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Background:The association of apoptosis was analysed in three different compartments (foveolar cells- FC, proliferating zone-PZ and glandular part-GP) of antrum and corpus mucosa specimens with development of atrophy and the extent of apoptosis as depending on grade of chronic inflammation, activity of gastritis and Helicobacter pyloricolonization at two time points of an 18-year follow-up in an adult population from Saaremaa, Estonia, with a high prevalence of H. pyloriinfection were compared. Methods:A total of 68 persons (31 men, 37 women; median age, 39 years in 1979) from a primary sample of 304 subjects, endoscoped in 1979 and reinvestigated by endoscopy and biopsy in 1997, were included in the study. The state of the gastric mucosa and the presence of H. pyloriin the antrum and corpus mucosa were assessed in accordance with the Sydney system. The dynamics of apoptotic index (AI) between two time points in 1979 and 1997 was evaluated in antrum biopsies of 49 persons and in corpus biopsies of 64 persons. Apoptosis was measured using terminal deoxyuridine nucleotide nick end labelling (TUNEL) histochemistry. Results:The antrum as well as the corpus of 2/68 persons were H. pylorinegative at both time points. Atrophy developed in 9/68 persons in the antrum and in 23/68 in the corpus. In PZ and GP of the corpus mucosa as well as in GP of the antrum mucosa, AI decreased significantly during 18 years compared with initial values (P< 0.05), which was not associated with development of atrophy. In all compartments of the antrum and corpus mucosa, studied at the initial and end points of observation, AI did not reveal a difference in persons with and without development of atrophy (P> 0.05). In the samples of 1979 the highest independent effect on the value of AI in the FC compartment for the antrum was exerted by grade of activity of gastritis (P= 0.01) and in GP by degree of chronic inflammation (P= 0.03), while in the samples of 1997 the highest effec... [ABSTRACT FROM AUTHOR]

In 30% of H. pylori-infected patients a certain type of antigastric autoantibodies, reacting against canalicular structures within human parietal cells, is detectable. Furthermore, it has been shown that these autoantibodies are correlated with atrophy of the mucosa in the corpus. The aim of this study was to analyse the prevalence of these anticanalicular autoantibodies (ACAB) and their significance for development of gastric mucosa atrophy in a 12-year follow-up period. Gastric biopsy specimens from 62 persons in Saaremaa Island, Estonia, were collected in 1997 and assessed independently by two pathologists in accordance with the updated Sydney system. The sera of these persons were immunohistochemically screened for ACAB and for classic parietal cell antibodies (PCA). In addition, for 37 of the 62 persons, gastric biopsies and sera collected 12 years earlier (1985) were investigated in an analogous manner. ACAB increased significantly, from 8 out of 37 in 1985 to 17 out of 37 in 1997 (P=0.004; McNemar test). In 1997 a significant correlation existed between the presence of ACAB and corpus mucosa atrophy (19 out of 30 versus 10 out of 32 without atrophy; P=0.01; odds ratio (OR)=3.8, 95% CI 1.4-10.6). However, no correlation was found between ACAB and development of atrophy in the period from 1985 to 1997. All 37 persons were PCA negative in 1985, whereas in 1997, 2 turned out to be PCA positive. ACAB increased significantly with duration of H. pylori gastritis. The correlation between ACAB and presence of gastric corpus atrophy was confirmed. However, it is possible that ACAB are the consequence of and not a causative factor in gastric mucosa atrophy, insofar as the association of ACAB with progression of corpus atrophy was not significant. [ABSTRACT FROM AUTHOR]

Several authors have described an association between celiac disease (CD) and ulcerative colitis (UC), but this has not yet been established. The aim of our study was to examine the frequency of antigliadin antibodies (AGA), antireticulin antibodies (ARA) and antiendomysium (AEM) antibodies in the sera of patients with UC (n = 50), and to evaluate their correlation with clinical variables. Sixteen patients with irritable bowel syndrome (IBS) and 37 healthy individuals served as controls. An enzyme-linked immunosorbent assay was used for the detection of IgA- and IgG-type AGA. IgG-type ARA were determined by an indirect immunofluorescence assay (IIF) using rat kidney, liver, and stomach as antigen substrates. IgA-type AEM antibodies were measured by IIF, using cryostat sections from human umbilical cord. Seventeen of the 50 patients with UC (34%) were positive for IgA- or/and IgG-type AGA. There was no correlation between the presence of AGA and the duration or extent of the disease, or disease activity. However, 5 patients with both IgA- and IgG-types of AGA had extensive colitis. Only 2 controls (4%) were positive for IgG-AGA. ARA and AEM were not detected in any individuals studied. Since the ARA and AEM test results were negative, we conclude that none of the UC patients in this series had CD. [ABSTRACT FROM AUTHOR]

Evaluates the course of chronic gastritis and its association with Helicobacter pylori and CagA seroposivity. Correlation between intestinal metaplasia and gastritis; Effect of atrophy on epithelial cells; Prevalence of antibodies on CagA.

In the present study we used the highly sensitive avidin-biotin complex technique (ABC) for detection of gastrin cell (G cell) autoantibodies. Serum samples were studied from 56 patients with histologically proven antral gastritis, 20 adult subjects with histologically proven normal antral and fundal mucosa and from 25 healthy children. The presence of G cell autoantibodies was assessed by both immunofluorescence (IFL) and the A BC-peroxidase method, using sections from paraformaldehyde-lysine-periodate fixed and paraffin embedded human antral mucosa as antigen. Other organ specific and non-organ specifiic autoantibodies were demonstrated with IFL. Using the ABC method, G cell autoantibodies were found at a dilution of 1:100 in nine of 56 sera with antral gastritis. One of the control sera was positive. The ABC method was considered superior to IFL in demonstrating G cell antibodies, since positively stained G cells could be easily distinguished from the histiocytic cells in lamina propria which sometimes give false positive staining. Furthermore, higher antibody titres results in the ABC method. Thus it is suggested that by analogy to fundal gastritis, some cases of antral gastritis may have autoimmune aetiology. [ABSTRACT FROM AUTHOR]

Humoral and cellular immunity to a liver-specific membrane lipoprotein (LSP) was followed in rabbits immunized either with allogenic rabbit LSP (RLSP) or with xenogenic human (HLSP) or bovine (BLSP) antigens. After 4 months of immunization, all rabbits showed histoiogical changes in liver resembling those found in chronic aggressive hepatitis and occasionally also those seen in primary biliary cirrhosis in man. Antibodies reacting to both allogenic as well as xenogeneic LSP preparations were found with an enzyme-linked solid phase immunosorbents assay (F.LISA) in all immunized rabbits. Lymphocyte transformation tests in unionized rabbits showed an occasional response to some of the LSP preparations and a strong response towards an equivalent rabbit kidney preparation (RKSP). After immunization, reactions to LSP preparations increased significantly, while no response to RKSP was observed. The results confirm previous findings and further demonstrate that similar LSP containing preparations from human, bovine and rabbit sources share auto antigenic. liver-specific determinants. In addition, species specific determinants seem to be present in each of the LSP preparations studied. [ABSTRACT FROM AUTHOR]

Two groups of volunteers (199 in total, 149 of whom were a random sample of an urban population) were examined twice, with a 6-year interval, for the occurrence of parietal cell antibody (PCA) and thyroid microsomal antibodies (TMA). The antibody findings were compared with the antral and fundal gastric mucosal state, and with the fasting serum gastrin- 17 level. During the study period, two new PCA and four new TMA cases appeared. There were no significant changes in the state of gastric antral/fundal mucosa in relation to PCA and/or TMA persistence or appearance, as compared with the gastric mucosa changes in the whole random population sample. However, a good correlation was observed between PCA and basal serum gastrin elevation. [ABSTRACT FROM AUTHOR]

A sensitive enzymatic avidin-biotin complex technique was utilized to locate the antigenic sites in human liver which react with rabbit antibodies to human liver specific protein (LSP), Depending on the rabbit antiserum used, anti-LSP reactive material was seen in different locations. (1) diffusely distributed in liver parenchyma cells. (2) In both hepatocyte cytoplasm and plasma membrane and (3) in hepatocyte plasma membrane only. The cytoplasmic staining was partially or totally abolished by reabsorption with human kidney homogenate whilst the plasma membrane staining remained uninfluenced. The latter was apparently confined to bile canalicular walls and may be liver specific in contrast to the cytoplasmic reaction which seems to be due to antigen determinants cross-reacting with tissue components in kidney. [ABSTRACT FROM AUTHOR]

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the spontaneous destruction of the small intrahepatic bile ducts. The hallmark serologic feature of PBC is the presence of high-titer antimitochondrial antibodies (AMA). Both the incidence and prevalence of PBC varies geographically; epidemiological data may provide valuable insight regarding the pathogenic mechanisms and etiology of disease. Thus far, the majority of studies on the occurrence of PBC and AMAs have been derived from autopsy, mortality figures, or hospital admission records. The numbers reported reflect only those patients with clinical disease. To address this issue, an adult population sample representing all age groups in the village of Karksi-Nuia in southern Estonia was selected for a study of AMA incidence. This village has unique features that make it ideal for such a study. First, the village is remote and a substantial number of families have lived in the area for generations. There is also a limited influx of new families into the village, therefore providing a limited genetic repertoire. In this unselected adult population, we examined AMA incidence by both immunoblot and ELISA, using native and recombinant antigens. Of the 1461 people studied, 13 (0.89%) were AMA positive. A similar frequency (0.96%) was found among 104 persons from a neighboring village, who subsequently joined the study. Our study suggests that the presence of AMA in Estonia is in agreement with the reported incidence of less than 1% AMA in a mixed hospital population. [ABSTRACT FROM AUTHOR]

Background: Bile-tolerant Helicobacter spp. may be a risk factor for chronic liver diseases. Although data about the seroprevalence of antibodies to these Helicobacter spp. in adults are available, data about their presence in children are limited. Aim: To compare immune response to bile-tolerant Helicobacter spp. and H. pylori in children and in an adult population and in blood donors (Ananieva et al. IJMM 291; Suppl.31, G-06, 58, 2001). Methods: Sera from 103 consecutive paediatric patients (age range 1-14 y., 46 m, 57 f) were tested for IgG to the antigens of H. hepaticus (strain CCUG 33637), H. bilis (strain CCUG 38995), H. pullorum (strain CCUG 33838) and H. pylori (stain CCUG 17874) by ELISA. Results: The results are presented as the mean values of relative antibody activity (RAA). Immune response to H. pullorum and to H. bilis was significantly lower in children, wheras to H. hepaticus it was significantly higher in children, compared with the adults. A significantly higher mean value of RAA for H. hepaticus (29.7±26.9) and H. bilis (29.6±30.5) was in 1-5 y. children compared with those aged 6-10 y. (18.3±14.9 and 15.9±17.1; p = 0.03; p = 0.02). The mean RAA to H. pylori was significantly lower in children and in the youngest age group of 1-5 y.(16.5±21.7) compared with 11-14 y. (30.1±32.6; p = 0.04). Conclusion: Immune response to all Helicobacter spp. studied occurred in paediatric patients, while a significantly lower response to H. pullorum. H. bilis and H. pylori was established in children compared with adults. One can suppose that acquisition of H. hepaticus and H. bilis occur at age before 5 y. The cross-absorptions of sera and simultaneous identification of Helicobacter spp. in liver biopsies might be necessary for obtaining high immunoassay specificity. [ABSTRACT FROM AUTHOR]

Abstract Background Type 1 diabetes is a multifactorial disease with a strong genetic component. The aim of the study was to assess the impact of single nucleotide polymorphisms (SNPs) in several genes as susceptible markers in the risk of type 1 diabetes in the Estonian population. Methods: The rs6679677 (1p13), rs17696736 (12q24) and rs763361 (18q22) were genotyped in a total of 230 controls and 154 type 1 diabetes patients of Estonian origin. Results The rs6679677 A (OR = 2.13, 95%CI = 1.48-3.08, p = 0.00001), rs17696736 G (OR = 1.53, 95%CI = 1.14-2.04, p = 0.0046) and rs763361 T (OR = 1.48, 95%CI = 1.11-1.98, p = 0.0084) alleles were associated with risk of type 1 diabetes. Conclusions The current study supports the rs6679677 (PHTF1-PTPN22), rs17696736 (C12orf30) and rs763361 (CD226) SNPs as susceptibility factors for type 1 diabetes outside the major histocompatibility region (MHC) region. The full study had 80% or above to detect an odds ratio of 1.8 under the assumption of an additive model at type 1 error rate, α = 0.05.

Investigates the distribution of polymorphisms of HLA class-II and tumor necrosis factor molecules in patients with inflammatory bowel disease (IBD) in Estonia. Description of IBD; Use of reverse hybridization principle and sequence specific primers for HLA genotyping.

Background: Gestational diabetes mellitus (GDM) is the most prevalent metabolic disturbance during pregnancy and is associated with adverse outcomes in offspring, including an elevated risk for developing atopic diseases in early childhood. Research is limited regarding only women at risk of GDM among whom some develop GDM while others do not. Information about adverse health outcomes in the offspring of these women is also lacking. The main aim was to assess whether maternal GDM increases the offspring's risk of atopic dermatitis (AD), asthma and allergic rhinitis at 1, 2 and 5 years of age. The second aim was to analyze the association of other maternal health characteristics on the development of these disorders in offspring., Methods: The follow-up study group of the Gestational Diabetes Study (GDS), conducted at Tartu University Hospital, Estonia, between 2014 and 2020, comprised 223 mother-child dyads. All women had at least one risk factor for GDM, of whom only some developed GDM. Information about the diagnoses of interest was obtained from Electronic Health Records. Allergen-specific IgE from children's serum was measured using ImmunoCAP™ Phadiatop™ Infant, with results ≥ 0.35 kU/l considered positive. Statistical analysis was performed using the RStudio software (version 4.3.0)., Results: According to our results, only the cases of GDM requiring the use of antidiabetic medications were associated with the development of asthma and/or allergic rhinitis at 2 years of age (aOR 4.68, 95%CI 1.08-20.21, p = 0.039). Maternal obesity (BMI > 30) was associated with offspring´s asthma and/or allergic rhinitis diagnosis at 2 years of age (aOR 3.15, 95%CI 1.03-9.63, p = 0.045). Maternal abnormal weight gain during pregnancy was associated with asthma and/or allergic rhinitis at 5 years of age (aOR 2.76, 95%CI 1.04-7.31, p = 0.041)., Conclusion: Among pregnant women at risk for GDM, maternal weight-related factors significantly influence the development of atopic diseases in their children between 1 and 5 years of age, regardless of the GDM diagnosis. This suggests that, besides women with GDM greater attention should also be paid to women at risk but who do not develop GDM, as their children seem to be at higher risk of atopic diseases., (© 2024. The Author(s).)

Molecular mimicry has been proposed to be a possible mechanism of induction of autoimmunity. In some cases, it is believed that such events could lead to a disease such as Type 1 diabetes (T1D). One of the primary MHC-I epitopes in the non-obese diabetic (NOD) mouse model of T1D has been identified as a peptide from the islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) protein. In humans, the most common MHC-I model allele is HLA-A02; based on this, the study here identified a potential HLA-A0201-restricted human IGRP epitope as YLKTNLFLFL and also found a homologous A0201-restricted peptide in an Enterococcal protein. Using cells obtained from healthy human donors, it was seen that after a 2-week incubation with the synthetic bacterial protein, healthy A0201 + donor CD8 + cells displayed increased staining for human IGRP-peptide-dextramer. On the other hand, in control cultures, no significant levels of dextramer-staining CD8 + T-cells were detectable. From these outcomes, it is possible to conclude that certain bacterial proteins may initiate CD8 + T-cell-mediated immune reaction toward homologous human antigens.

Objectives: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA)., Methods: A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group "Autoimmunity Testing"; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP)., Results: In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations., Conclusions: These recommendations are an important step to achieve high quality ANA testing., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Introduction: Autoimmune diabetes occurs more often in the first 2 years of life in children with Down syndrome (DS) compared with the general population. We previously observed increased frequencies of islet autoantibodies, including insulin autoantibodies (IAA), in children with DS. Assays for IAA using 125 I-labelled insulin require competition to overcome cross reactivity with antibodies to the cow's milk protein, bovine serum albumin (BSA). 125 I-IAA assay results suggested that levels of antibodies to BSA may also be increased in children with DS. The aim of this study therefore was to determine whether the levels of anti-BSA antibodies differed in children with DS compared with controls., Methods: Samples were available from two populations with DS: one from the UK, (UK DS cohort n=106, 58 male, median age 12.5 years) and one from Estonia (Estonian DS cohort: n=121, 65 male, median age 9.75 years). A UK control population was provided by sex and age-matched healthy siblings of probands participating in the Bart's Oxford (BOX) family study of type 1 diabetes. A competitive-displacement radiobinding assay (RBA) and a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) were developed to measure and confirm anti-BSA antibody levels. HLA class II genotype was analysed by PCR using sequence specific primers (PCR-SSP)., Results: Overall, levels of anti-BSA antibodies were increased in those with DS compared with controls (p<0.0001) but this was not HLA associated., Conclusion: Increased levels of anti-BSA antibodies may reflect a defect in immune maturation or increased gut permeability in children with DS, increasing their risk of developing autoimmunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Grace, Mortimer, Kozhakhmetova, Leveret, Newton, Reimand, Shield, Uibo, Williams and Gillespie.)

Aims/introduction: We aimed to assess the distribution of transcription factor 7-like 2 gene TCF7L2 (rs7903146) polymorphism and to find possible associations between TCF7L2 and the characteristics of type 1 diabetes., Materials and Methods: We studied 190 newly diagnosed type 1 diabetes patients (median age 12.7 years, range 2.0-72.5) and 246 controls (median age 23.8 years, range 1.4-81.5) for TCF7L2 single nucleotide polymorphism. We determined anti-islet autoantibodies, random C-peptide levels, diabetes associated HLA DR/DQ haplotypes and genotypes in all patients., Results: There were no differences in the distribution of TCF7L2 single nucleotide polymorphism between patients and controls. However, patients with in type 1 diabetes, after adjusting for age and sex, subjects carrying C allele were at risk for a C-peptide level lower than 0.5 nmol/L (OR 5.65 [95% CI: 1.14-27.92]) and for zinc transporter 8 autoantibody positivity (5.22 [1.34-20.24]). Participants without T allele were associated with a higher level of islet antigen-2 autoantibodies (3.51 [1.49-8.27]) and zinc transporter 8 autoantibodies (2.39 [1.14-4.99])., Conclusions: The connection of TCF7L2 polymorphism with zinc transporter 8 and islet antigen-2 autoantibodies and C-peptide levels in patients supports the viewpoint that TCF7L2 is associated with the clinical signs and autoimmune characteristics of type 1 diabetes. The mechanisms of the interaction between the TCF7L2 risk genotype and anti-islet autoantibodies need to be studied further., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: In coeliac disease (CoD), the role of B-cells has mainly been considered to be production of antibodies. The functional role of B-cells has not been analysed extensively in CoD., Methods: We conducted a study to characterize gene expression in B-cells from children developing CoD early in life using samples collected before and at the diagnosis of the disease. Blood samples were collected from children at risk at 12, 18, 24 and 36 months of age. RNA from peripheral blood CD19 + cells was sequenced and differential gene expression was analysed using R package Limma., Findings: Overall, we found one gene, HNRNPL , modestly downregulated in all patients (logFC -0·7; q = 0·09), and several others downregulated in those diagnosed with CoD already by the age of 2 years., Interpretation: The data highlight the role of B-cells in CoD development. The role of HNRPL in suppressing enteroviral replication suggests that the predisposing factor for both CoD and enteroviral infections is the low level of HNRNPL expression., Funding: EU FP7 grant no. 202063, EU Regional Developmental Fund and research grant PRG712, The Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research (SyMMyS) 2012-2017, grant no. 250114) and, AoF Personalized Medicine Program (grant no. 292482), AoF grants 292335, 294337, 319280, 31444, 319280, 329277, 331790) and grants from the Sigrid Jusélius Foundation (SJF)., Competing Interests: The authors declare no competing interests., (© 2023 The Authors. Published by Elsevier Ltd.)

Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (P < 5 × 10-8) with GDM, mapping to/near MTNR1B (P = 4.3 × 10-54), TCF7L2 (P = 4.0 × 10-16), CDKAL1 (P = 1.6 × 10-14), CDKN2A-CDKN2B (P = 4.1 × 10-9) and HKDC1 (P = 2.9 × 10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomization analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy., (© The Author(s) 2022. Published by Oxford University Press.)

Aims/introduction: Gestational diabetes (GDM) is characterized by low-grade systemic inflammation, which manifests as changes in the levels of cytokines in the blood. We aimed to investigate plasma immune mediators during gestational weeks 23-28 in 213 women at risk for GDM, and to find associations between GDM and its complications., Materials and Methods: We quantified the levels of adipokines: adiponectin, leptin, plasminogen activator inhibitor-1 and resistin; chemokines: C-C motif chemokine ligand 2 (CCL2), CCL4, C-X-C motif chemokine ligand 8 (CXCL8) and CXCL10; and cytokines: granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1β, soluble (s)IL-1RI, IL-2, sIL-2Ra, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12(p70), IL-13, IL-15, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-27, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, tumor necrosis factor-α and soluble tumor necrosis factor receptor 2 using the Milliplex®MAP Magnetic Bead assay on Luminex®200™, and compared the results with clinical data from pregnancy and post-partum follow up., Results: Lower levels of adiponectin and higher levels of CCL2 (Wilcoxon test, P = 3.4E-03 and P = 0.03, respectively) were found in women with GDM. IL-27 levels were associated with lower odds of GDM (adjusted logistic regression 0.90, P = 2.4E-03), and showed a risk association with glutamic acid decarboxylase autoantibody positivity (adjusted odds ratio 1.13, P = 2.8E-03). Similarly, higher IL-22 levels increased the odds of glutamic acid decarboxylase autoantibody positivity (adjusted odds ratio 4.23, P = 0.04). TGF-β1 was associated with post-partum fasting glucose levels, and CCL4 with post-partum C-peptide levels (linear regression, P = 0.04 and P = 0.01, respectively). Women who developed pregnancy complications had higher levels of CXCL10 and CCL4 (linear regression, P = 7.0E-04 and P = 0.01, respectively)., Conclusions: Plasma adiponectin and CCL2 concentrations distinguish women with GDM. IL-27 and IL-22 levels might select women with an autoimmune reaction, whereas increased TGF-β1 and CCL4 are associated with post-partum glucose and insulin metabolism., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Enteroviruses (EV) are among the leading environmental triggers of childhood-onset type 1 diabetes (T1D). Our aim was to determine the prevalence of antibodies against EV and their association with T1D in different age groups ( n = 62), including young adults, and to compare these data with results from HLA-matched control participants ( n = 62). IgA, IgG, and IgM antibodies against EV were detected. IgA EV antibodies were present in 46.8% of participants with T1D (median level 10.9 EIU) and in 11.3% of controls (median level 3.4 EIU). IgA EV positivity and higher level of IgA EV antibodies were both significant risk factors for T1D (odds ratio (OR) 8.33; 95% confidence interval (CI) 2.52-27.6; p = 0.0005 and OR 1.04; 95% CI 1.01-1.06; p = 0.0105, respectively). Importantly, the prevalence of IgA EV antibodies in the subgroups of both children and young adults was also significantly different between participants with T1D and their matched controls ( p = 0.0089 and p = 0.0055, respectively). Such differences were not seen for IgG and IgM EV antibodies. However, IgG EV antibodies were associated with 65 kDa glutamic acid decarboxylase antibodies, but not with zinc transporter 8 and protein tyrosine phosphatase IA2 antibodies. The genotype frequency of PTPN22 (rs2476601) and IFIH1 (rs1990760) was not associated with EV positivity. This study showed that EV infections may be an important disease-promoting factor of T1D not only in childhood-onset but also in adult-onset T1D. However, to further confirm this association, direct virological studies are needed in the latter T1D group., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Kristi Alnek et al.)