OBJECTIVE: Diagnosing autoimmune encephalitis (AIE) is difficult in patients with less fulminant diseases such as epilepsy. However, recognition is important, as patients require immunotherapy. This study aims to identify antibodies in patients with focal epilepsy of unknown etiology, and to create a score to preselect patients requiring testing. METHODS: In this prospective, multicenter cohort study, adults with focal epilepsy of unknown etiology, without recognized AIE, were included, between December 2014 and December 2017, and followed for 1 year. Serum, and if available cerebrospinal fluid, were analyzed using different laboratory techniques. The ACES score was created using factors favoring an autoimmune etiology of seizures (AES), as determined by multivariate logistic regression. The model was externally validated and evaluated using the Concordance (C) statistic. RESULTS: We included 582 patients, with median epilepsy duration of 8 years (interquartile range = 2-18). Twenty patients (3.4%) had AES, of whom 3 had anti-leucine-rich glioma inactivated 1, 3 had anti-contactin-associated protein-like 2, 1 had anti-N-methyl-D-aspartate receptor, and 13 had anti-glutamic acid decarboxylase 65 (enzyme-linked immunosorbent assay concentrations >10,000IU/ml). Risk factors for AES were temporal magnetic resonance imaging hyperintensities (odds ratio [OR] = 255.3, 95% confidence interval [CI] = 19.6-3332.2, p < 0.0001), autoimmune diseases (OR = 13.31, 95% CI = 3.1-56.6, p = 0.0005), behavioral changes (OR 12.3, 95% CI = 3.2-49.9, p = 0.0003), autonomic symptoms (OR = 13.3, 95% CI = 3.1-56.6, p = 0.0005), cognitive symptoms (OR = 30.6, 95% CI = 2.4-382.7, p = 0.009), and speech problems (OR = 9.6, 95% CI = 2.0-46.7, p = 0.005). The internally validated C statistic was 0.95, and 0.92 in the validation cohort (n = 128). Assigning each factor 1 point, an antibodies contributing to focal epilepsy signs and symptoms (ACES) score ≥ 2 had a sensitivity of 100% to detect AES, and a specificity of 84.9%. INTERPRETATION: Specific signs point toward AES in focal epilepsy of unknown etiology. The ACES score (cutoff ≥ 2) is useful to select patients requiring antibody testing. ANN NEUROL 2021;89:698-710.

• MeSH
• autoimunitní nemoci diagnostické zobrazování   imunologie   psychologie   MeSH
• autoprotilátky analýza   MeSH
• chování MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• epilepsie parciální diagnostické zobrazování   imunologie   psychologie   MeSH
• glutamát dekarboxyláza genetika   imunologie   MeSH
• kognitivní poruchy etiologie   psychologie   MeSH
• kohortové studie MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• záchvaty diagnostické zobrazování   etiologie   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Nizozemsko MeSH
• Názvy látek
• autoprotilátky MeSH
• glutamát dekarboxyláza MeSH
• glutamate decarboxylase 2 MeSH Prohlížeč

PURPOSE: Epileptic seizures are a common manifestation of autoimmune encephalitis, but the role of neural antibodies in long-term epilepsy remains unclear. The aim of this study was to assess the prevalence of neural-surface antibodies (NSAbs) and antibodies against glutamic acid decarboxylase (GAD) in patients with chronic temporal lobe epilepsy (TLE). METHOD: Patients with an electro-clinical diagnosis of TLE and a disease duration longer than one year were included. NSAbs (LGI1, CASPR2, AMPAR1/2, NMDAR, GABABR) and antibodies against GAD were detected. Only patients with significant antibody levels in serum, and/or positivity in CSF (according to antibody subtype), were enrolled in the seropositive group. Cohorts of seropositive and seronegative patients were compared regarding clinical and imaging data. RESULTS: Significant serum levels of antibodies were detected in eight out of 163 (5%) TLE patients (CASPR2 n = 2, GAD n = 3, LGI1 n = 2, and GABABR n = 1). In four of them, antibodies were detected in the CSF as well (CASPR2 in one, GAD in three). Five seropositive patients had uni- or bilateral temporal lobe lesions on MRI and three patients were non-lesional. All seropositive patients had TLE of unknown cause. Seropositive patients had higher age at epilepsy onset and autoimmune comorbidity, but did not differ in other clinical, EEG or neuroimaging characteristics. Response to immunotherapy (seizure reduction >50%) was observed in three of the six patients treated. CONCLUSIONS: Besides older age at epilepsy onset and autoimmune comorbidity, seropositive patients cannot be distinguished from seronegative patients on the basis of clinical, EEG or neuroimaging data.

• Klíčová slova
• Anti-GAD, Autoimmune epilepsy, Neural antibodies, Neural-Surface antibodies, Temporal lobe epilepsy,
• MeSH
• autoimunitní nemoci komplikace   epidemiologie   MeSH
• autoprotilátky krev   MeSH
• chronická nemoc MeSH
• dospělí MeSH
• epilepsie temporálního laloku komplikace   epidemiologie   patofyziologie   terapie   MeSH
• glutamát dekarboxyláza imunologie   MeSH
• imunoterapie MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• prevalence MeSH
• prospektivní studie MeSH
• proteiny nervové tkáně imunologie   MeSH
• senioři MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• autoprotilátky MeSH
• glutamát dekarboxyláza MeSH
• proteiny nervové tkáně MeSH

UNLABELLED: Tolerogenic DCs (tolDCs) are being researched as a promising intervention strategy also in autoimmune diseases including type 1 diabetes (T1D). T1D is a T-cell-mediated, organ-specific disease with several well-defined and rather specific autoantigens, i.e., proinsulin, insulin, glutamic acid decarboxylase 65 (GAD65), that have been used in animal as well as human intervention trials in attempts to achieve a more efficient, specific immunotherapy. In this study, we have tested tolerogenic DCs for their effectiveness to prevent adoptive transfer of diabetes by diabetogenic splenocytes into non-obese diabetes (NOD)-severe combined immunodeficiency (NOD-SCID) recipients. While i.p. application of tolDCs prepared from bone marrow of prediabetic NOD mice by vitamin D2 and dexamethasone significantly reduced diabetes transfer into the NOD-SCID females, this effect was completely abolished when tolDCs were loaded with the mouse recombinant GAD65, but also with a control protein-ovalbumin (OVA). The effect was not dependent on the presence of serum in the tolDC culture. Similar results were observed in NOD mice. Removal of possible bystander antigen-presenting cells within the diabetogenic splenocytes by negative magnetic sorting of T cells did not alter this surprising effect. Tolerogenic DCs loaded with an immunodominant mouse GAD65 peptide also displayed diminished diabetes-preventive effect. Tolerogenic DCs were characterized by surface maturation markers (CD40, CD80, CD86, MHC II) and the lipopolysaccharide stability test. Data from alloreactive T cell proliferation and cytokine induction assays (IFN-γ) did not reveal the differences observed in the diabetes incidence. Migration of tolDCs, tolDCs-GAD65 and tolDCs-OVA to spleen, mesenteric- and pancreatic lymph nodes displayed similar, mucosal pattern with highest accumulation in pancreatic lymph nodes present up to 9 days after the i.p. APPLICATION: These data document that mechanisms by which tolDCs operate in vivo require much better understanding for improving efficacy of this promising cell therapy, especially in the presence of an antigen, e.g., GAD65.

• Klíčová slova
• autoantigen, cell therapy, dendritic cells, glutamic acid decarboxylase 65, non-obese diabetes mice, non-obese diabetes-severe combined immunodeficiency mouse, tolerogenic, type 1 diabetes,
• MeSH
• autoantigeny imunologie   MeSH
• dendritické buňky imunologie   MeSH
• diabetes mellitus 1. typu imunologie   MeSH
• glutamát dekarboxyláza imunologie   MeSH
• imunologická tolerance imunologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši inbrední NOD MeSH
• myši SCID MeSH
• myši MeSH
• převzatá imunita MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoantigeny MeSH
• glutamát dekarboxyláza MeSH
• glutamate decarboxylase 2 MeSH Prohlížeč

The aim of this study was to describe the frequency and distribution of Saffold virus in longitudinal stool samples from children, and test for association with development of persistent autoantibodies predictive of type 1 diabetes. A cohort of Norwegian children carrying the HLA genotype associated with highest risk of type 1 diabetes ("DR4-DQ8/DR3-DQ2") was followed with monthly stool samples from 3 to 35 months of age. Blood samples were tested for autoantibodies to insulin, glutamic acid decarboxylase65 and Islet Antigen-2. 2077 stool samples from 27 children with ≥ 2 repeatedly positive islet autoantibodies (cases), and 53 matched controls were analysed for Saffold virus genomic RNA by semi-quantitative real-time reverse transcriptase PCR. Saffold virus was found in 53 of 2077 (2.6%) samples, with similar proportions between cases (2.5%) and controls (2.6%). The probability of being infected by 3 years of age was 28% (95% CI 0.18-0.40). Viral quantities ranged from <1 to almost 105 copies/μl. Estimated odds ratio between islet autoimmunity and infection episodes prior to seroconversion was 1.98 (95% CI: 0.57-6.91, p = 0.29). Saffold virus had no statistically significant association with islet autoimmunity.

• MeSH
• autoprotilátky krev   MeSH
• Cardiovirus izolace a purifikace   MeSH
• diabetes mellitus 1. typu krev   genetika   imunologie   MeSH
• feces virologie   MeSH
• glutamát dekarboxyláza imunologie   MeSH
• HLA-DQ antigeny genetika   MeSH
• infekce viry z rodu Cardiovirus krev   imunologie   virologie   MeSH
• inzulin imunologie   MeSH
• kojenec MeSH
• lidé MeSH
• longitudinální studie MeSH
• předškolní dítě MeSH
• tyrosinfosfatasy receptorového typu, třída 8 imunologie   MeSH
• virová nálož MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• glutamát dekarboxyláza MeSH
• HLA-DQ antigeny MeSH
• inzulin MeSH
• PTPRN protein, human MeSH Prohlížeč
• tyrosinfosfatasy receptorového typu, třída 8 MeSH

Type 1 diabetes (T1D) is an autoimmune disorder characterised by the immune-mediated destruction of insulin-producing pancreatic beta cells. The inflammatory process appears to be primarily mediated by pro-inflammatory Th1 lymphocytes, while the role Th17 cells in T1D is currently being investigated. T1D is characterised by the presence of autoantigen-specific autoantibodies. This study was conducted using patients with confirmed T1D and healthy control subjects. We examined the effect of the patient's autoantibody profile on peripheral blood mononuclear cell (PBMC) cytokine production following stimulation with the major diabetogenic autoantigens GAD65 and IA2. IFN-gamma and IL17 production was detected by ELISPOT and the ratio of basic cellular populations in PBMCs was measured by flow cytometry. We demonstrated a significant interaction between the patient's autoantibody profile and mode of stimulation. This suggests that autoantigen stimulation has a different effect on different groups of patients depending on their autoantibody profile. An increased production of IL17 was found in patients with high IA2 autoantibodies compared to patients with low levels of autoantibodies and healthy controls regardless of the mode of stimulation. The titre of IA2 autoantibodies positively correlates with the proportion of Tc lymphocytes and negatively correlates with the proportion of Th lymphocytes. Our results show that a patient's autoantibody profile reflects the type of cellular immune responses. It seems that the high titre of IA2 autoantibodies is related to increased production of IL17 and an increased proportion of Tc lymphocytes. This finding may be useful in designing immunointervention studies to prevent T1D.

• Klíčová slova
• Autoantibodies, GAD65, IA2, IL17, Type 1 diabetes,
• MeSH
• autoprotilátky krev   imunologie   MeSH
• diabetes mellitus 1. typu krev   imunologie   MeSH
• dítě MeSH
• glutamát dekarboxyláza imunologie   MeSH
• interferon gama biosyntéza   krev   MeSH
• interleukin-17 biosyntéza   krev   MeSH
• leukocyty mononukleární metabolismus   MeSH
• lidé MeSH
• předškolní dítě MeSH
• průtoková cytometrie MeSH
• regulační T-lymfocyty imunologie   MeSH
• T-lymfocyty pomocné-indukující imunologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• glutamát dekarboxyláza MeSH
• glutamate decarboxylase 2 MeSH Prohlížeč
• interferon gama MeSH
• interleukin-17 MeSH

AIMS: Islet cell autoantibodies are associated with autoimmune insulitis and belong to the diagnostic criteria of type 1 diabetes mellitus. However, growing evidence suggests that autoantibodies are present in other types of diabetes. Here, we focus on the autoantibody incidence in Czech patients with maturity-onset diabetes of the young and analyse their functional relevance in terms of diabetes onset and control. METHODS: Autoantibodies against glutamic acid decarboxylase (GAD) 65 and protein tyrosine phosphatase islet antigen 2 (IA-2) were measured in a cohort of 28 Czech patients with maturity-onset diabetes of the young, all confirmed by genetic testing. Selected clinical data were correlated to the status and kinetics of autoantibodies. RESULTS: One quarter of patients with maturity-onset diabetes of the young examined (7/28; 25%) was positive for GAD or IA-2 autoantibodies. GAD autoantibodies were more prevalent (7/7) than IA-2 autoantibodies (1/7). The incidence of autoantibodies did not correlate with human leukocyte antigen status. The patients who were positive for the autoantibodies developed diabetes later than those who were autoantibody-negative, but had worse glycaemic control (increased HbA1c ). Expression of autoantibodies decreased with any improvement of diabetes compensation. Only one patient did not correspond to the above and displayed signs of combined signs of maturity-onset diabetes of the young and Type 1 diabetes. CONCLUSIONS: The data suggest transient but highly prevalent islet cell autoantibody expression in Czech patients with maturity-onset diabetes of the young. The autoantibodies were found in patients with delayed diabetes onset, and in times of insufficient diabetes control. As improvement of glycaemic control was associated with a decrease in levels of autoantibodies, their presence may reflect the kinetics of β-cell destruction induced by causes other than autoimmune ones.

• MeSH
• autoprotilátky imunologie   MeSH
• diabetes mellitus 2. typu epidemiologie   imunologie   metabolismus   MeSH
• dítě MeSH
• dospělí MeSH
• glukokinasa genetika   MeSH
• glutamát dekarboxyláza imunologie   MeSH
• glykovaný hemoglobin metabolismus   MeSH
• hepatocytární jaderný faktor 1-alfa genetika   MeSH
• hepatocytární jaderný faktor 4 genetika   MeSH
• kohortové studie MeSH
• Langerhansovy ostrůvky imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• tyrosinfosfatasy receptorového typu, třída 8 imunologie   MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• glukokinasa MeSH
• glutamát dekarboxyláza MeSH
• glykovaný hemoglobin MeSH
• hemoglobin A1c protein, human MeSH Prohlížeč
• hepatocytární jaderný faktor 1-alfa MeSH
• hepatocytární jaderný faktor 4 MeSH
• HNF1A protein, human MeSH Prohlížeč
• HNF4A protein, human MeSH Prohlížeč
• tyrosinfosfatasy receptorového typu, třída 8 MeSH

The determination of GADA may be useful for clinical classification of diabetes mellitus (DM) in clinically unclear cases. This GADA positivity may persist in any diabetics Type 1 Diabetes Mellitus (T1D) with an onset in adulthood and Late Autoimmune Diabetes of Adults (LADA) many years after appearance of DM. The study was aimed at comparing the levels of GADA between both diabetic subsets with their clinical parameters, age of onset DM, period of insulin need, body mass index, HbA1C, fasting and postprandial C-peptide, risky HLA-DRB1* alleles, occurrence of micro- and macrovascular diabetic complications. Further analysis of GADA titers in different time consequences to the development of DM and relations to IA-2 were made. In the study, we included 130 diabetics with an onset of diabetes (T1D or LADA) 35+ y. who were hospitalized and afterwards long-term observed in the diabetological outpatient department. Out of this number there were 62 men and 68 women of the average age 65.5 +/- 14.0 y. (range 35-93 y.). 54 were assessed as the T1D patients and 76 as the LADA ones. Patients of the T1D subgroup were GADA positive 22 times and of the LADA subgroup 21 times. LADA 2 patients that were GADA negative were more obese than GADA positive LADA diabetics (p < 0.01). Also postprandial C-peptide was higher in LADA patients GADA negative (p < 0.05). Other clinical characteristics were without statistically significant differences. We found in our diabetic patients a relation between alleles HLA-DRB1*03 and particularly combination with HLA-DRB1*04 with positive GADA levels. In the GADA negative group obesity, coronary heart disease, hypertension, syndrome of diabetic foot and dyslipidaemia appeared more frequently (OR = 2.8; 3.1; 6.2 and 2.4). We found no significant differences in observed parameters--comparison GADA positivity and negativity according to the duration of DM. GADA positive were even 10 y. duration 16 times and after 20 y. even 6 times. Recent DM had positive GADA in 11 cases and 13 cases of recent DM had GADA negative. IA-2 antibodies were positive (> 1.0 U/ml) 18 times altogether and always with positive GADA, but only 7 times in recent DM. The presence of elevated GADA identifies patients unequivocally suitable for early insulin therapy. Our observations and experiences confirm that GADA can be found increased after more than 10-20 years duration of DM, although in decreasing trend.

• MeSH
• alely MeSH
• autoprotilátky krev   MeSH
• C-peptid krev   MeSH
• diabetes mellitus 1. typu krev   genetika   imunologie   MeSH
• dospělí MeSH
• glutamát dekarboxyláza imunologie   MeSH
• HLA-DR antigeny genetika   MeSH
• HLA-DRB1 řetězec MeSH
• index tělesné hmotnosti MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tyrosinfosfatasy receptorového typu, třída 8 imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• autoprotilátky MeSH
• C-peptid MeSH
• glutamát dekarboxyláza MeSH
• glutamate decarboxylase 1 MeSH Prohlížeč
• HLA-DR antigeny MeSH
• HLA-DRB1 řetězec MeSH
• HLA-DRB1*04 antigen MeSH Prohlížeč
• ICA512 autoantibody MeSH Prohlížeč
• tyrosinfosfatasy receptorového typu, třída 8 MeSH

OBJECTIVE: A role of autoreactive T cells for type 1 diabetes pathogenesis is considered crucial. In our pilot study we addressed if autoreactive mononuclear cells are present also in peripheral blood of patients with other specific forms of diabetes as cystic fibrosis related diabetes (CFRD). METHODS: Cellular immune responses to a known beta-cell autoantigen (GAD65 and GAD65 derived peptides) were analysed by ELISPOT (IFN-gamma) and by protein microarray analysis in four patients suffering from CFRD, in four cystic fibrosis (CF) patients without diabetes, in eight type 1 diabetes patients (without CF) and in four healthy controls. RESULTS: Response to the autoantigen GAD65 (protein and peptides) was observed in 7/8 patients suffering from CF and in all type 1 diabetes patients. Post-stimulation production of Th1 cytokines (IFN-gamma, TNF-beta) was observed in 2/4 CFRD, 1/4 CF patients and in 7/8 type 1 diabetes patients. All these patients carry prodiabetogenic HLA-DQ genotype. Th2- and Th3 type of cytokine pattern was observed in 2/4 CF patients. Production of IL-8 was observed in the third CFRD as well as in the third CF patient and in 1/8 type 1 diabetes patient and borderline production of this chemokine was also observed in 2/4 healthy controls. No reaction was observed in the other 2/4 healthy controls and in the fourth CFRD patient who carried a strongly protective genotype and did not produce autoantibodies. The most potent peptide of GAD65 was amino acids 509-528. CONCLUSIONS: We consider our observations as a sign of a reaction directed against the self-antigen GAD65 that are closely connected to type 1 diabetes. In CF patients who do not develop diabetes autoreactive mechanisms are very probably efficiently suppressed by immune self-tolerance mechanisms. CFRD patients are a heterogenic group. To disclose those who may display features of autoimmune diabetes could have an impact for their therapy and prognosis.

• MeSH
• autoprotilátky krev   imunologie   MeSH
• čipová analýza proteinů MeSH
• cystická fibróza komplikace   imunologie   MeSH
• diabetes mellitus etiologie   imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• glutamát dekarboxyláza imunologie   MeSH
• HLA-DQ antigeny imunologie   MeSH
• interferon gama krev   MeSH
• interleukin-8 krev   MeSH
• izoenzymy imunologie   MeSH
• leukocyty mononukleární imunologie   MeSH
• lidé MeSH
• lymfotoxin-alfa krev   MeSH
• mladiství MeSH
• pilotní projekty MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• glutamát dekarboxyláza MeSH
• glutamate decarboxylase 2 MeSH Prohlížeč
• HLA-DQ antigeny MeSH
• interferon gama MeSH
• interleukin-8 MeSH
• izoenzymy MeSH
• lymfotoxin-alfa MeSH

As an autoimmune disease, type 1 diabetes mellitus (DM) can be associated with other autoimmune disorders. The aim of this study was to detect subclinically associated autoimmune thyroid disease, coeliac disease, and Addison's disease. The presence of autoantibodies was evaluated with special regard to the control of diabetes and to the clinical status of the patient. Fifty-one type 1 diabetic patients (22 men, 29 women, mean age 37+/-11 years, mean duration of diabetes 16+/-13 years) were included into this study. Specific antibodies to islet antigens--glutamic acid decarboxylase (GAD65), protein thyrosine phosphatase IA-2alpha, and to thyroid autoantigens--thyroid microsomal peroxidase (TPO) and thyroglobulin (TG) and also thyroid stimulating hormone (TSH) were measured by RIA. Autoantigens of the small intestine--tissue transglutaminase autoantibodies (ATTG), IgA and IgG antibodies to gliadin (AGA-IgA, AGA-IgG) were evaluated by ELISA. Endomysial autoantibodies (EMA) and adrenal cortex antibodies (ACA) were detected by indirect immunofluorescence microscopy. Eleven new cases of thyreopathy (22 % of patients) were detected by the assessment of thyroid autoantibodies and TSH. Two new cases of thyreotoxicosis were diagnosed during the study. Coeliac disease was diagnosed in at least two cases. Addison's disease was not diagnosed, although the ACA were positive in two patients. No influence of single or combined autoantibody positivity on the control of diabetes was found if normal organ function was preserved. In both patients with thyreotoxicosis the control of diabetes was worsened and improved after treatment. The screening of autoantibodies in type 1 diabetic patients could reveal subclinical cases of AITD or coeliac disease. Subclinical forms of these disorders have no influence on diabetes control. However, impaired organ function may be associated with the worsened control of diabetes as we demonstrated on two newly diagnosed cases of thyreotoxicosis. We suggest the need for the follow-up of patients with positive autoantibodies because further deterioration of the respective organs can be expected.

• MeSH
• Addisonova nemoc komplikace   imunologie   MeSH
• autoimunita * MeSH
• autoimunitní tyreoiditida komplikace   imunologie   MeSH
• autoprotilátky krev   MeSH
• celiakie komplikace   imunologie   MeSH
• diabetes mellitus 1. typu komplikace   imunologie   MeSH
• dospělí MeSH
• gliadin imunologie   MeSH
• glutamát dekarboxyláza imunologie   MeSH
• imunoglobuliny stimulující tyreoideu krev   MeSH
• izoenzymy imunologie   MeSH
• kůra nadledvin imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• plošný screening MeSH
• transglutaminasy imunologie   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
• Názvy látek
• anti-thyroglobulin MeSH Prohlížeč
• autoprotilátky MeSH
• gliadin MeSH
• glutamát dekarboxyláza MeSH
• glutamate decarboxylase 2 MeSH Prohlížeč
• imunoglobuliny stimulující tyreoideu MeSH
• izoenzymy MeSH
• thyroid microsomal antibodies MeSH Prohlížeč
• transglutaminasy MeSH

OBJECTIVE: Verification of the possibility to predict diabetes in the neonates of mothers and fathers with Type 1 diabetes. DESIGN: Prospective clinical study. SETTING: Mother and Child Care Institute, Prague. Paediatric Clinic of the 2nd Faculty of Medicine at the Charles University, Prague. METHODS: In 31 neonates of mothers and fathers with Type 1 diabetes, the long-term and short-term risk of the occurrence of Type 1 diabetes was established. The genotypification of HLA, DQB1, HLA DQA1 and DRB1 *04 was carried out by using the PCR method to establish the long-term risk and according to the result of the examination, the examined child was included into one of the five categories of genetic risk. In all the monitored persons, the levels of antibodies against GAD65, IA-2 and IRA insulin were repeatedly identified by means of the methods, which are the markers of autoimmune insulitis and show the short-term risk of the occurrence of diabetes. The function-related examination of secretion of beta cells was carried out by using the intravenous glucose tolerance test (i.v. GTT) in children with significant titres of one or more antibodies. RESULTS: A very high risk of the occurrence of Type 1 diabetes was identified in 1 child with the genotype DQA1*03-DQB1*0201/DQA1*05-DQB1*0302 (3.23%); an increased risk was identified in 12 children (38.71%); a medium risk was identified in 11 children (35.48%); a relatively low risk was identified in 3 child (9,68%) and a low risk was identified in 4 children (12,90%). In 4 children (12.9%), a strongly protective alelle DQB1*0602 was found. In 4 children, positivity for one of the antibodies was identified. In 1 child of a diabetic father with an increased genetic risk, there was a decrease in the titre of antibodies in the case of repeated check and function-related examination of the insulin secretion (FPIR) will be carried out. In another child, disappearance of antibodies was identified when samples were taken for verification; function-related examination of insulin secretion produced normal results, and the child has remained without clinical manifestation of diabetes. In a third child, the positivity of the antibodies from the umbilical blood was only temporary and was probably caused by a passive transfer from the mother; now, when repeated checks were made, the antibodies have remained negative. In a fourth child, the parents refused further examinations after antibody positivity was observed; the child has been without clinical manifestation of diabetes up until now. CONCLUSION: This scheme for predicting diabetes by means of immunogenetic and immunological examination of risk individuals is a rational measure aimed at timely identification of autoimmune insulitis, which precedes the occurrence of Type 1 diabetes, and it should become a standard part of diabetological care.

• MeSH
• autoprotilátky analýza   MeSH
• diabetes mellitus 1. typu diagnóza   genetika   MeSH
• genotyp MeSH
• glutamát dekarboxyláza imunologie   MeSH
• HLA-DQ antigeny genetika   MeSH
• insulinové protilátky MeSH
• izoenzymy imunologie   MeSH
• lidé MeSH
• novorozenec MeSH
• polymerázová řetězová reakce MeSH
• rizikové faktory MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• autoprotilátky MeSH
• glutamát dekarboxyláza MeSH
• glutamate decarboxylase 2 MeSH Prohlížeč
• HLA-DQ antigeny MeSH
• ICA512 autoantibody MeSH Prohlížeč
• insulinové protilátky MeSH
• izoenzymy MeSH