Monoclonal antibodies to gliadin were recently found to cross-react with epitopes on rat enterocytes. Two molecules of mol. mass 62 and 66 kDa were isolated from enterocyte lysates by affinity chromatography using antigliadin monoclonal antibodies. The N-terminal amino acid sequence of the 62-kDa protein was determined to be XXXIYFKEQFLD. This amino acid sequence corresponds to amino acid sequence of rat calreticulin. The presence of calreticulin in enterocyte lysates was further confirmed using anticalreticulin serum. Anticalreticulin serum was also used to investigate the reactivity of isolated rat calreticulin. To analyze whether gliadin and calreticulin share similar epitopes recognized by anticalreticulin antibodies, synthetic dodecapeptides derived from the amino acid sequence of alpha gliadin were used in competitive ELISA assay. Two gliadin peptides, QEQVPLVQQQQF and YQLLQELCCQHL, were found to inhibit the binding of rabbit anti-rat calreticulin sera to rat calreticulin. The significant correlation was detected between IgA anticalreticulin and antigliadin antibodies (r = 0.827; P < 0.001) in celiac patients.

• MeSH
• autoantigeny imunologie   MeSH
• celiakie imunologie   MeSH
• gliadin imunologie   MeSH
• imunoglobulin A imunologie   MeSH
• kalretikulin MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mapování epitopu MeSH
• molekulární sekvence - údaje MeSH
• monoklonální protilátky MeSH
• proteiny vázající vápník imunologie   MeSH
• ribonukleoproteiny imunologie   MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• sekvenční seřazení MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• autoantigeny MeSH
• gliadin MeSH
• imunoglobulin A MeSH
• kalretikulin MeSH
• monoklonální protilátky MeSH
• proteiny vázající vápník MeSH
• ribonukleoproteiny MeSH

INTRODUCTION: IgA nephropathy is a chronic renal disease characterized by mesangial immunodeposits that contain autoantigen, which is aberrantly glycosylated IgA1 with some hinge-region O-glycans deficient in galactose. Macroscopic hematuria during an upper respiratory tract infection is common among patients with IgA nephropathy, which suggests a connection between inflammation and disease activity. Interleukin-6 (IL-6) is an inflammatory cytokine involved in IgA immune response. We previously showed that IL-6 selectively increases production of galactose-deficient IgA1 in IgA1-secreting cells from patients with IgA nephropathy. METHODS: We characterized IL-6 signaling pathways involved in the overproduction of galactose-deficient IgA1. To understand molecular mechanisms, IL-6 signaling was analyzed by kinomic activity profiling and Western blotting, followed by confirmation assays using siRNA knock-down and small-molecule inhibitors. RESULTS: STAT3 was differentially activated by IL-6 in IgA1-secreting cells from patients with IgA nephropathy compared with those from healthy control subjects. Specifically, IL-6 induced enhanced and prolonged phosphorylation of STAT3 in the cells from patients with IgA nephropathy, which resulted in overproduction of galactose-deficient IgA1. This IL-6-mediated overproduction of galactose-deficient IgA1 could be blocked by small molecule inhibitors of JAK/STAT signaling. DISCUSSION: Our results revealed that IL-6-induced aberrant activation of STAT3-mediated overproduction of galactose-deficient IgA1. STAT3 signaling pathway may thus represent a new target for disease-specific therapy of IgA nephropathy.

• Klíčová slova
• IgA nephropathy, IgA1, O-glycans, aberrant glycosylation, autoantigen,
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: To describe the prevalence and clinical associations of autoantibodies to a novel autoantigen, eukaryotic initiation factor 3 (eIF3), detected in idiopathic inflammatory myositis. METHODS: Sera or plasma from 678 PM patients were analysed for autoantigen specificity by radio-labelled protein immunoprecipitation (IPP). Samples immunoprecipitating the same novel autoantigens were further analysed by indirect immunofluorescence and IPP using pre-depleted cell extracts. The autoantigen was identified through a combination of IPP and MALDI-TOF mass spectrometry, and confirmed using commercial antibodies and IPP-western blots. Additional samples from patients with DM (668), DM-overlap (80), PM-overlap (191), systemic sclerosis (150), systemic lupus erythematosus (200), Sjogren's syndrome (40), rheumatoid arthritis (50) and healthy controls (150) were serotyped by IPP as disease or healthy controls. RESULTS: IPP revealed a novel pattern in three PM patients (0.44%) that was not found in disease-specific or healthy control sera. Indirect immunofluorescence demonstrated a fine cytoplasmic speckled pattern for all positive patients. Mass spectrometry analysis of the protein complex identified the target autoantigen as eIF3, a cytoplasmic complex with a role in the initiation of translation. Findings were confirmed by IPP-Western blotting. The three anti-eIF3-positive patients had no history of malignancy or interstitial lung disease, and had a favourable response to treatment. CONCLUSION: We report a novel autoantibody in 0.44% of PM patients directed against a cytoplasmic complex of proteins identified as eIF3. Although our findings need further confirmation, anti-eIF3 appears to correlate with a good prognosis and a favourable response to treatment.

• Klíčová slova
• autoantibodies, autoantigens, myositis,
• MeSH
• autoantigeny imunologie   MeSH
• autoprotilátky krev   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• eukaryotický iniciační faktor 3 krev   imunologie   MeSH
• hmotnostní spektrometrie metody   MeSH
• imunoprecipitace metody   MeSH
• imunosupresiva aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymyozitida farmakoterapie   imunologie   patofyziologie   MeSH
• progrese nemoci * MeSH
• referenční hodnoty MeSH
• retrospektivní studie MeSH
• revmatická horečka imunologie   patofyziologie   MeSH
• senzitivita a specificita MeSH
• Sjögrenův syndrom imunologie   patofyziologie   MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• systémový lupus erythematodes imunologie   patofyziologie   MeSH
• western blotting metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• autoantigeny MeSH
• autoprotilátky MeSH
• biologické markery MeSH
• eukaryotický iniciační faktor 3 MeSH
• imunosupresiva MeSH

BACKGROUND: Galactose-deficient O-glycans in the hinge region (HR) of immunoglobulin A1 (IgA1) play a key role in the pathogenesis of IgA nephropathy (IgAN). O-Glycans of circulatory IgA1 consist of N-acetylgalactosamine (GalNAc) with a β1,3-linked galactose; both sugars may be sialylated. In patients with IgAN, α2,6-sialylated GalNAc is a frequent form of the galactose-deficient O-glycans. Prior analyses of IgA1-producing cells had indicated that α2,6-sialyltransferase II (ST6GalNAc-II) is likely responsible for sialylation of GalNAc of galactose-deficient IgA1, but direct evidence is missing. METHODS: We produced a secreted variant of recombinant human ST6GalNAc-II and an IgA1 fragment comprised of Cα1-HR-Cα2. This IgA1 fragment and a synthetic HR peptide with enzymatically attached GalNAc residues served as acceptors. ST6GalNAc-II activity was assessed in vitro and the attachment of sialic acid to these acceptors was detected by lectin blot and mass spectrometry. RESULTS: ST6GalNAc-II was active with both acceptors. High-resolution mass spectrometry analysis revealed that up to three sialic acid residues were added to the GalNAc residues of the HR glycopeptide. CONCLUSIONS: Our data provide direct evidence that ST6GalNAc-II can sialylate GalNAc of galactose-deficient IgA1. As serum levels of galactose-deficient IgA1 with sialylated glycoforms are increased in IgAN patients, our data explain the corresponding part of the biosynthetic pathway.

• Klíčová slova
• IgA nephropathy, aberrant O-glycosylation, galactose-deficient IgA1, immunoglobulin A1, α2,6 sialyltransferase ST6GalNAc-II,
• MeSH
• autoantigeny imunologie   MeSH
• galaktosa nedostatek   MeSH
• glykosylace MeSH
• hmotnostní spektrometrie MeSH
• IgA nefropatie enzymologie   imunologie   patologie   MeSH
• imunoglobulin A metabolismus   MeSH
• kultivované buňky MeSH
• kyselina N-acetylneuraminová metabolismus   MeSH
• lidé MeSH
• rekombinantní proteiny imunologie   metabolismus   MeSH
• sialyltransferasy metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• autoantigeny MeSH
• galactosyl-1-3-N-acetylgalactosaminyl-specific 2,6-sialyltransferase MeSH Prohlížeč
• galaktosa MeSH
• imunoglobulin A MeSH
• kyselina N-acetylneuraminová MeSH
• rekombinantní proteiny MeSH
• sialyltransferasy MeSH

Oxidation of atherogenic low-density lipoproteins (LDL) plays a key role in the pathogenesis of atherosclerosis. Oxidation stress and inflammation are closely interrelated and they can potentiate one another. In the subendothelial space of the arterial intima, monocytes/macrophages become activated and phagocyte oxidized LDL (oxLDL) via scavenger receptors. It has been demonstrated that oxLDL forms complex with plasma β2-glycoprotein I (β2GPI) and becomes autoantigenic triggering synthesis of specific antiphosholipid antibodies. It has been documented that oxLDL/β2GPI in immune complex with IgG autoantibody is internalized by macrophages through the Fcγ receptor. Increased levels of oxLDL/β2GPI were first observed in patients with systemic lupus erythematodes (SLE) and antiphospholipid syndrome (APS), further in individuals with coronary heart disease (CHD) and type 2 diabetes mellitus (DM2T). In a prospective study, initial plasma concentrations of oxLDL/β2GPI correlated with the number and severity of cardiovascular events in patients with chronic CHD over a 2-year period.Key words: atherosclerosis - β2-glycoprotein I - inflammation - oxidative stress - oxLDL.

• MeSH
• ateroskleróza krev   imunologie   MeSH
• autoimunitní nemoci imunologie   MeSH
• beta-2-glykoprotein I krev   MeSH
• koronární nemoc krev   imunologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoproteiny LDL krev   MeSH
• prospektivní studie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-2-glykoprotein I MeSH
• lipoproteiny LDL MeSH
• oxidized low density lipoprotein MeSH Prohlížeč

Celiac disease is an autoimmune disorder in which gluten peptides presented by specific HLA-DQ2- and HLA-DQ8-positive antigen presenting cells elicit immune response in connective tissue of lamina propria. Immunoglobulin A (IgA) antiendomysial antibodies are specific for celiac disease and are used for screening, diagnosis and follow-up of this disease with an almost 100% sensitivity and specificity. The major target antigen of IgA antiendomysial antibodies was identified as tissue transglutaminase; nevertheless, the existence of the additional unique celiac disease-specific autoantigens is anticipated. In this study we have utilized a proteomic approach in order to search out new autoantigens recognized by serum antibodies of patients with active celiac disease. We report the detection of 11 proteins that were immunorecognized with various frequencies by sera of patients with celiac disease. Four autoantigens were identified by mass fingerprinting approach as actin, ATP synthase beta chain and two charge variants of enolase alpha. While production of IgA antibodies against actin molecules were described earlier, the existence of autoantibodies to ATP synthase beta chain and enolase alpha species in sera collected from patients with active celiac disease are described for the first time. These results are suggestive of the existence of additional celiac disease autoantigens with possible diagnostic utility.

• MeSH
• 2D gelová elektroforéza MeSH
• autoantigeny analýza   krev   imunologie   MeSH
• autoprotilátky krev   imunologie   MeSH
• celiakie krev   diagnóza   imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• fosfopyruváthydratasa krev   imunologie   MeSH
• HLA-DQ antigeny krev   MeSH
• hmotnostní spektrometrie MeSH
• imunoglobulin A krev   imunologie   MeSH
• lidé MeSH
• proteom analýza   MeSH
• proteomika * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• autoantigeny MeSH
• autoprotilátky MeSH
• fosfopyruváthydratasa MeSH
• HLA-DQ antigeny MeSH
• imunoglobulin A MeSH
• proteom MeSH

UNLABELLED: Perfect maternal diabetes compensation is crucial for the outcome of the baby. However, little is known how hyperglycaemia influences the specific immune response. Furthermore, babies of type 1 diabetes (T1D) mothers have less risk of development T1D than babies with a T1D father. This study aimed to analyze the effect of maternal hyperglycaemia on newborns with focus on the response to diabetes-associated autoantigens. POPULATIONS: (1) Newborns of T1D mothers split into groups according to maternal diabetes compensation during the 3rd trimester: perfect (n = 15) or acceptable (n = 25) compensation. (2) newborns with T1D father (n = 12) (3) newborns with a mother treated for either gestational or type 2 diabetes (n = 10) (4) control newborns (n = 25). Spontaneous as well as diabetes-associated autoantigen-stimulated production of 23 cytokines and chemokines were tested using protein microarray. In addition, the influence of glucose on cytokine and chemokine responsiveness was analyzed in vitro. The study groups differed in their spontaneous as well as stimulated cytokine and chemokine spectra. A prominent Th1 response (high IFN-gamma) from autoantigen stimulation was observed especially in babies of T1D fathers (P = 0.001) and also in mothers with perfect diabetes compensation during the 3rd trimester (P = 0.016) in comparison with control newborns. By contrast, cord blood mononuclear cells cultivated in vitro in high glucose concentration decreased the diabetogenic stimulated Th1 cytokine response. Maternal 'sweet' as well as 'autoimmune environment' may both lead to lower occurrence of T1D within their offspring. Further studies will reveal the exact immunological mechanism of this observation.

• MeSH
• autoantigeny imunologie   MeSH
• čipová analýza proteinů MeSH
• cytokiny biosyntéza   účinky léků   imunologie   MeSH
• diabetes mellitus 1. typu imunologie   MeSH
• dospělí MeSH
• fetální krev imunologie   metabolismus   MeSH
• glukosa farmakologie   MeSH
• glutamát dekarboxyláza farmakologie   MeSH
• hyperglykemie imunologie   MeSH
• leukocyty mononukleární účinky léků   imunologie   MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství při diabetu imunologie   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoantigeny MeSH
• cytokiny MeSH
• GAD55, human MeSH Prohlížeč
• glukosa MeSH
• glutamát dekarboxyláza MeSH

Type 1 Diabetes (T1D) is considered to be a T-helper- (Th-) 1 autoimmune disease; however, T1D pathogenesis likely involves many factors, and sufficient tools for autoreactive T cell detection for the study of this disease are currently lacking. In this study, using gene expression microarrays, we analysed the effect of diabetes-associated autoantigens on peripheral blood mononuclear cells (PBMCs) with the purpose of identifying (pre)diabetes-associated cell processes. Twelve patients with recent onset T1D, 18 first-degree relatives of the TD1 patients (DRL; 9/18 autoantibody positive), and 13 healthy controls (DV) were tested. PBMCs from these individuals were stimulated with a cocktail of diabetes-associated autoantigens (proinsulin, IA-2, and GAD65-derived peptides). After 72 hours, gene expression was evaluated by high-density gene microarray. The greatest number of functional differences was observed between relatives and controls (69 pathways), from which 15% of the pathways belonged to "immune response-related" processes. In the T1D versus controls comparison, more pathways (24%) were classified as "immune response-related." Important pathways that were identified using data from the T1D versus controls comparison were pathways involving antigen presentation by MHCII, the activation of Th17 and Th22 responses, and cytoskeleton rearrangement-related processes. Genes involved in Th17 and TGF-beta cascades may represent novel, promising (pre)diabetes biomarkers.

• MeSH
• autoantigeny imunologie   metabolismus   MeSH
• autoprotilátky imunologie   metabolismus   MeSH
• diabetes mellitus 1. typu genetika   imunologie   metabolismus   MeSH
• dítě MeSH
• dospělí MeSH
• exprese genu MeSH
• leukocyty mononukleární imunologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• prediabetes genetika   imunologie   metabolismus   MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• autoantigeny MeSH
• autoprotilátky MeSH

Autoantibodies directed against various self-antigens comprise a heterogeneous group of immunoglobulins, which differ in their qualitative and quantitative features. An important qualitative characteristic of antibodies is affinity/avidity, which changes in the process of its maturation during the immune response.This study is aimed to summarize the knowledge about avidity of selected autoantibodies in certain autoimmune diseases. The avidity of various autoantibodies differs under distinct clinical situations. High-, moderate or low-avidity may be found in biological fluids in patients with autoimmune diseases.The avidity maturation associated with progression from low to high values typical for antibodies against exogenous antigens is not always uniform in autoimmune diseases; therefore, the avidity of each autoantibody should be judged individually. Some studies promise the possible benefit of avidity examination for the refinement of diagnosis and prediction of selected autoimmune diseases.Key words: affinity - anti-citrullinated protein antibodies - anti-glomerular basement membrane antibodies - anti-glutamate decarboxylase antibodies - anti-insulin antibodies - autoantibodies - avidity - onconeuronal antibodies.

• MeSH
• afinita protilátek MeSH
• autoantigeny * MeSH
• autoimunitní nemoci diagnóza   imunologie   MeSH
• autoprotilátky * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiglomerular basement membrane antibody MeSH Prohlížeč
• autoantigeny * MeSH
• autoprotilátky * MeSH

Type 1 diabetes mellitus (T1 DM) is caused by autoimmune-mediated and idiopathic beta-cell destruction of the pancreatic islets of Langerhans resulting in absolute insulin deficiency. Susceptibility to T1 DM is influenced by both genetic and environmental factors. It is generally believed that in genetically susceptible individuals, the disease is triggered by environmental agents, such as viral infections, dietary factors in early infancy, or climatic influences. Many candidate genes for diabetes have been reported; those within the Major Histocompatibility Complex being among the most important. The most common autoantigens are insulin, glutamic acid decarboxylase 65, insuloma-associated antigen 2, and zinc transporter ZnT8. The destruction of beta-cells is mediated mainly by cellular mechanisms; antibodies only seem to reflect the ongoing autoimmune processes and are not directly involved in the tissue damage. They, however, appear prior to the onset of insulin deficiency which makes them suitable for use in the prevention of the disease.

• Klíčová slova
• T, and NKT cells., autoantigens - autoantibodies - HLA alleles - insuline - B,
• MeSH
• autoantigeny genetika   imunologie   MeSH
• diabetes mellitus 1. typu genetika   imunologie   MeSH
• Langerhansovy ostrůvky imunologie   MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• autoantigeny MeSH