Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

Anti-nuclear matrix protein 2+ juvenile dermatomyositis with severe skin ulcer and infection: A case report and literature review

BACKGROUND Juvenile dermatomyositis(JDM)is an idiopathic inflammatory myopathy that occurs in childhood.It is characterized by muscle weakness and a characteristic rash.Previous literature reports have rarely described JDM with severe skin ulcers and infections.CASE SUMMARY Herein,we describe a case of a 2-year-old female patient who suffered from JDM,whose myositis-specific autoantibodies were positive for anti-nuclear matrix protein 2 antibody,with progressively worsening skin ulcers and severe infections.The patient was treated with glucocorticoids and various immunosuppressants.Nevertheless,further progression of the disease and the combination of primary disease and severe infection in the later period were fatal.CONCLUSION In children,anti-nuclear matrix protein 2+JDM combined with skin ulcers often indicates severe disease.In such cases,personalized treatment for the primary disease and infection prevention and control are essential.

A candidate targeting molecule of insulin-like growth factor-Ⅰ receptor for gastrointestinal cancers

Advances in molecular research in cancer have brought new therapeutic strategies into clinical usage.One new group of targets is tyrosine kinase receptors,which can be treated by several strategies,including small molecule tyrosine kinase inhibitors(TKIs) and monoclonal antibodies(mAbs).Aberrant activation of growth factors/receptors and their signal pathways are required for malignant transformation and progression in gastrointestinal(GI) carcinomas.The concept of targeting specif ic carcinogenic receptors has been validated by successful clinical application of many new drugs.Type I insulin-like growth factor(IGF) receptor(IGF-IR) signaling potently stimulates tumor progression and cellular differentiation,and is a promising new molecular target in human malignancies.In this review,we focus on this promising therapeutic target,IGF-IR.The IGF/IGF-IR axis is an important modifier of tumor cell proliferation,survival,growth,and treatment sensitivity in many malignant diseases,including human GI cancers.Preclinical studies demonstrated that downregulation of IGF-IR signals reversed the neoplastic phenotype and sensitized cells to anticancer treatments.These results were mainly obtained through our strategy of adenoviruses expressing dominant negative IGF-IR(IGF-IR/dn) against gastrointestinal cancers,including esophagus,stomach,colon,and pancreas.We also summarize a variety of strategies to interrupt the IGFs/IGF-IR axis and their preclinical experiences.Several mAbs and TKIs targeting IGF-IR have entered clinical trials,and early results have suggested that these agents have generally acceptable safety profiles as single agents.We summarize the advantages and disadvantages of each strategy and discuss the merits/demerits of dual targeting of IGF-IR and other growth factor receptors,including Her2 and the insulin receptor,as well as other alternatives and possible drug combinations.Thus,IGF-IR might be a candidate for a molecular therapeutic target in human GI carcinomas.

Autoimmune liver disease-related autoantibodies in patients with biliary atresia

AIM To investigate the prevalence and clinical significance of autoimmune liver disease(ALD)-related autoantibodies in patients with biliary atresia(BA).METHODS Sera of 124 BA patients and 140 age-matched non-BA controls were assayed for detection of the following autoantibodies: ALD profile and specific anti-nuclear antibodies(ANAs), by line-blot assay; ANA and antineutrophil cytoplasmic antibody(ANCA), by indirect immunofluorescence assay; specific ANCAs and antiM2-3 E, by enzyme linked immunosorbent assay. Associations of these autoantibodies with the clinical features of BA(i.e., cytomegalovirus infection, degree of liver fibrosis, and short-term prognosis of Kasai procedure) were evaluated by Spearman's correlation coefficient.RESULTS The overall positive rate of serum autoantibodies in preoperative BA patients was 56.5%. ALD profile assay showed that the positive reaction to primary biliary cholangitis-related autoantibodies in BA patients was higher than that to autoimmune hepatitis-related autoantibodies. Among these autoantibodies, anti-BPO was detected more frequently in the BA patients than in the controls(14.8% vs 2.2%, P < 0.05). Accordingly, 32(25.8%) of the 124 BA patients also showed a high positive reaction for anti-M2-3 E. By comparison, the controls had a remarkably lower frequency of anti-M2-3 E(P < 0.05), with 6/92(8.6%) of patients with other liver diseases and 2/48(4.2%) of healthy controls. The prevalence of ANA in BA patients was 11.3%, which was higher than that in disease controls(3.3%, P < 0.05), but the reactivity to specific ANAs was only 8.2%. The prevalence of ANCAs(ANCA or specific ANCAs) in BA patients was also remarkably higher than that in the healthy controls(37.9% vs 6.3%, P < 0.05), but showed no difference from that in patients with other cholestasis. ANCA positivity was closely associated with the occurrence of postoperative cholangitis(r = 0.61, P < 0.05), whereas none of the autoantibodies showed a correlation to cytomegalovirus infection or the stages of liver fibrosis.CONCLUSION High prevalence of autoantibodies in the BA developmental process strongly reveals the autoimmunemediated pathogenesis. Serological ANCA positivity may be a useful predictive biomarker of postoperative cholangitis.

Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

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+ 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.

Detection of autoantibodies in the serum of primary hepatocarcinoma patients

Objective: To study the significance of detecting au-toantibodies in primary hepatocarcinoma(PHC) pa-tients.Methods: Autoantibodies were detected by indirect im-munofluorescence assay. Antigens and antibodies ofHBV were determined by enzymeimmune assay. Antibodyto HCV IgG was detected by enzyme-linked immunoab-sorbent assay.Results: The positive rate of autoantibody was 27.3%(38/139) in 139 PHC patients. The main type of au-toantibodies in PHC was anti-nuclear antibody (36/38, 94.7%); others included anti-smooth muscle anti-body(2/38, 5.3% ), anti-mitochondria antibody(1/38, 2.6%), anti-midbody antibody (1/38, 2.6%), andanti-liver cell membrane antibody(2/38, 5.3%).Conclusions: Detecting autoantibodies in PHC patientsis of significance in studying the mechanism of au-toimmune reaction and etiology in PHC. The diversityof autoantibodies might result from a wide variety ofetiological factors involved in PHC development, andfrom a wide variety of overexpressed or mutated pro-teins involved in repeated cycles of necrosis and regen-eration in hepatocarcinoma development.

Systemic autoimmune abnormalities complicated by cytomegalovirus-induced hemophagocytic lymphohistiocytosis:A case report

BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a rare but life-threatening disorder,characterized by a hyperimmune response.The mortality is high despite progress being made in the diagnosis and treatment of the disease.HLH is traditionally divided into primary(familial or genetic)and secondary(reactive)according to the etiology.Secondary HLH(sHLH),more common in adults,is often associated with underlying conditions including severe infections,malignancies,autoimmune diseases,or other etiologies.CASE SUMMARY The case involves a 31-year-old woman,presented with a high persistent fever,rash,and splenomegaly.She met the diagnostic criteria of the HLH-2004 guideline and thus was diagnosed with HLH,with positive anti-nuclear antibody(ANA)and positive cytomegalovirus(CMV)-DNA.The patient responded well to a combination of immunomodulatory,chemotherapy,and supportive treatments.When her PCR evaluation for CMV turned negative,her serum ferritin also dropped significantly.Her clinical symptoms improved dramatically,and except for ANA,the abnormal laboratory findings associated with HLH returned to normal.Our previous study has shown that the median overall survival of HLH patients is only 6 mo;however,our patient has been cured and has not presented with any relapse of the disease for 6 years.CONCLUSION This case emphasizes that thorough early removal of the CMV infection is significant for the prognosis of this HLH patient.

Global analysis of a reaction-diffusion blood-stage malaria model with immune response

Malaria is one of the most dangerous diseases that threatens people's lives around the world.In this paper,we study a reaction-difusion model for the within-host dynamics of malaria infection with an antibody immune response.The model is given by a system of partial differential equations(PDEs)to describe the blood-stage of malaria life cycle.It addresses the interactions between uninfected red blood cells,antibodies,and three types of infected red blood cells,namely ringinfected red blood cells,trophozoite-infected red blood cells and schizont-infected red blood cells.Moreover,the model contains a parameter to measure the efficacy of isoleucinc starvation and its effect on the growth of malaria parasites.We show the basic properties of the model.We compute all equilibria and derive the thresholds from the conditions of existence of malaria equilibrium points.We prove the global stability of all equilibrium points based on choosing suitable Lyapunov functionals.We use the characteristic equations to verify the local instability of equilibrium points.We finally execute numerical simulations to validate the theoretical results and highlight some important observations.The results indicate that isoleucine starvation can have a critical impact on the stability of equilibrium points.When the efficacy of isoleucine starvation is high,it switchcs the system from the infection state to the malaria-free state.The presence of an antibody immune response does not lead to the elimination of malaria infection,but it suppresses the growth of malaria parasites and increases the amount of healthy red blood cells.