodies against MMP-7 were also significantly higher in patients with gastric cancer compared to control samples (OD450 = 1.62± 0.06 vs OD450 = 1.55±0.10, P 〈 0.001), the diagnostic accuracy was less significant than in ESCC patients. The area of ROC curve was 0.75, whereas the sensitivity and specificity were 60.5% and 71.7%, respectively, when the cut-off value of OD450 was set at 1.60. CONCLUSION: Serum autoantibody levels of MMP-7 may be a good diagnostic biomarker for esophageal squamous cell carcinoma,展开更多
The aetiology of primary sclerosing cholangitis (PSC) is not known and controversy exists as to whether PSC should be denominated an autoimmune disease. A large number of autoantibodies have been detected in PSC patie...The aetiology of primary sclerosing cholangitis (PSC) is not known and controversy exists as to whether PSC should be denominated an autoimmune disease. A large number of autoantibodies have been detected in PSC patients,but the specifi city of these antibodies is generally low,and the frequencies vary largely between different studies. The presence of autoantibodies in PSC may be the result of a nonspecifi c dysregulation of the immune system,but the literature in PSC points to the possible presence of specifi c antibody targets in the biliary epithelium and in neutrophil granulocytes. The present review aims to give an overview of the studies of autoantibodies in PSC,with a particular emphasis on the prevalence,clinical relevance and possible pathogenetic importance of each individual marker.展开更多
We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patien...We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patient presented with polydipsia, polyuria, hypergly-cemia, diabetic ketoacidosis, combined with C-peptide secretion defi ciency and positive islet cell autoantibody (ICAb). IFN-α 2b treatment was terminated and in-stead insulin treatment was initiated. Five months after cessation of the recombinant human IFN-α 2b therapy, the patient remained insulin-dependent. Her serum HBV DNA became negative and serum transaminase returned to the normal level after a 10-mo period of IFN therapy. Type 1 DM induced by IFN-α is relatively rare in patients with chronic hepatitis B. We should pay more attention to patients on IFN-α therapy to avoid destruction of pancreatic beta cells. This is the first case report from China.展开更多
Autoimmune hepatitis(AIH),initially known as chronic active or active chronic hepatitis(and by various other names),first came under clinical notice in the late 1940s.However,quite likely,chronic active hepatitis(CAH)...Autoimmune hepatitis(AIH),initially known as chronic active or active chronic hepatitis(and by various other names),first came under clinical notice in the late 1940s.However,quite likely,chronic active hepatitis(CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver.An earlier(and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E.cell test positivity and emphasized accompanying multisystem features and immunological aberrations.Young women featured prominently in early descriptions of CAH.AIH was first applied in 1965 as a descriptive term.Disease-characteristic autoantibodies were defined from the early 1960s,notably antinuclear antibody(ANA),smooth muscle antibody(SMA) and liver-kidney microsomal(LKM) antibody.These are still widely used diagnostically but their relationship to pathogenesis is still not evident.A liver and disease specific autoantigen has long been searched for but unsuccessfully.Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today.AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8,DR3 haplotype,and also with DR4.Looking forwards,AIH is one of the several enigmatic autoimmune diseases that,despite being(relatively) organ specific,are marked by autoimmune reactivities with non-organ-specific autoantigens.New paradigms are needed to explain the occurrence,expressions and pathogenesis of such diseases.展开更多
Although both primary biliary cirrhosis (PBC) and idiopathic thrombocytopenic purpura (ITP) are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the f...Although both primary biliary cirrhosis (PBC) and idiopathic thrombocytopenic purpura (ITP) are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the follow-up of PBC in a 74-year- old man. The patient had been diagnosed with PBC 12 years previously, and had received treatment with ursodeoxycholic acid. The platelet count decreased from approximately 60 × 109/L to 8 × 109/L, and the association of decompensated liver cirrhosis (PBC) with ITP was diagnosed. Steroid and immune gamma globulin therapy were successful in increasing the platelet count. Interestingly, human leukocyte antigen genotyping detected the alleles DQB10601 and DRB10803, which are related to both PBC and ITP in Japanese patients. This case suggests common immunogenetic factors might be involved in the development of PBC and ITP.展开更多
AIM: To evaluate the prevalence of autoantibodies in chronic hepatitis C virus (HCV)-infected children focusing on thyroid autoimmunity.METHODS: We investigated the prevalence of autoantibodies in 123 chronic HCV-...AIM: To evaluate the prevalence of autoantibodies in chronic hepatitis C virus (HCV)-infected children focusing on thyroid autoimmunity.METHODS: We investigated the prevalence of autoantibodies in 123 chronic HCV-infected children before, during and after monotherapy with interferon-alpha (IFN-α) or combined treatment with interferon-α or peginterferon-α and ribavirin. Besides antibodies against smooth muscle (SMA), nuclei (ANA), and liver/kidney microsomes (1KM), the incidence of antithyroid peroxidase antibodies as well as thyroid function parameters (TSH, FT3 and FT4) were determined.RESULTS: We found that 8% of children had autoantibodies before treatment. During treatment, 18% of children were found positive for at least one autoantibody; 15.5% of children developed pathologic thyroid values during IFN-α treatment compared to only one child before therapy. Six children had to be substituted while developing laboratory signs of hypothyroidism.CONCLUSION: Our data indicate a strong correlation between interferon-α treatment and autoimmune phenomena, notably the emergence of thyroid antibodies. The fact that some children required hormone replacement underlines the need of close monitoring in particularly those who respond to therapy and have to be treated for more than 6 mo.展开更多
A1M: To investigate the prevalence of celiac disease (CD) as well as CD marker antibodies and susceptibility HLA-DQ haplotypes in 134 karyotyped Down's syndrome (DS) patients. METHODS: Immunoglobulin A (IgA) ...A1M: To investigate the prevalence of celiac disease (CD) as well as CD marker antibodies and susceptibility HLA-DQ haplotypes in 134 karyotyped Down's syndrome (DS) patients. METHODS: Immunoglobulin A (IgA) and G (IgG) type anti-gliadin antibodies (AGA), IgA type anti-tissue transglutaminase (tTG) antibodies (anti-tTG) with antigen of guinea pig and human source were determined by enzyme-linked immunosorbent assay and endomysium antibodies (EHA) by indirect immunofiuoresence test. HLA-DQA1*0501/DQB1*0201 (DQ2) was revealed by polymerase chain reaction. Celiac disease was diagnosed by revised ESPGHAN criteria. RESULTS: 41% of DS patients had AGA, 6.0% IgA anti-tTG with guinea pig antigen, and 3.0 % [gA EMA (all positive for anti-tTG with human tTG). Subtotal villous atrophy was found in 5 out of 9 DS patients who had agreed to small bowel biopsy. One of them had DQA1*0S01/DQB1*0201 and anti-tTG and EMA i.e. typical for CD markers (this case also fulfilled the ESPGHAN diagnostic criteria), but other four lacked these markers. Three non-biopsied DS patients had also most probably CD because DQA1*0S01/DQB1*0201 and IgA anti-tTG (EMA) were detected. Thus, the prevalence of CD among our DS patients population is 3.0 % (95 % of confidence interval [CI]: 0.1-5.9 %). CONCLUSION: We confirm the increased frequency of CD among DS patients. In addition, we have revealed a subgroup of patients with subtotal villous atrophy but without characteristic for CD immunological and genetic markers. Whether these cases represent CD (with atypical immunopathogenesis) or some other immune enteropathy, requires further investigations.展开更多
Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental fac...Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental factors,genetic predisposition and loss of immune tolerance.In recent years,it has become univocally accepted that an inappropriately activated immune response is one of the most important factors in PBC.In this study,the role of autoimmunity in PBC is summarized and a feasible research orientation is recommended.展开更多
To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) in murine experimental autoimmune hepatitis (EAH).METHODS: To induce EAH, the syngeneic S-100 antigen emulsified in complete Freud's adju...To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) in murine experimental autoimmune hepatitis (EAH).METHODS: To induce EAH, the syngeneic S-100 antigen emulsified in complete Freud's adjuvant was injected intraperitoneally into adult male C57BI/6 mice. Liver injury was assessed by serum ALT and liver histology. The expression and activity of p38 MAPK were measured by Western blot and kinase activity assays. In addition, DNA binding activities of nuclear factor kappa B (NF-KB) were analyzed by electrophoretic mobility shift assay. The effects of SB203580, a specific p38 MAPK inhibitor, on liver injuries and expression of proinflammatory cytokines (interferon-y, IL-12, IL-1β and TNF-α) were observed.RESULTS: The activity of p38 MAPK and NF-~:B was increased and reached its peak 14 or 21 d after the first syngeneic S-100 administration. Inhibition of p38 MAPK activation by SB203580 decreased the activation of NF-~:B and the expression of proinflammatory cytokines. Moreover, hepatic injuries were improved significantly after SB203580 administration.展开更多
AIM: Celiac disease is characterized by life-long gluten intolerance. Clinical features of patients with celiac disease are variable. Studies about the prevalence of celiac disease in our country are scarce and there...AIM: Celiac disease is characterized by life-long gluten intolerance. Clinical features of patients with celiac disease are variable. Studies about the prevalence of celiac disease in our country are scarce and there is no study on the prevalence of celiac disease in southern Iran. In the current study, clinical, laboratory and histological features of 52 patients with celiac disease were evaluated. METHODS: In a cross sectional study we retrospectively studied the characteristics of 52 celiac patients at Ahwaz JundiShapour University Hospitals (AJSUH) from November 1, 1999 to 1st Sep 2004. Intestinal biopsy and serum antigliadin and anti-endomysium antibodies were used for the diagnosis of patients. Mucosal lesions were classified according to the criteria of Marsh. Antigliadin antibodies were measured with a commercial enzyme-linked immunosorbent assay. Anti-endomysium antibodies were analyzed by indirect immunofluorescence with the use of a section of monkey esophagus. Routine hematological and biochemical analyses and measurement of immunoglobulin levels were undertaken.RESULTS: Male: female ratio was 1.08. The mean + SD patient age was 21 + 4.5 years (range 10-70 years) and the most common symptoms were diarrhea and weight loss (78.8%) followed by fatigue (73.1%), pallor (65.4%), anorexia (40.4%), abdominal distention (32.7%), and failure to thrive (23.1%). Diarrhea and weight loss and fatigue were the most common findings. Iron deficiency anemia was found in 63.2% of patients and this became normal after adoption of a gluten-free diet in all patients. Immunoglobulin A, IgG antigliadin antibodies and IgA anti-endomysium antibodies were found in 33 and 48 cases, 78.8% and 85.4% of patients, respectively. Biopsy of the small intestine revealed that 90.4% of patients had typical lesions according to the Marsh classification. CONCLUSION: Although classical presentation was seen in most of the patients, atypical clinical manifestations of celiac disease should be kept in mind. In particular, patients with uncommon findings, such as short stature, and iron-deficiency anemia, should be screened for celiac disease. Further epidemiological studies in our area in the general population and in high risk groups seem to be indicated.展开更多
To compare the clinical and pathological manifestations of patients with antineutrophil cytoplasmic autoantibodies (ANCA) directed against proteinas e 3 (anti PR3) or myeloperoxidase (anti MPO). Methods. One hundred a...To compare the clinical and pathological manifestations of patients with antineutrophil cytoplasmic autoantibodies (ANCA) directed against proteinas e 3 (anti PR3) or myeloperoxidase (anti MPO). Methods. One hundred and forty patients with ANCA were detected for anti PR3 a nd anti MPO by ELISA. The clinical features at presentation, histopathological characteristics and outcome of all patients who were tested positive for anti P R3 or anti MPO were analysed.Results. In anti PR3 group (n=21), 16 cases (76.2%) had systemic vasculitis , in which Wegener’s granulomatosis prevailed (13 cases, 61.9%). In anti MPO g roup (n=31), 19 cases (61.3%) were diagnosed as systemic vasculitis and 12 case s (38.7%) as microscopic angiitis. For vasculitic patients with anti PR3 and a nti MPO, the disease duration at diagnosis was 9.6±2.0m and 4.4±0.9m respecti vely, P< 0.05;vasculitis activity index (BVAS) and mean number of affected organ were 22.5±2.1, 5.0±0.4 and 25.1±1.7, 4.8±0.4 respectively, P >0.05;upper r espiratory tract, eye and joint involvements were 11(68.8%), 7(43.8%), 11(68.8 %) and 7(36.8%), 2(10.5%), 5(26.3%) respectively, P< 0.05.Although there was no statistical difference in renal involvement between these two groups, patien ts with serum creatine >500 μmol/L were more commonly seen in anti MPO group t han in anti PR3 group, which were 8(42.1%) and 2(12.5%) respectively, P< 0.05 . Ten relapses were seen in anti PR3 group and only 2 in anti MPO group, but t he acute mortality rate in anti MPO group (5/19, 27.4%) was much higher than t hat in anti PR3 group (1/16, 6.3%). Conclusions. Anti PR3 and anti MPO occurred mainly in systemic vasculitis. A large divergence was seen in the disease spectrum between patients with anti PR 3 and those with anti MPO. In particular, upper respiratory tract, eye and join t involvements, granuloma formation and relapse were more prominent in anti PR3 patients. By contrast, the anti MPO patients had a more acute disease onset, m ore rapid progressive renal involvement and a higher acute mortality rate.展开更多
AIM: To obtain the short peptides mimic antigenic epitopes selected by rat natural antibodies to schistosomes, and to explore their immunoprotection against schistosomiasis in mice.METHODS: Adults worm antigens (AWA) ...AIM: To obtain the short peptides mimic antigenic epitopes selected by rat natural antibodies to schistosomes, and to explore their immunoprotection against schistosomiasis in mice.METHODS: Adults worm antigens (AWA) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked transferred immunoblotting methods with normal SD rat sera (NRS). The killing effects on schistosomula with fresh and heat-inactivated sera from SD rats were observed. Then the purified IgG from sera of SD rats was used to biopan a phage random peptide library and 20 randomly selected positive clones were detected by ELISA and 2 of them were sequenced.Sixty female mice were immunized thrice with positive phage clones (0, 2nd, 4th wk). Each mouse was challenged with 40 cercariae, and all mice were killed 42 d after challenge. The worms and the liver eggs were counted. RESULTS: NRS could specifically react to the molecules of 75 000, 47 000, 34 500 and 23 000 of AWA. Sera from SD rats showed that the mortality rate of schistosomula was 76.2%, and when the sera were heat-inactivated in vitro, the mortality rate was decreased to 41.0% after being cultured for 48 h. The specific phages bound to IgG were enriched about 300-folds after three rounds of biopanning. Twenty clones were detected by ELISA, 19 of them bound to the specific IgG of rat sera. Immunization with these epitopes was carried out in mice. Compared with the control groups, the mixture of two mimic peptides could induce 34.9% (P = 0.000) worm reduction and 67.6% (P = 0.000) total liver egg reduction in mice. Two different mimic peptides could respectively induce 31.0% (P = 0.001), 14.5% (P = 0.074) worm reduction and 61.2% (P = 0.000), 35.7% (P = 0.000) total liver egg reduction. The specific antibody could be induced by immunization of the mimic peptides, and the antibody titer in immunized mice reached more than 1:6 400 as detected by ELISA.CONCLUSION: Specific peptides mimic antigenic molecules can be obtained by biopanning the phage random peptide library and a partially protective immunity against schistosome infection can be stimulated by these phage epitopes in mice.展开更多
Objective: To investigate the influence of anti-keratin autoantibodies (AK auto Abs) on telom-erase activity of squamous cell carcinoma cultured in vitro and the mechanisms of the inhibitory effects of AK auto Abs on ...Objective: To investigate the influence of anti-keratin autoantibodies (AK auto Abs) on telom-erase activity of squamous cell carcinoma cultured in vitro and the mechanisms of the inhibitory effects of AK auto Abs on squamous cell carcinoma. Methods: Influence of AK auto Abs on the proliferation of Tca cells was observed by MTT colorimetry. Telomerase activity of cultured Tca cells and human keratinocytes was determined by telomeric repeat amplication protocol-ELISA (TRAP-ELISA) and polyacrylamide gel elec-trophoresis (PAGE). After being treated with AK auto Abs for 36 h at a concentration of 4, 8, 16 mg/L respectively, the changes of telomerase activity of Tea cells were also detected by TRAP-ELISA and PAGE. Results: MTT colorimetric determination showed that the capacity of proliferation of Tca cells correlated negatively with the concentration of AK auto Abs (r= -0. 74, P<0. 01). TRAP-ELISA and PAGE showed that telomerase activity of Tca cells increased significantly compared to that of cultured human keratinocytes (t = 3. 5396, P<0. 01). AK auto Abs at a concentrations of 4, 8, 16 mg/L had significant dose-dependent inhibitory effects on telomerase activity of Tca cells (r= - 0. 8358, P<0. 01). Conclusion: AK auto Abs have a significant dose-dependent inhibitory effect on the proliferation of cultured Tea cells. AK auto Abs inhibit telomerase activity of cultured Tca cells with dose-dependent pattern. It suggests that decrease of telomerase activity may play an important role in the inhibitory effects of AK auto Abs on squamous cell carcinoma.展开更多
文摘Primary biliary cirrhosis(PBC) is an autoimmune disease of the liver characterized by progressive bile duct destruction eventually leading to cirrhosis and liver failure.The serological hallmark of the disease is the presence of circulating antimitochondrial antibodies(AMA).These reflect the presence of autoreactive T and B cells to the culprit antigens,the E2 subunits of mitochondrial 2-oxo-acid dehydrogenase enzymes,chiefly pyruvate dehydrogenase(PDC-E2).The disease results from a combination of genetic and environmental risk factors.Genetic predisposition is indicated by the higher familial incidence of the disease particularly among siblings and the high concordance rate among monozygotic twins.Environmental triggering events appear crucial to disrupt a pre-existing unstable immune tolerance of genetic origin allowing,after a long latency,the emergence of clinical disease.Initiating mimetopes of the vulnerable epitope of the PDC-E2 autoantigen can be derived from microbes that utilize the PDC enzyme or,alternatively,environmental xenobiotics/chemical compounds that modify the structure of native proteins to make them immunogenic.A further alternative as a source of antigen is PDC-E2 derived from apoptotic cells.In the effector phase the biliary ductular cell,by reason of itsproclivity to express the antigen PDC-E2 in the course of apoptosis,undergoes a multilineage immune attack comprised of CD4+ and CD8+ T cells and antibody.In this article,we critically review the available evidence on etiopathogenesis of PBC and present interpretations of complex data,new developments and theories,and nominate directions for future research.
文摘To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease.METHODSLevels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays.RESULTSWe found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1<sup>+</sup> Ab CHC cases showed best overlap with AIH.CONCLUSIONAuto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other.
文摘Primary sclerosing cholangitis(PSC) is a chronic cholestatic liver disease of unknown etiology but lymphocytic portal tract infiltration is suggestive of an immune-mediated basis for this disease.Associations with inflammatory bowel disease(IBD) especially ulcerative colitis(UC),and with particular autoimmune diseases,as well as the genetic associations further suggest PSC may be an immune-mediated disease.The immunogenetics of PSC have been the subject of active research and several HLA and non-HLA associated genes have been implicated in the development of the disease.Lymphocytes derived from the inflamed gut may enter the liver via the enterohepatic circulation to cause hepatic disease.PSC may be triggered in genetically susceptible individuals by infections or toxins entering the portal circulation through a permeable colon and hence evoking an abnormal immune response.
文摘AIM: Various side effects have been reported in patients infected with hepatitis C virus (HCV) who were treated with interferon-alpha (IFN-α), including the appearance or exacerbation of underlying autoimmune diseases and the development of a variety of organ and non-organ specific autoantibodies (NOSA). However, very few studies in adults have been strictly designed to address: whether the prevalence and the titre of organ and NOSA in serial samples of HCV-treated patients were affected by IFN-α, and the impact of these autoantibodies on the treatment outcome of HCV patients. METHODS: We investigated whether parietal cell autoantibodies (PCA) and/or NOSA were related with treatment-outcome in 57 HCV-treated patients (19 sustained-responders, 16 relapsers, 22 non-responders). Serum samples from patients were studied blindly at three time-points (entry, end of treatment and end of followup). For the detection of autoantibodies we used indirect immunofluorescence, commercial and in-house ELISAs. RESULTS: Sustained biochemical response was associated with ANA-negativity at the entry or end of follow up. Sustained virological response was associated with the absence of PCA at the entry. Combined virological and biochemical sustained response (CVBSR) was associated with the absence of antinuclear antibodies (ANA) at the end of follow up and PCA-negativity at the entry. Sustained virological and CVBSR were associated with a reduction of ANA and SMA titers during therapy. CONCLUSION: Although PCA and/or NOSA seropositivity should not affect the decision to treat HCV patients, the presence of some of them such as ANA, PCA and SMA before treatment or their increase during therapy with IFN- a may predict a worse response, indicating the need for a closer monitoring during treatment of HCV patients positive for these autoantibodies.
文摘AIM: To determine the prevalence of several autoantibodies in chronic hepatitis C patients, and to find out whether the pattern of autoantibodies was associated with hepatitis C virus (HCV) genotypes. METHODS: Sera from 90 consecutive patients with chronic hepatitis C were investigated on the presence of anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (SMA), anti-liver-kidney microsomal type 1 (LKMA1), anti-parietal cell (PCA), anti-thyroid microsomal (TMA), and anti-reticulin (ARA) autoantibodies. The autoantibodies were identified by indirect immunofluorescence. HCV genotypes were determined by a restriction fragment length polymorphism analysis of the amplified 5' noncoding genome region. RESULTS: Forty-six (51.1%) patients were positive for at least one autoantibody. Various antibodies were presented as follows: ANA in 13 (14.4%) patients, SMA in 39 (43.3%), TMA in 2 (2.2%), and ARA in 1 (1.1%) patients. In 9 cases, sera were positive for two autoantibodies (ANA and SMA). AMA, PCA and LKMAI were not detected in the observed sera. HCV genotypes were distributed as follows: 1b in 66 (73.3%) patients, 3a in 18 (20.0%), and 2a in 6 (6.7%) patients. CONCLUSION: A high prevalence of ANA and SMA can be found in chronic hepatitis C patients. Autoantibodies are present at low titre (1:10) in most of the cases. Distribution of the autoantibodies show no differences in the sex groups and between patients infected with different HCV genotypes.
基金Supported by Science and Technology Projects of Hebei Province, #10396107DNIH Grant CA137570 (Zhong L)
文摘AIM: To evaluate the diagnostic values of serum autoan tibodies against matrix metalloproteinase-7 (MMP-7) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: The MMP-7 cDNA was cloned from ESCC tissues, and MMP-7 was expressed and purified from a prokaryotic system. MMP-7 autoanUbodies were then measured in sera from 50 patients with primary ESCC and 58 risk-matched controls, using a reverse capture enzyme-linked immunosorbent assay (ELISA) in which autoantibodies to MMP-7 bound to the purified MMP-7 proteins. In addition, MMP-7 autoantibody levels in sera from 38 gastric cancer patients and from control serum samples were also tested. RESULTS: The optimum conditions for recombinant MMP-7 protein expression were determined as 0.04 mmol/L Isopropyl-13-D-Thiogalactopyranoside (IPTG)induction at 37℃ for four hours. The levels of serum autoantibodies against MMP-7 were significantly higher in patients with ESCC than in the matched-control samples (OD450 = 1.69 ±0.08 vs OD450 = 1.55 ± 0.10, P 〈 0.001). The area under the receiver operating character- istic (ROC) curve was 0.87. The sensitivity and specificity for detection of ESCC were 78.0% and 81.0%, respectively, when the OD450 value was greater than 1.65. Although the levels of autoantibodies against MMP-7 were also significantly higher in patients with gastric cancer compared to control samples (OD450 = 1.62± 0.06 vs OD450 = 1.55±0.10, P 〈 0.001), the diagnostic accuracy was less significant than in ESCC patients. The area of ROC curve was 0.75, whereas the sensitivity and specificity were 60.5% and 71.7%, respectively, when the cut-off value of OD450 was set at 1.60. CONCLUSION: Serum autoantibody levels of MMP-7 may be a good diagnostic biomarker for esophageal squamous cell carcinoma,
文摘The aetiology of primary sclerosing cholangitis (PSC) is not known and controversy exists as to whether PSC should be denominated an autoimmune disease. A large number of autoantibodies have been detected in PSC patients,but the specifi city of these antibodies is generally low,and the frequencies vary largely between different studies. The presence of autoantibodies in PSC may be the result of a nonspecifi c dysregulation of the immune system,but the literature in PSC points to the possible presence of specifi c antibody targets in the biliary epithelium and in neutrophil granulocytes. The present review aims to give an overview of the studies of autoantibodies in PSC,with a particular emphasis on the prevalence,clinical relevance and possible pathogenetic importance of each individual marker.
文摘We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patient presented with polydipsia, polyuria, hypergly-cemia, diabetic ketoacidosis, combined with C-peptide secretion defi ciency and positive islet cell autoantibody (ICAb). IFN-α 2b treatment was terminated and in-stead insulin treatment was initiated. Five months after cessation of the recombinant human IFN-α 2b therapy, the patient remained insulin-dependent. Her serum HBV DNA became negative and serum transaminase returned to the normal level after a 10-mo period of IFN therapy. Type 1 DM induced by IFN-α is relatively rare in patients with chronic hepatitis B. We should pay more attention to patients on IFN-α therapy to avoid destruction of pancreatic beta cells. This is the first case report from China.
文摘Autoimmune hepatitis(AIH),initially known as chronic active or active chronic hepatitis(and by various other names),first came under clinical notice in the late 1940s.However,quite likely,chronic active hepatitis(CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver.An earlier(and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E.cell test positivity and emphasized accompanying multisystem features and immunological aberrations.Young women featured prominently in early descriptions of CAH.AIH was first applied in 1965 as a descriptive term.Disease-characteristic autoantibodies were defined from the early 1960s,notably antinuclear antibody(ANA),smooth muscle antibody(SMA) and liver-kidney microsomal(LKM) antibody.These are still widely used diagnostically but their relationship to pathogenesis is still not evident.A liver and disease specific autoantigen has long been searched for but unsuccessfully.Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today.AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8,DR3 haplotype,and also with DR4.Looking forwards,AIH is one of the several enigmatic autoimmune diseases that,despite being(relatively) organ specific,are marked by autoimmune reactivities with non-organ-specific autoantigens.New paradigms are needed to explain the occurrence,expressions and pathogenesis of such diseases.
文摘Although both primary biliary cirrhosis (PBC) and idiopathic thrombocytopenic purpura (ITP) are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the follow-up of PBC in a 74-year- old man. The patient had been diagnosed with PBC 12 years previously, and had received treatment with ursodeoxycholic acid. The platelet count decreased from approximately 60 × 109/L to 8 × 109/L, and the association of decompensated liver cirrhosis (PBC) with ITP was diagnosed. Steroid and immune gamma globulin therapy were successful in increasing the platelet count. Interestingly, human leukocyte antigen genotyping detected the alleles DQB10601 and DRB10803, which are related to both PBC and ITP in Japanese patients. This case suggests common immunogenetic factors might be involved in the development of PBC and ITP.
文摘AIM: To evaluate the prevalence of autoantibodies in chronic hepatitis C virus (HCV)-infected children focusing on thyroid autoimmunity.METHODS: We investigated the prevalence of autoantibodies in 123 chronic HCV-infected children before, during and after monotherapy with interferon-alpha (IFN-α) or combined treatment with interferon-α or peginterferon-α and ribavirin. Besides antibodies against smooth muscle (SMA), nuclei (ANA), and liver/kidney microsomes (1KM), the incidence of antithyroid peroxidase antibodies as well as thyroid function parameters (TSH, FT3 and FT4) were determined.RESULTS: We found that 8% of children had autoantibodies before treatment. During treatment, 18% of children were found positive for at least one autoantibody; 15.5% of children developed pathologic thyroid values during IFN-α treatment compared to only one child before therapy. Six children had to be substituted while developing laboratory signs of hypothyroidism.CONCLUSION: Our data indicate a strong correlation between interferon-α treatment and autoimmune phenomena, notably the emergence of thyroid antibodies. The fact that some children required hormone replacement underlines the need of close monitoring in particularly those who respond to therapy and have to be treated for more than 6 mo.
基金Supported by Estonian Science Foundation grants No. 4437 and 6514.
文摘A1M: To investigate the prevalence of celiac disease (CD) as well as CD marker antibodies and susceptibility HLA-DQ haplotypes in 134 karyotyped Down's syndrome (DS) patients. METHODS: Immunoglobulin A (IgA) and G (IgG) type anti-gliadin antibodies (AGA), IgA type anti-tissue transglutaminase (tTG) antibodies (anti-tTG) with antigen of guinea pig and human source were determined by enzyme-linked immunosorbent assay and endomysium antibodies (EHA) by indirect immunofiuoresence test. HLA-DQA1*0501/DQB1*0201 (DQ2) was revealed by polymerase chain reaction. Celiac disease was diagnosed by revised ESPGHAN criteria. RESULTS: 41% of DS patients had AGA, 6.0% IgA anti-tTG with guinea pig antigen, and 3.0 % [gA EMA (all positive for anti-tTG with human tTG). Subtotal villous atrophy was found in 5 out of 9 DS patients who had agreed to small bowel biopsy. One of them had DQA1*0S01/DQB1*0201 and anti-tTG and EMA i.e. typical for CD markers (this case also fulfilled the ESPGHAN diagnostic criteria), but other four lacked these markers. Three non-biopsied DS patients had also most probably CD because DQA1*0S01/DQB1*0201 and IgA anti-tTG (EMA) were detected. Thus, the prevalence of CD among our DS patients population is 3.0 % (95 % of confidence interval [CI]: 0.1-5.9 %). CONCLUSION: We confirm the increased frequency of CD among DS patients. In addition, we have revealed a subgroup of patients with subtotal villous atrophy but without characteristic for CD immunological and genetic markers. Whether these cases represent CD (with atypical immunopathogenesis) or some other immune enteropathy, requires further investigations.
文摘Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental factors,genetic predisposition and loss of immune tolerance.In recent years,it has become univocally accepted that an inappropriately activated immune response is one of the most important factors in PBC.In this study,the role of autoimmunity in PBC is summarized and a feasible research orientation is recommended.
基金Supported by grants from National Natural Science Foundation of China, No. 30471614 (to DK Qiu) and No.30571730 (to X Ma)Shanghai Leading Academic Discipline Project, No.Y0205 (to X Ma)
文摘To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) in murine experimental autoimmune hepatitis (EAH).METHODS: To induce EAH, the syngeneic S-100 antigen emulsified in complete Freud's adjuvant was injected intraperitoneally into adult male C57BI/6 mice. Liver injury was assessed by serum ALT and liver histology. The expression and activity of p38 MAPK were measured by Western blot and kinase activity assays. In addition, DNA binding activities of nuclear factor kappa B (NF-KB) were analyzed by electrophoretic mobility shift assay. The effects of SB203580, a specific p38 MAPK inhibitor, on liver injuries and expression of proinflammatory cytokines (interferon-y, IL-12, IL-1β and TNF-α) were observed.RESULTS: The activity of p38 MAPK and NF-~:B was increased and reached its peak 14 or 21 d after the first syngeneic S-100 administration. Inhibition of p38 MAPK activation by SB203580 decreased the activation of NF-~:B and the expression of proinflammatory cytokines. Moreover, hepatic injuries were improved significantly after SB203580 administration.
文摘AIM: Celiac disease is characterized by life-long gluten intolerance. Clinical features of patients with celiac disease are variable. Studies about the prevalence of celiac disease in our country are scarce and there is no study on the prevalence of celiac disease in southern Iran. In the current study, clinical, laboratory and histological features of 52 patients with celiac disease were evaluated. METHODS: In a cross sectional study we retrospectively studied the characteristics of 52 celiac patients at Ahwaz JundiShapour University Hospitals (AJSUH) from November 1, 1999 to 1st Sep 2004. Intestinal biopsy and serum antigliadin and anti-endomysium antibodies were used for the diagnosis of patients. Mucosal lesions were classified according to the criteria of Marsh. Antigliadin antibodies were measured with a commercial enzyme-linked immunosorbent assay. Anti-endomysium antibodies were analyzed by indirect immunofluorescence with the use of a section of monkey esophagus. Routine hematological and biochemical analyses and measurement of immunoglobulin levels were undertaken.RESULTS: Male: female ratio was 1.08. The mean + SD patient age was 21 + 4.5 years (range 10-70 years) and the most common symptoms were diarrhea and weight loss (78.8%) followed by fatigue (73.1%), pallor (65.4%), anorexia (40.4%), abdominal distention (32.7%), and failure to thrive (23.1%). Diarrhea and weight loss and fatigue were the most common findings. Iron deficiency anemia was found in 63.2% of patients and this became normal after adoption of a gluten-free diet in all patients. Immunoglobulin A, IgG antigliadin antibodies and IgA anti-endomysium antibodies were found in 33 and 48 cases, 78.8% and 85.4% of patients, respectively. Biopsy of the small intestine revealed that 90.4% of patients had typical lesions according to the Marsh classification. CONCLUSION: Although classical presentation was seen in most of the patients, atypical clinical manifestations of celiac disease should be kept in mind. In particular, patients with uncommon findings, such as short stature, and iron-deficiency anemia, should be screened for celiac disease. Further epidemiological studies in our area in the general population and in high risk groups seem to be indicated.
文摘To compare the clinical and pathological manifestations of patients with antineutrophil cytoplasmic autoantibodies (ANCA) directed against proteinas e 3 (anti PR3) or myeloperoxidase (anti MPO). Methods. One hundred and forty patients with ANCA were detected for anti PR3 a nd anti MPO by ELISA. The clinical features at presentation, histopathological characteristics and outcome of all patients who were tested positive for anti P R3 or anti MPO were analysed.Results. In anti PR3 group (n=21), 16 cases (76.2%) had systemic vasculitis , in which Wegener’s granulomatosis prevailed (13 cases, 61.9%). In anti MPO g roup (n=31), 19 cases (61.3%) were diagnosed as systemic vasculitis and 12 case s (38.7%) as microscopic angiitis. For vasculitic patients with anti PR3 and a nti MPO, the disease duration at diagnosis was 9.6±2.0m and 4.4±0.9m respecti vely, P< 0.05;vasculitis activity index (BVAS) and mean number of affected organ were 22.5±2.1, 5.0±0.4 and 25.1±1.7, 4.8±0.4 respectively, P >0.05;upper r espiratory tract, eye and joint involvements were 11(68.8%), 7(43.8%), 11(68.8 %) and 7(36.8%), 2(10.5%), 5(26.3%) respectively, P< 0.05.Although there was no statistical difference in renal involvement between these two groups, patien ts with serum creatine >500 μmol/L were more commonly seen in anti MPO group t han in anti PR3 group, which were 8(42.1%) and 2(12.5%) respectively, P< 0.05 . Ten relapses were seen in anti PR3 group and only 2 in anti MPO group, but t he acute mortality rate in anti MPO group (5/19, 27.4%) was much higher than t hat in anti PR3 group (1/16, 6.3%). Conclusions. Anti PR3 and anti MPO occurred mainly in systemic vasculitis. A large divergence was seen in the disease spectrum between patients with anti PR 3 and those with anti MPO. In particular, upper respiratory tract, eye and join t involvements, granuloma formation and relapse were more prominent in anti PR3 patients. By contrast, the anti MPO patients had a more acute disease onset, m ore rapid progressive renal involvement and a higher acute mortality rate.
基金Supported by the WHO/TDR, No. 980255 and the Science Commission of Hunan Province, No. 00jzy2115
文摘AIM: To obtain the short peptides mimic antigenic epitopes selected by rat natural antibodies to schistosomes, and to explore their immunoprotection against schistosomiasis in mice.METHODS: Adults worm antigens (AWA) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked transferred immunoblotting methods with normal SD rat sera (NRS). The killing effects on schistosomula with fresh and heat-inactivated sera from SD rats were observed. Then the purified IgG from sera of SD rats was used to biopan a phage random peptide library and 20 randomly selected positive clones were detected by ELISA and 2 of them were sequenced.Sixty female mice were immunized thrice with positive phage clones (0, 2nd, 4th wk). Each mouse was challenged with 40 cercariae, and all mice were killed 42 d after challenge. The worms and the liver eggs were counted. RESULTS: NRS could specifically react to the molecules of 75 000, 47 000, 34 500 and 23 000 of AWA. Sera from SD rats showed that the mortality rate of schistosomula was 76.2%, and when the sera were heat-inactivated in vitro, the mortality rate was decreased to 41.0% after being cultured for 48 h. The specific phages bound to IgG were enriched about 300-folds after three rounds of biopanning. Twenty clones were detected by ELISA, 19 of them bound to the specific IgG of rat sera. Immunization with these epitopes was carried out in mice. Compared with the control groups, the mixture of two mimic peptides could induce 34.9% (P = 0.000) worm reduction and 67.6% (P = 0.000) total liver egg reduction in mice. Two different mimic peptides could respectively induce 31.0% (P = 0.001), 14.5% (P = 0.074) worm reduction and 61.2% (P = 0.000), 35.7% (P = 0.000) total liver egg reduction. The specific antibody could be induced by immunization of the mimic peptides, and the antibody titer in immunized mice reached more than 1:6 400 as detected by ELISA.CONCLUSION: Specific peptides mimic antigenic molecules can be obtained by biopanning the phage random peptide library and a partially protective immunity against schistosome infection can be stimulated by these phage epitopes in mice.
文摘Objective: To investigate the influence of anti-keratin autoantibodies (AK auto Abs) on telom-erase activity of squamous cell carcinoma cultured in vitro and the mechanisms of the inhibitory effects of AK auto Abs on squamous cell carcinoma. Methods: Influence of AK auto Abs on the proliferation of Tca cells was observed by MTT colorimetry. Telomerase activity of cultured Tca cells and human keratinocytes was determined by telomeric repeat amplication protocol-ELISA (TRAP-ELISA) and polyacrylamide gel elec-trophoresis (PAGE). After being treated with AK auto Abs for 36 h at a concentration of 4, 8, 16 mg/L respectively, the changes of telomerase activity of Tea cells were also detected by TRAP-ELISA and PAGE. Results: MTT colorimetric determination showed that the capacity of proliferation of Tca cells correlated negatively with the concentration of AK auto Abs (r= -0. 74, P<0. 01). TRAP-ELISA and PAGE showed that telomerase activity of Tca cells increased significantly compared to that of cultured human keratinocytes (t = 3. 5396, P<0. 01). AK auto Abs at a concentrations of 4, 8, 16 mg/L had significant dose-dependent inhibitory effects on telomerase activity of Tca cells (r= - 0. 8358, P<0. 01). Conclusion: AK auto Abs have a significant dose-dependent inhibitory effect on the proliferation of cultured Tea cells. AK auto Abs inhibit telomerase activity of cultured Tca cells with dose-dependent pattern. It suggests that decrease of telomerase activity may play an important role in the inhibitory effects of AK auto Abs on squamous cell carcinoma.