B cell activated co-receptor plays important roles in linkage of innate and acquired humoral immune responses. CD21 molecule in the co-receptor complex is a receptor for C3dg and CD19 molecule enhances BCR signal transduction. CD21 also expresses on the surface of follicular dendritic cells, which mediates the long-term maintenance of antigens and is indispensable for maintaining the memory of B cells. B cell activated co-receptor also has an effect on the negative selection of B cells reactive to autoantigens.
Animals ; Antigens, CD19 ; immunology ; Autoantigens ; immunology ; B-Lymphocytes ; immunology ; Humans ; Receptors, Complement 3d ; immunology ; Receptors, Immunologic

BACKGROUNDPatients with systemic lupus erythematosus often have various autoantibodies. The relationship between these antibodies is still poorly understood. The aim of the present study was to observe the anti-SSB antibody and anti-dsDNA antibody production profiles following immunization with synthetic SSB peptide alone, DNA alone or co-immunization with these two antigens.

METHODSSSB 214 - 225 aa peptide was synthesized by organic chemistry solid-phase peptide synthesis. Rabbits were immunized with the following antigens: synthetic SSB peptide linked with keyhole limpet hemocyanin (KLH), DNA, SSB plus dsDNA, KLH and PBS. Antibodies were measured by ELISA. Histopathology and direct immufluorescence assays were also applied.

RESULTSAnti-SSB and anti-dsDNA antibodies were produced following immunization with SSB peptide and DNA respectively. The level of SSB antibody in the co-immunization group was higher than that of the SSB peptide immunization group. The level of anti-dsDNA antibody in the co-immunization group was, however, lower than that in the DNA immunization group. Meanwhile, the level of anti-SSB antibody was higher than that of anti-DNA antibody in the co-immunization group. No morphological or immunological abnormalities were found in the heart, liver, kidney, spleen or skin tissues.

CONCLUSIONInhibition of anti-dsDNA-antibody was induced by co-immunization with synthesized SSB peptide and DNA, which might explain, at least partly, the mild disease in some LE subsets associated with SSB antibody.

Animals ; Antibodies, Antinuclear ; biosynthesis ; Autoantigens ; immunology ; DNA ; immunology ; Fluorescent Antibody Technique, Direct ; Immunization ; Rabbits ; Ribonucleoproteins ; immunology

OBJECTIVESTo establish a primary biliary cirrhosis (PBC) model by AMAM2 autoantigen injection into C57BL/6 mice.

METHODSMice of the model group were immunized intraperitonealy with 200 microl of purified recombinant AMAM2 autoantigen in complete Freund's adjuvant (CFA). Mice immunized with bovine serum albumin and CFA in the same way were used as negative controls. Sixty-six weeks later, mice were sacrificed and their sera were collected. Sera samples were assayed for AMAM2 autoantibody, alkaline phosphatase (ALP), ALT and total bilirubin (TBil). Their liver, stomach, muscle and kidney tissues were sectioned and stained using HE to observe the pathological changes.

RESULTSAntibodies to AMAM2 autoantigen were readily induced in the model group. The mice in the model group had no significant changes in the level of serum ALT and TBil but had an obvious increase of ALP (P<0.05). The stomach, muscle and kidney tissues showed no evident damage while the livers had obvious pathological changes, including bile duct degeneration or proliferation, and mononuclear cell infiltration.

CONCLUSIONThe AMAM2 autoantigen-induced PBC animal model was successfully established in C57BL/6 mice in our experiment and its characteristic biochemical and pathology are quite similar to that in the early stage of human PBC. This model may provide a useful experimental approach for further study of the pathogenesis and clinical treatment of human PBC.

Animals ; Autoantigens ; immunology ; Disease Models, Animal ; Liver Cirrhosis, Biliary ; etiology ; Mice ; Mice, Inbred C57BL ; Mitochondria ; immunology

OBJECTIVETo identify the candidate auto-antigen of rheumatic heart disease as a molecular marker for this disease.

METHODSThe total RNA of the heart tissue of patients with rheumatic heart disease was extracted and reverse-transcribed into long cDNA to construct the phage expression library. The library was screened using the serum from patients with active rheumatic fever, and the positive clone was identified and analyzed by bioinformatics and expressed in vitro. The expressed products were evaluated with Western blotting and its cross-reactivity was assessed.

RESULTSThe phage expression library of the heart tissue of patients with rheumatic heart disease was constructed, with the titer of the primary library of 3.3×10(6) pfu/ml, recombinant rate of 99%, and 81% of the inserted segments were larger than 1 kb. An auto-antigen RHDAG1 was identified by screening, which was homologous to keratin 18. RHDAG1 was detected in the serum of patients with active rheumatic fever and of those with rheumatic heart disease, but not in the serum of healthy subjects.

CONCLUSIONPhage display library can be an effective strategy to screen the auto-antigens of rheumatic heart disease. The auto-antigen RHDAG1 can be a candidate molecular biomarker of rheumatic heart disease and/or rheumatic fever.

Autoantibodies ; blood ; immunology ; Autoantigens ; immunology ; isolation & purification ; Autoimmune Diseases ; blood ; immunology ; Humans ; Peptide Library ; Rheumatic Heart Disease ; immunology

OBJECTIVETo evaluate the utility of zinc transporter-8 (ZnT8) in the improvement of type 1 diabetes mellitus (T1DM) diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in T1DM.

DATA SOURCESA search was conducted within the medical database PubMed for relevant articles published from 2001 to 2015. The search terms are as follows: "ZnT8," "type 1 diabetes," "latent autoimmune diabetes in adults," "type 2 diabetes," "islet autoantibodies," "zinc supplement," "T cells," "β cell," "immune therapy." We also searched the reference lists of selected articles.

STUDY SELECTIONEnglish-language original articles and critical reviews concerning ZnT8 and the clinical applications of islet autoantibodies in diabetes were reviewed.

RESULTSThe basic function of ZnT8 is maintaining intracellular zinc homeostasis, which modulates the process of insulin biosynthesis, storage, and secretion. Autoantibodies against ZnT8 (ZnT8A) and ZnT8-specific T cells are the reliable biomarkers for the identification, stratification, and characterization of T1DM. Additionally, the results from the animal models and clinical trials have shown that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific immunotherapy as an alternative for T1DM therapy.

CONCLUSIONSZnT8 is a novel islet autoantigen with a widely potential for clinical applications in T1DM. However, before the large-scale clinical applications, there are still many problems to be solved.

Animals ; Autoantibodies ; immunology ; Autoantigens ; immunology ; Cation Transport Proteins ; immunology ; metabolism ; Diabetes Mellitus, Type 1 ; immunology ; metabolism ; Humans

OBJECTIVETo investigate the main components of inner ear antigens inducing autoimmune Meniere's disease (AIMD) in guinea pigs.

METHODSThe guinea pigs were immunized with isologous crude inner ear antigens (ICIEAg). Then, the hearing function was measured with auditory brainstem response (ABR), the vestibular function was measured with electronystagmography (including spontaneous nystagmus and caloric test), and inner ear histopathological changes were observed by inner ear celloidin section with haematoxylin-eosin staining and observed under light microscope. According to these results, the AIMD-model animals from non-AIMD-model ones were distinguished. The special antibodies against ICIEAg in sera were measured with ELISA. The antigen-antibody reactions against different components of ICIEAg were detected by Western blotting with sera of AIMD and non-AIMD guinea pigs respectively. Then, we analysed the contrast between them and found the main components of the ICIEAg that were positive reaction in AIMD guinea pigs and negative reaction in non-AIMD guinea pigs.

RESULTSThe result of ELISA demonstrated that the sera of both the AIMD and non-AIMD guniea pigs contained the special antibodies against ICIEAg after immunized with ICIEAg. The difference of the amount of antibody against ICIEAg between AIMD guinea pig group and non-AIMD guinea pig group was not significant. Western blotting assay showed only the sera of AIMD guinea pig contained the antibodies against the specific antigens with the molecular of 68 000, 58 000, 42 000 and 28 000.

CONCLUSIONSICIEAg contain many different components, the AIMD might only happen in the guinea pigs in which the special immunization against the main components that could induce this kind of disorder appeared. The inner ear antigens with molecular of 68 000, 58 000, 42 000 and 28 000 might be the main components inducing AIMD in guinea pigs.

Animals ; Autoantigens ; immunology ; Autoimmune Diseases ; immunology ; Disease Models, Animal ; Ear, Inner ; immunology ; Guinea Pigs ; Labyrinth Diseases ; immunology

OBJECTIVETo analyze the clinical and laboratory features of anti-soluble liver antigen/liver-pancreas (SLA/LP) autoantibody positive patients with abnormal liver functions.

METHODSFrom July 1999 to August 2004, 4928 serum samples from patients with abnormal liver functions (ALT >40 U/L) were collected. A series of autoantibody examinations were carried out. Clinical manifestations and laboratory findings of 8 patients with anti-SLA/LP autoantibody positive were reviewed.

RESULTSAmong the 5500 serum samples, 8 cases (6 females and 2 males) with positive anti-SLA/LP autoantibodies were found with complete clinical information. The age of the patients was (27-76) years old. The case histories were from 2 years to 10 years. Of the 8 patients, 6 cases had liver cirrhosis and HBsAg-negative and anti-HCV-negative, active, 1 case had liver cirrhosis with HBsAg-positive, but HBVDNA negative; 1 case had liver cirrhosis and anti-HCV positive, but HCV RNA negative. The 8 cases were all ANA positive with titers of 31:320. Four cases were AMA positive and 2 among these 4 cases were M2 positive. The most frequent symptoms were fatigue, anorexia, nausea, jaundice, abdominal distention and edema of lower limbs. All patients had high hypergammaglobulinemia.

CONCLUSIONAnti-SLA/LP autoantibody was at a low detection rate in the study with females in preponderance, Clinical and laboratory characteristics of the 8 cases were consistent with those of the autoimmune hepatitis (AIH). Testing for anti-SLA autoantibodies helps in the diagnosis of AIH in many patients who may otherwise be misdiagnosed.

Adult ; Aged ; Autoantibodies ; immunology ; Autoantigens ; immunology ; Female ; Hepatitis, Autoimmune ; diagnosis ; immunology ; Humans ; Male ; Middle Aged ; Pancreas ; immunology ; Sequence Homology

T cell recognition of foreign peptide antigen and tolerance to self peptides is key to the proper function of the immune system. Usually, in the thymus T cells that recognize self MHC + self peptides are deleted and those with the potential to recognize self MHC + foreign peptides are selected to mature. However there are exceptions to these rules. Autoimmunity and allergy are two of the most common immune diseases that can be related to recognition of self. Many genes work together to lead to autoimmunity. Of those, particular MHC alleles are the most strongly associated, reflecting the key importance of MHC presentation of self peptides in autoimmunity. T cells specific for combinations of self MHC and self peptides may escape thymus deletion, and thus be able to drive autoimmunity, for several reasons: the relevant self peptide may be presented at low abundance in the thymus but at high level in particular peripheral tissues; the relevant self peptide may bind to MHC in an unusual register, not present in the thymus but apparent elsewhere; finally the relevant self peptide may be post translationally modified in a tissue specific fashion. In some types of allergy, the peptide + MHC combination may also be fully derived from self. However the combination in question may be modified by the presence of other ligands, such as small drug molecules or metal ions. Thus these types of allergies may act like the post translationally modified peptides involved some types of autoimmunity.
Animals ; Autoantigens ; immunology ; Autoimmunity ; HLA Antigens ; immunology ; Humans ; Hypersensitivity ; immunology ; Receptors, Antigen, T-Cell ; metabolism ; T-Lymphocytes ; immunology ; metabolism

To date, efforts to treat autoimmune diseases have primarily focused on the disease symptoms rather than on the cause of the disease. In large part, this is attributed to not knowing the responsible auto-antigens (auto-Ags) for driving the self-reactivity coupled with the poor success of treating autoimmune diseases using oral tolerance methods. Nonetheless, if tolerogenic approaches or methods that stimulate regulatory T (Treg) cells can be devised, these could subdue autoimmune diseases. To forward such efforts, our approach with colonization factor antigen I (CFA/I) fimbriae is to establish bystander immunity to ultimately drive the development of auto-Ag-specific Treg cells. Using an attenuated Salmonella vaccine expressing CFA/I fimbriae, fimbriae-specific Treg cells were induced without compromising the vaccine's capacity to protect against travelers' diarrhea or salmonellosis. By adapting the vaccine's anti-inflammatory properties, it was found that it could also dampen experimental inflammatory diseases resembling multiple sclerosis (MS) and rheumatoid arthritis. Because of this bystander effect, disease-specific Treg cells are eventually induced to resolve disease. Interestingly, this same vaccine could elicit the required Treg cell subset for each disease. For MS-like disease, conventional CD25+ Treg cells are stimulated, but for arthritis CD39+ Treg cells are induced instead. This review article will examine the potential of treating autoimmune diseases without having previous knowledge of the auto-Ag using an innocuous antigen to stimulate Treg cells via the production of transforming growth factor-beta and interleukin-10.
Animals ; Antigens, Bacterial/*immunology ; Arthritis, Rheumatoid/immunology/prevention & control ; Autoantigens/*immunology ; Fimbriae Proteins/*immunology ; Humans ; Multiple Sclerosis/immunology/prevention & control ; Salmonella/*immunology ; T-Lymphocytes, Regulatory/*immunology ; *Vaccination

BACKGROUNDSmD1-amino-acid 83-119 peptide (SmD183-119) is the major epitope of Smith (Sm) antigen, which is specific for adult systemic lupus erythematosus (SLE). The anti-SmD183-119 antibody has exhibited higher sensitivity and specificity than anti-Sm antibody in diagnosing adult SLE. However, the utility of anti-SmD183-119antibodies remains unclear in children with SLE (cSLE). This study aimed to assess the characteristics of anti-SmD183-119antibody in the diagnosis of cSLE.

METHODSSamples from 242 children with different rheumatological and immunological disorders, including autoimmune diseases (SLE [n = 46] and ankylosing spondylitis [AS, n = 11]), nonautoimmune diseases (Henoch-Schonlein purpura [HSP, n = 60], idiopathic thrombocytopenia purpura [n = 27], hematuria [n = 59], and arthralgia [n = 39]) were collected from Shanghai Children's Medical Center from March 6, 2012 to February 27, 2014. Seventy age- and sex-matched patients were enrolled in this study as the negative controls. All the patients' sera were analyzed for the anti-SmD183-119, anti-Sm, anti-U1-nRNP, anti-double-stranded DNA (dsDNA), anti-nucleosome, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB, anti-Scl-70, and anti-histone antibodies using the immunoblotting assay. The differences in sensitivity and specificity between anti-SmD183-119 and anti-Sm antibodies were compared by Chi-square test. The correlations between anti-SmD183-119and other auto-antibodies were analyzed using the Spearman's correlation analysis. A value of P< 0.05 was considered statistically significant.

RESULTSThirty-six out of 46 patients with cSLE were found to be positive for anti-SmD183-119, while 12 patients from the cSLE cohort were found to be positive for anti-Sm. Compared to cSLE, it has been shown that anti-SmD183-119 was only detected in 27.3% of patients with AS and 16.7% of patients with HSP. In comparison with anti-Sm, it has been demonstrated that anti-SmD183-119 had a higher sensitivity (78.3% vs. 26.1%, χ2 = 25.1, P< 0.05) and a lower specificity (90.8% vs. 100%, χ2 = 13.6, P< 0.05) in the diagnosis of cSLE. Further analysis revealed that anti-SmD183-119antibodies were positively correlated with anti-dsDNA, anti-nucleosome, and anti-histone antibodies in cSLE. Moreover, it has been clearly shown that anti-SmD183-119 was more sensitive than anti-Sm in discriminating autoimmune diseases from nonautoimmune disorders in patients with arthralgia or hematuria.

CONCLUSIONSMeasurement of anti-SmD183-119in patients with cSLE has a higher sensitivity and a marginally lower specificity than anti-Sm. It has been suggested that inclusion of anti-SmD183-119testing in the integrated laboratory diagnosis of cSLE may significantly improve the overall sensitivity in child populations.

Autoantibodies ; immunology ; Autoantigens ; immunology ; Child ; Female ; Humans ; Immune System Diseases ; immunology ; Immunoblotting ; Lupus Erythematosus, Systemic ; immunology ; Male ; Peptides ; chemistry ; immunology ; snRNP Core Proteins ; immunology