Autoantigens ; metabolism ; Glycoproteins ; metabolism ; Humans ; Immunity, Innate ; immunology ; Lactoferrin ; metabolism ; Nasopharyngeal Carcinoma ; immunology ; metabolism ; Nasopharyngeal Neoplasms ; immunology ; metabolism ; Phosphoproteins ; metabolism ; Proteins ; metabolism

Autoimmune retinopathy (AIR) is an immune-mediated retinopathy, resulting from an immunologic process caused by the aberrant recognition of retinal antigens as autoantigens. The diagnosis of AIR involves the detection of antiretinal antibodies with concurrent clinical and electrophysiological evidence of retinopathy. A 40-year-old patient presented with progressive loss of bilateral vision over several months. A fundus examination was unremarkable. Spectral domain optical coherence tomography revealed a blurred photoreceptor ellipsoid zone at the subfoveal region in both eyes with more prominent disruption in the left eye. Full-field electroretinography (ERG) showed relatively normal rod and cone responses in the right eye, and decreased photopic bwaves with minimal attenuation of a-waves in the left eye. Multifocal ERG demonstrated slightly reduced amplitude of the inner segment ring in the right eye and decreased amplitudes and delayed latencies of all modalities in the left eye. The patient was suspected to have AIR and it was supported by positive Western blots for 23-kDa protein, enolase (46-kDa), aldolase (40-kDa), 62-kDa and 78-kDa proteins and by immunohistochemical staining of human retinal bipolar and ganglion cells. Despite the immunosuppressive treatment, the destruction of the retinal photoreceptors progressed, and immunosuppressive interventions produced very little visual improvement. We report on what is, to the best of our knowledge, the very first case of serologically confirmed nonparaneoplastic AIR in Korea.
Autoantibodies/*blood/immunology ; Autoantigens ; Autoimmune Diseases/*immunology ; Electroretinography ; Humans ; Immunologic Factors ; Paraneoplastic Syndromes/*immunology ; Paraneoplastic Syndromes, Ocular ; Phosphopyruvate Hydratase ; Recoverin ; Republic of Korea ; Retina/*immunology ; Retinal Diseases/*immunology ; Tomography, Optical Coherence

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

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

INTRODUCTIONAnti-BP180 IgG titres were observed to parallel disease activity in case series of bullous pemphigoid (BP). This study aimed to examine whether anti-BP180 titres are an indicator of disease severity, clinical course and outcome in Asian patients with BP.

MATERIALS AND METHODSThis was a prospective observational study conducted between March 2005 and March 2008 in the Immunodermatology Clinic at the National Skin Centre, Singapore. Disease activity and anti-BP180 IgG titres were measured 4-weekly for 12 weeks and during disease flares and clinical remission. Associations between anti-BP180 titres and disease activity, disease flare, clinical remission and cumulative prednisolone dose were examined.

RESULTSThirty-four patients with newly diagnosed BP were recruited. Median follow-up duration was 3 years. Notable correlations between disease activity and anti-BP180 titres were at baseline (r = 0.51, P = 0.002), and disease flare (r = 0.85, P <0.001). Lower titres at Week 12 were associated with greater likelihood of clinical remission (P = 0.036). Post hoc, patients with anti-BP180 titres above 87.5 U/mL at time of diagnosis who reached remission within 2 years of diagnosis received significantly higher cumulative doses (mg/kg) of prednisolone (median, 72.8; range, 56.5 to 127.1) than those with titres <87.5 U/mL (median, 44.6; range, 32.5 to 80.8); P = 0.025).

CONCLUSIONAnti-BP180 titres may be a useful indicator of disease activity at time of diagnosis and at disease flare. Lower titres at Week 12 may predict greater likelihood of clinical remission. Titres above 87.5 U/mL at time of diagnosis may suggest the need for higher cumulative doses of prednisolone to achieve remission within 2 years.

Adult ; Aged ; Aged, 80 and over ; Antibodies, Anti-Idiotypic ; blood ; Asian Continental Ancestry Group ; Autoantibodies ; blood ; Autoantigens ; blood ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Non-Fibrillar Collagens ; blood ; Outcome Assessment (Health Care) ; Pemphigoid, Bullous ; diagnosis ; ethnology ; immunology ; Predictive Value of Tests ; Prospective Studies ; Singapore

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

OBJECTIVETo highlight current knowledge about M-type phospholipase A2 receptor (PLA2R) which is the first human autoantigen discovered in adult idiopathic membranous nephropathy.

DATA SOURCESRelevant articles published in English from 2000 to present were selected from PubMed. Searches were made using the terms "idiopathic membranous nephropathy, M-type PLA2R and podocyte."

STUDY SELECTIONArticles studying the role of M-type PLA2R in idiopathic membranous nephropathy were reviewed. Articles focusing on the discovery, detection and clinical observation of anti-PLA2R antibodies were selected.

RESULTSM-type PLA2R is a member of the mannose receptor family of proteins, locating on normal human glomeruli as a transmembrane receptor. The anti-PLA2R in serum samples from MN were primarily IgG4 subclass. Technologies applied to detect anti-PLA2R autoantibody are mainly WB, IIFT, ELISA and so on. Studies from domestic and overseas have identified a strongly relationship between circulating anti-PLA2R levels and disease activity.

CONCLUSIONRecent discoveries corresponding to PLA2R facilitate a better understanding on IMN pathogenesis and may provide a new tool to its diagnosis, differential diagnosis, risk evaluation, response monitoring and patient-specific treatment.

Animals ; Autoantigens ; metabolism ; Glomerulonephritis, Membranous ; immunology ; metabolism ; Humans ; Podocytes ; metabolism ; Receptors, Phospholipase A2 ; metabolism

BACKGROUNDMany researches demonstrate that the secondary brain injury which is caused by autoimmune attack toward brain antigens plays an important role in surgical brain injury (SBI). Although traditional immunosuppression can reduce autoimmune attack, it will lower the body immunity. Immune tolerance, by contrast, not only does not lower the body immunity, but also could lighten autoimmunity. This study used thymus tolerance to develop an immune system that is tolerant to autologous cerebrospinal fluid (CSF) and autologous brain tissue so that autoimmune injury can be suppressed following the disruption of the blood-brain barrier, thereby reducing brain damage.

METHODSEighty experimental rabbits were divided into five groups by random number table method: 16 in SBI group (group A), 16 in SBI+CSF drainage group (group B), 16 in SBI+CSF drainage+PBS injection group (group C), 16 in SBI+CSF drainage+CSF intrathymic injection group (group D), and 16 in SBI+brain homogenate intrathymic injection group (group E). Rabbits' CSF was drained in group B; was drained and injected PBS into thymus in group C; was drained and injected CSF into thymus in group D; and was injected brain homogenate in group E. Half of the rabbits in each group were phlebotomized on 1st, 3rd, 7th, and 14th days to observe the changes in IL-l, TGF-β by ELISA test, and CD4CD25 regulatory T cells ratio by flow cytometry, and in other animals brain tissues were taken on 7th day for exploring FasL expression by RT-PCR. The least significant difference (LSD) test was used to make paired comparisons; P < 0.05 was considered statistically significant.

RESULTSThe levels of FasL, TGF-β, and the ratios of CD4CD25 regulatory T cells in groups D and E were apparently higher than those in other three groups (P < 0.05). Likewise, the levels of IL-1 in these two groups were lower than the other three groups (P < 0.05). Moreover, the ratios of CD4CD25 regulatory T cells and the levels of TGF-β in groups B and C were higher than those in group A, but the level of IL-1 was lower than that in group A (P < 0.05). There was no significant difference between groups B and C, and groups D and E.

CONCLUSIONThymic injection of CSF and brain homogenate may be able to reduce inflammation after SBI, so thymus immune tolerance may be a useful therapy to treat SBI.

Animals ; Autoantigens ; administration & dosage ; Brain ; surgery ; Brain Injuries ; etiology ; therapy ; Immune Tolerance ; physiology ; Rabbits ; Thymus Gland ; immunology

OBJECTIVETo evaluate the clinical features of patients with primary biliary cirrhosis (PBC) and positive expression of sp100 autoantibody in order to generate a clinical screening profile that may help to increase early diagnosis and timely initiation of therapy.

METHODSThe clinical data of 70 patients who were diagnosed with PBC by liver biopsy between January 2006 to December 2009 at the Second Affiliated Hospital of Kunming Medical University of Hepatobiliary and Pancreatic Medicine were retrospectively collected for analysis. The patients were divided according to expression of anti-sp100: positive patients, n = 12; negative patients, n = 58. The groups were comparatively analyzed for differences in clinical, biochemical, immunological, and histopathological parameters. Normally distributed data was compared by t-test, and non-normally data was compared by rank-sum test.

RESULTSThere was no significant difference in age among the sp100-positive and sp100-negative patients (51.6 +/- 9.5 vs. 50.0 +/- 14.7 years, P more than 0.05). The sp100-positive group had significantly more women (80.0% vs. 61.9%, X2 = 0.32, P more than 0.05) and more patients with atypical symptoms (18.2% vs. 13.8%) but the difference of the latter did not reach statistical significance. The sp100-positive group had significantly higher levels of alkaline phosphatase (ALP; 466 vs. 163 U/L, Z = 3.71), gamma-glutamyl-transpeptidase (GGT; 728 vs. 154 U/L, Z = 3.38), and immunoglobulin M (IgM; 4.25 +/- 2.86 vs. 2.81 +/- 2.15, t = 2.06, P less than 0.05). Forty of the total patients tested negative for antimitochondrial (AMA)-M2 antibodies, and eight of those were sp100-positive (20.0%) while 18 were antinuclear (ANA) antibody-positive (45.0%). There were significantly more AMA-M2-negative/ANA-positive patients than sp100-positive patients (P = 0.021). Anti-sp100 expression was not associated with the pathological stage of PBC (R1 = 5.500, P more than 0.05).

CONCLUSIONSP100-positive PBC may show a bias towards the female sex, and may be characterized by enhanced serum levels of ALP, GGT, and IgM. Further clinical differences may manifest as the disease progresses, and changes in autoantibodies' expression and liver function markers should be carefully monitored in follow-up.

Adult ; Aged ; Antibodies, Antinuclear ; blood ; Antigens, Nuclear ; immunology ; Autoantibodies ; blood ; Autoantigens ; immunology ; Female ; Humans ; Liver ; pathology ; Liver Cirrhosis, Biliary ; immunology ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

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