Association of autoimmune thyroid disease with type 1 diabetes mellitus and its ultrasonic diagnosis and management

As a common hyperglycemic disease,type 1 diabetes mellitus(T1DM)is a complicated disorder that requires a lifelong insulin supply due to the immunemediated destruction of pancreaticβcells.Although it is an organ-specific autoimmune disorder,T1DM is often associated with multiple other autoimmune disorders.The most prevalent concomitant autoimmune disorder occurring in T1DM is autoimmune thyroid disease(AITD),which mainly exhibits two extremes of phenotypes:hyperthyroidism[Graves'disease(GD)]and hypothyroidism[Hashimoto's thyroiditis,(HT)].However,the presence of comorbid AITD may negatively affect metabolic management in T1DM patients and thereby may increase the risk for potential diabetes-related complications.Thus,routine screening of thyroid function has been recommended when T1DM is diagnosed.Here,first,we summarize current knowledge regarding the etiology and pathogenesis mechanisms of both diseases.Subsequently,an updated review of the association between T1DM and AITD is offered.Finally,we provide a relatively detailed review focusing on the application of thyroid ultrasonography in diagnosing and managing HT and GD,suggesting its critical role in the timely and accurate diagnosis of AITD in T1DM.

Enzyme-linked immunosorbent assay of 3 Screen Islet Cell Autoantibody in patients with autoimmune thyroid disease

BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes(T1D).While it has been established that 20%-30%of T1D patients suffer from autoimmune thyroid disease(AITD),there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients.Among commercially available anti-islet autoantibodies,glutamic acid decarboxylase 65 autoantibodies(GADAs)are often the first marker measured in general clinical practice.AIM To investigate the frequency of anti-islet autoantibodies in AITD patients.METHODS Our study involved four hundred ninety-five AITD patients,categorized into three distinct groups:AITD with T1D(n=18),AITD with phenotypic type 2 diabetes(T2D)(n=81),and AITD without diabetes(n=396),and the enzyme-linked immunosorbent assay(ELISA)was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody(3 Screen ICA),GADA,insulinoma-associated antigen-2 autoantibodies(IA-2As),and zinc transporter 8 autoantibodies(ZnT8As)within these groups.RESULTS The frequency of 3 Screen ICA in AITD patients with T1D,T2D,and those without diabetes were 88.9%,6.2%,and 5.1%,respectively,with no significant difference seen between the latter two groups.Notably,the frequency of 3 Screen ICA was 11.1%higher in AITD patients with T1D,1.3%higher in AITD patients with T2D,and 1.1%higher in AITD patients without diabetes compared to GADA,respectively.Furthermore,12.5%,20.0%,and 20.0%of the 3 Screen ICA-positive patients were negative for GADA.Additionally,1.3%of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies.Among the 3 Screen ICA-positive patients,there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes(37.5%vs 5.0%,P<0.05).However,this proportion was similar to that in AITD patients with T2D(20.0%).Nevertheless,there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes(436.8±66.4 vs 308.1±66.4 index).Additionally,no significant difference in 3 Screen ICA titers was observed between Graves’disease and Hashimoto’s thyroiditis in any of the groups.CONCLUSION Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D.Thus,3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.

Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases:A case report

BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.

Selenium Supplementation Alleviates Autoimmune Thyroiditis by Regulating Expression of Th1/Th2 Cytokines

Selenium （Se） is an essential trace element. Autoimmune thyroid diseases （AITD） are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the effects of Se on the cytokines in AITD are still unclear. So we researched the role of Selenium （Se） and Thl/Th2 cytokine productions in the pathogenesis of autoimmune thyroid diseases （AITD）.

IMMUNOHISTOCHEMICAL STUDY OF ESTROGEN AND PROGESTERONE RECEPTOR IN THYROID TISSUES OF AUTOIMMUNE THYROID DISEASE

Estrogen receptor(ER) and progesterone receptor (PgR) in core-needle biopsied thyroidtissues of 30 cases of autoimmune thyroid disease and 2 cases of simple gotter were measured usingenzyme-linked histochemical technique. The results showed that the frequences of presence of ER inGraves' disease (GD) and Hashimoto's thyroditis(HT) were 50% (9/18) and 58. 3K (7/12) respectively ; and those of PgR were 11. 1 % (2/18) in GD, 16. 2% (2/7) in HT. Both ER and PgR werenegative in simple gotter. This study demonstrated that the content of ER in thyroid tissues of autoimmune thyroid disease was relatively high, suggesting that estrogen may play a role in the development of the disease.

Effect of IL-10 gene transmission on the PTg-stimulated splenocytes proliferation and Th1 cytokines production from experimental autoimminue thyroiditis rats

To investigate the effects of gene therapy with IL-10 on PTg-induced proliferation of splenocytes and Thl cytokine production from PTg-stimulated splenocytes. Methods： EAT rats were divided into four groups ：group A （PBS＋PLL） , group B （pORF＋PLL）, group C （pORFmIL10＋PLL）, and group D （pORFmIL10＋ MEM）. The substances mixed with lipofectamine were injected into the thyroid tissues of rats on the 18th dday after immunization. The rats were sacrificed at the 8th week. In vitro proliferative responses to ConA and different concentration of PTg were measured by culturing 4 ×105 splenocytes pulsed with 18.5KBq of [^3H] thymidine for the final 12h and then harvested for liquid scintillation counting. In vitro splenocytes were cultured with PTg （25 mg/L）. Thl cytokine IFN-γ,TNF-α and IL-2 were detected by ELISA. Results： The proliferative response to PTg was suppressed in group C, compared with that of group A and B （P 〈 0.05）. The levels of IFN-γ,TNF-αand IL-2 in the supernatant of PTg-stimulated splenocytes were 3548.25±779.47 pg/ml, 27.66±10.50 pg/ml and 3617.73±609.15 pg/ml, respectively, which were much lower in group C than those in group A and B（P 〈 0.01, P 〈 0.05, P 〈 0.001, respectively）. Conclusion： IL- 10 gene transmission in thyroid tissues could inhibit PTg specific proliferation of splenocytes from EAT rats and the secretion 6f Th1 cytokines from PTg-stimulated splenocytes.

Intervention and immune regulation of Fuzheng Xiaoying Decoction on experimental autoimmune thyroiditis model rats

Objective:To investigate the effect of Fuzheng Xiaoying Decoction on experimental autoimmune thyroiditis(EAT)model rats and explore its possible mechanism of immune regulation.Methods:Among the 40 female SD rats,10 were randomly selected as the blank group,and the rest were immunized with pig thyroglobulin and Freund's adjuvant combined with high iodine feeding to make the EAT model.After the model was established,they were randomly divided into three groups:the model group,the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group,which were continuously gavaged for 2 months.The anti thyroid autoantibodies,thyroid function,IL-38 and Th17/Treg distribution were measured.The pathological changes of thyroid tissue were observed by HE staining.Results:Compared with the blank group,the levels of TPOAb and TGAb in the model group were significantly higher(P<0.05).Lymphocyte infiltration was seen in the thyroid tissue of the model group,and also the thyroid follicles were partially destroyed,the shape was irregular,and the colloid distribution was uneven,indicating that the modeling was successful.Compared with the model group,the levels of TPOAb and TGAb in the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group decreased significantly(P<0.05).And the Fuzheng Xiaoying Decoction group had more significant improvement in thyroid follicle destruction and lymphocyte infiltration than the selenium yeast tablet group(P<0.05).Compared with the blank group,the levels of T3,T4,FT3 and FT4 in the model group increased,the level of IL-38 decreased,the proportion of Th17 increased,and the ratio of Th17/Treg increased(P<0.05).Compared with the model group,T4 level decreased,IL-38 level increased in the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group(P<0.05).But there was no statistically significant difference in the reduction of Th17 proportion and Th17/Treg ratio between the above two groups and the model group(P>0.05).There was no significant difference in Treg ratio among the groups.Conclusion:Fuzheng Xiaoying Decoction can significantly reduce the level of anti thyroid autoantibodies in EAT rats by regulating the immunity of EAT rats,and improve the follicular destruction and lymphocyte infiltration of thyroid tissue in rats.

STUDY ON THE HETEROGENEITY OF TSH RECEPTOR ANTIBODIES IN THE PATHOGENESIS OF AUTOIMMUNE THYROID DISEASE

Objective To investigate the heterogeneity of TSH receptor antibodies ofpatients with autoimmune thyroid disease (AITD). Methods Six patients with heterogeneous TSH receptor antibodies were selected. The EBV-transformed B cell clones producing monoclonal anti-thyrotropin receptor antibodies were established from those selected patients. Results 125I-TSHbinding inhibiting immunoglobulin (TBII) values of the 6 patients ranged from 51 % to 89%. Thyroid stimulating antibody (TSAb) existed in patients No. 1,2, 4, 5 and 6 while only patients No. 1,2 and 3 had thyroid stimulation-blocking antibody (TSBAb ). After EBV-transformation of the peripheral B lymphocytes from those patients, we isolated and characterized 5 Bcell clones prepucing the TBII from patient No. 3 and 4 B cell clones prepucing TSAb from patient No. 6. Conclusion Autoantibodies against the us receptor are polyclonal and consist of heterogeneous populations with both stimulatory and inhibitory effects.

Epidemiological and Clinical Aspects of Autoimmune Dysthyroidism in Internal Medicine at Aristide Le Dantec Hospital

Introduction: Autoimmune thyroiditis is relatively common in medicine. However, comprehensive studies are few in number, especially in Africa and particularly in Senegal. The aim of this study was therefore to determine the epidemiological, clinical, profile of Autoimmune Thyroid Diseases (OITD). Materials and Methods: This was a retrospective descriptive study from 2016 to 2019 of the records of patients who consulted or were hospitalised for autoimmune dysthyroidism in the internal medicine department of the Aristide Le Dantec Hospital. During this period, 1227 new consultations were recorded;they concerned three specialized consultations including endocrinology. The autoimmune origin was confirmed in 159 patients, i.e. in 45.69% of cases the AIDM then 12.96% of all consultations. The autoimmune origin was established on clinical, biological and immunological grounds. The data were collected from the medical records of the patients and recorded on a pre-established individual survey sheet taking into account the objectives of the study. The data collected was entered into the Sphinx V5 software on an established form. The analysis was carried out with the following software: Excel 2010 and Epi info 7.2. Results: Among this dysthyroidism, 159 patients had a confirmed autoimmune thyroid disease. On all new consultations, OITD represented 12.96% of internal medicine consultations. The sex ratio M/F was 0.18. The majority of our patients (57.86%) were aged between 25 and 44 years with extremes ranging from 11 to 63 years. In Graves’ disease, the notion of an irritative spine was found in 60.27% of cases. Signs of thyrotoxicosis were present in 92.7% of cases. There was a goiter in 81.1% of cases with a vascular character in 76.47% of cases. Anti-THR antibodies were positive in 96.15% of cases. Complications were noted in 9 patients (6.5%) such as cardiothyreosis in 8 patients (5.7%) and malignant orbitopathy noted in 1 patient (0.8%). In Hashimoto’s thyroiditis, signs of hypometabolism were evident in 87.50% of patients. Anti-TPO antibodies were positive in all patients. All patients had received thyroid hormone supplementation. Thyroid autoimmune disease was associated with other autoimmune diseases in 6.2% of cases. Conclusion: Autoimmune thyroiditis is common in our daily practice in Senegal;it is dominated by Grave’s disease. Hypothyroidism was the most common manifestation of Hashimoto’s thyroiditis. The inaccessibility of antithyroid antibody testing is an obstacle to the diagnosis and management of these conditions.

The Role of Vitamin D on Thyroid Antibodies in Patients with Chronic Autoimmune Thyroiditis

Vitamin D deficiency is a global problem,which has taken the form of a pandemic.Existing data indicate that vitamin D is not only a nutrient.It has also a hormone-specific activity.Vitamin D is characterized by anti-inflammatory and immunomodulatory properties.Chronic autoimmune thyroiditis is a disease of autoimmune genesis,in which lymphocytic infiltration gradually destroys thyroid tissue.There are some evidences about vitamin D deficiency and the development of chronic autoimmune thyroiditis.The article has reviewed the current literature about the impact and the benefits of vitamin D on thyroid antibodies levels.

Multi-organ IgG4-related disease continues to mislead clinicians: A case report and literature review

BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a multisystemic mass forming immune-mediated disease that affects almost every organ and is a diagnostic challenge for every clinician.There is a lack of adequate epidemiological data worldwide,and evidence-based treatment recommendations are not yet established.We report the first case of IgG4-RD from Lithuania and the Baltic Sea region presented with thyroiditis,orbital myositis,orbitopathy,uveitis,scleritis,sialadenitis,autoimmune pancreatitis and prostatitis.CASE SUMMARY A 54-year-old Caucasian male was admitted to our tertiary Centre complaining of severe weight loss,diarrhoea,abdominal pain,salivary gland swelling,sicca symptoms and diplopia.On examination,bilateral palpable masses in the projection of major salivary glands,severe protrusion of the left eyeball and cachexia were noted.The patient was previously diagnosed with autoimmune thyroiditis and endocrine ophthalmopathy.The magnetic resonance imaging(MRI)of the head revealed enlarged extraocular muscles indicating orbital myositis.The biopsy from the salivary gland mass indicated sialadenitis.Abdominal MRI showed signs of autoimmune pancreatitis,and a serological test revealed the elevated serum IgG4 concentration.The patient was then diagnosed with IgG4-RD and successfully treated with prednisolone.There was a significant clinical,serological and radiological improvement after one month of treatment and no signs of relapse within twenty months.However,it took almost 18 years and the efforts of eight different medical specialists to establish the correct diagnosis.CONCLUSION A comprehensive approach to the patient is essential to improving the recognition of rare immune system conditions,such as IgG4-RD.

THE CLINICAL SIGNIFICANCE OF TSAb IN GRAVES' DISEASE

TSAb and TSBAb both were measured in i63 patients with Graves' disease(GD) and 31 Autoimmune Thyroiditis(AIT) individually and simultaneously. The TSAb activities and positive percentage in active and relapse GD groups were higher than those in the normal control and euthyroidgroups; no significant difference was found between the active GD and relapse GD groups. TSAb were positive in one of 31 Patients with hypothyroidism due to AIT. TSBAb were positive in GD patients after treatment who became patients with hypothyroidism and patients with bypothyroidism dueto AIT, being 30. 0% and 35.5% respectively. TSAb and TSBAb were measured simultaneously in 35GD patients with different thyroid function status, and 4 PatientS with hypothyroidism due to AIT.We found that two patients with GD who were euthyroid during treatment with ATD and one patient with active GD had TSAb and TSBAb coexisting in circulation. we would postulate that perhaps only one kind of preponderant autoantibody activity could be detected and those nonpreponderant autoantibodies might be very difficultly found, when the patients were in a certain stable thyroid function saute.

Vitamin D and autoimmune thyroid diseases

The role of vitamin D as an immune modulator has been emphasized in recent years,and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemic lupus erythematosus.Vitamin D mediates its effect though binding to vitamin D receptor(VDR),and activation of VDR-responsive genes.While VDR gene polymorphism was found to associate with autoimmune thyroid diseases(AITDs),few studies examined levels of vitamin D in these patients and those that did yielded conflicting results.We therefore undertook to evaluate the levels of vitamin D in patients with AITDs compared to patients with non-AITDs and healthy controls.Serum vitamin D(25-OH)levels were measured in 50 patients with AITDs,42 patients with non-AITDs and 98 healthy subjects,utilizing the LIAISON chemiluminescence immunoassay(DiaSorin,Saluggia,Italy).VitaminD deficiency was designated at levels lower than 10 ng/ml.Antithyroid antibodies,thyroid functions and demographic parameters were evaluated in all patients.The prevalence of vitamin D deficiency was significantly higher in patients with AITDs compared with healthy individuals(72% versus 30.6%;P<0.001),as well as in patients with Hashimoto’s thyroiditis compared to patients with non-AITDs(79% versus 52%;P<0.05).Vitamin D deficiency also correlated to the presence of antithyroid antibodies(P=0.01)and abnormal thyroid function tests(P=0.059).Significantly low levels of vitamin D were documented in patients with AITDs that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests,suggesting the involvement of vitamin D in the pathogenesis of AITDs and the advisability of supplementation.

Xiaoyin Recipe(消银方) for Psoriasis Induces a Th1/Th2 Balance Drift Toward Th2 in Peripheral Blood Mononuclear Cells of Experimental Autoimmune Thyroiditis Rats

Objective： To explore the regulatory mechanism of Xiaoyin Recipe （消银方） on the T helper 1/ T helper 2 （Th1/Th2） immune balance. Methods： Thirty-six experimental animals were divided into three groups, 12 rats in each group： blank control group （B group）, negative control group （N group）, and Xiaoyin Recipe treatment group （T group）. The latter two groups received immunization of experimental autoimmune thyroiditis （EAT）, and T group were treated with Xiaoyin Recipe for a month. Then, the expression of Th1-Th2-related genes in peripheral blood mononuclear cells （PBMCs） were screened with Oligo GEArray Rat Thl-Th2-Th3 Microarray. The expressions of tumor necrosis factor- α （TNF- α）, interleukin-10 （IL-10）, T-box expressed in T-cells （T-bet）, and GATA-binding protein-3 （GATA-3） were detected by real-time polymerase chain reaction （RT-PCR）. Results： Gene array screening showed that compared to N group, in T group after Xiaoyin Recipe treatment, 3 genes were upregulated in EAT rats, including interleukin-27 receptor alpha （IL-27roL）, glomulin （GImn）, and GATA-3, while 38 genes were downregulated, such as CD28, IL-18, signal transducer, and activator of transcription 1 （STAT1）, T-bet, TNF receptor superfamily member 4 （TNFRSF4）, TNF ligand superfamily member 5 （TNFSF5）, and TNF receptor superfamily member 5 （TNFRSF5）. While RT-PCR showed that there was an increased level of TNF-α mRNA （P〈0.01）, an elevated ratio of T-bet/GATA-3, and a decreased level of IL-10 mRNA in PBMC of N and T group compared to B group （P〈0.01）; and after treatment with Xiaoyin Recipe, IL-10 mRNA level increased （P〈0.01）, while TNF-α mRNA level and T-bet/GATA-3 ratio decreased in T group compared to N group （P〈0.01）. Conclusion： Xiaoyin Recipe for psoriasis could induce a Thl/Th2 balance drift toward Th2 in PBMC of EAT rats and thus improve the conditions.

CMV-hFasL transgenic mice prevent from experimental autoimmune thyroiditis

Background Previous studies showed that the role of Fas ligand (FasL) is not consistent in the pathogenesis of autoimmune thyroiditis. This study was designed to investigate the effects of FasL on the pathogenesis of experimental autoimmune thyroiditis (EAT) using CMV-human FasL (hFasL) transgenic mice. Methods Transgenic mice ubiquitously expressing hFasL were used as an animal model of EAT by injection of porcine thyroglobulin (pTg). Expression of hFasL was detected by RT-PCR and Western blot. The activity of hFasL transgenic thyrocytes killing Jurket cells was determined. CMV-hFasL transgenic mice and wild type (WT) mice were immunized with pTg and killed 28 days later to evaluate the lymphocytic infiltration of their thyroids. The number of CD4+ and CD8+ lymphocytes from the spleen was detected using FACS. The serum interferon-γ (IFN-γ) concentration was measured by ELISA. Results hFasL expression in the thyroid of CMV-hFasL transgenic mice was confirmed. After co-incubation of Jurket thymocytes with thyroid tissues of CMV-hFasL transgenic mice, the percentage of apoptotic cells in the CMV-hFasL transgenic thyroid group was significantly higher than that of the control WT thyroid group ［(23.4±4.3)% vs (6.6±2.5)%, P<0.01］. On day 28 after immunization with pTg, the infiltration index of lymphocytes in thyroids of the CMV-hFasL transgenic mice was significantly lower than that of the WT mice ［(1.0±0.5) vs (2.1±0.7), P<0.001］. Moreover, the number of CD4+ and CD8+ lymphocytes of the spleen and serum IFN-γ concentration were significantly decreased in the CMV-hFasL transgenic mice. Conclusions FasL plays an important role in the pathogenesis of autoimmune thyroiditis. Transgenic mice ubiquitously expressing hFasL may strongly inhibit lymphocytic infiltration of the thyroid of EAT and ameliorate the course of this disease.

Herb-partitioned moxibustion regulated the miRNA expression profile in the thyroid tissues of rats with experimental autoimmune thyroiditis

OBJECTIVE:To observe the effect of herb-partitioned moxibustion(HPM)on the miRNA expression profile of thyroid tissue in experimental autoimmune thyroiditis(EAT)rats.METHODS:Rats were randomly divided into normal control(NC)group,EAT model(EAT)group,HPM group and western medicine(Med)group.EAT model rats were prepared by a combined immunization with complete and incomplete Freund’s adjuvant emulsified with porcine thyroglobulin and iodine.Rats in the HPM group were treated with HPM,while rats in the Med group were treated with levothyrocine(1μg/2 m L)by gavage.HE staining was used to observe the pathological morphological changes of thyroid tissue,ELISAs was uaed to detect the serum concentrations of TGAb,TPOAb,FT3,FT4,TSH.We then performed high-throughput mi RNA sequencing to analyse the mi RNA expression profiles in the thyroid tissues,followed by a bioinformatics analysis.RT-q PCR was used to verify the identified differentially expressed mi RNAs.RESULTS:HPM improved the thyroid tissue morphology and reduced serum TPOAb,TGAb,TSH concentration in EAT rats(P<0.05),but with no obvious effect on FT3 and FT4 concentration.While the TSH,FT3 and FT4 concentration was significantly changed in the Med group(P<0.01 or P<0.05)compared with that of EAT group.Sequencing results showed that a total of 17 mi RNAs were upregulated,and 4 were downregulated in the EAT rats,in which the expression levels of mi R-346 and mi R-331-5 p were reversed by HPM.The target genes of the mi RNAs that regulated by HPM wereassociated with a variety of immune factors and immune signals.RT-q PCR verification showed that the expression of mi RNA-346 and mi RNA-331-5 p was consistent with the sequencing results.CONCLUSIONS:HPM could regulate the the expression of mi RNA-346 and mi RNA-331-5 p,then act on their target genes to immune and inflammation-related pathways,which may be one of the mechanisms of HPM on EAT rats.

Antigen Processing by Autoreactive B Cells Promotes Determinant Spreading

Acute primary immune responses tend to focus on few immunodominant determinants using a very limited number of T cell clones for expansion, whereas chronic inflammatory responses generally recruit a large number of different T cell clones to attack a broader range of determinants of the invading pathogens or the inflamed tissues. In T cell-mediated organ-specific autoimmune disease, a transition from the acute to the chronic phase contributes to pathogenesis, and the broadening process is called determinant spreading. The cellular components catalyzing the spreading reaction are not identified. It has been suggested that autoreactive B cells may play a central role in diversifying autoreactive T cell responses, possibly through affecting antigen processing and presentation. The clonal identity and diversity of the B cells and antibodies seem critical in regulating T cell activity and subsequent tissue damage or repair. Here, we use two autoimmune animal models, experimental autoimmune thyroiditis （EAT） and type 1 diabetes （T1D）, to discuss how autoreactive B cells or antibodies alter the processing and presentation of autoantigens to regulate specific T cell response. Cellular ＆ Molecular Immunology. 2005;2（3）：169-175.