Autoimmune Diseases In Children Research Articles

Inflammasomes and Childhood Autoimmune Diseases: A Review of Current Knowledge.

Inflammasomes are multiprotein complexes capable of sensing pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and cellular perturbations. Upon stimulation, the inflammasomes activate the production of the pro-inflammatory cytokines IL-1β and IL-18 and induce gasdermin D-mediated pyroptosis. Dysregulated inflammasome signaling could lead to hyperinflammation in response to environmental triggers, thus contributing to the pathogenesis of childhood autoimmune/autoinflammatory diseases. In this review, we group childhood rheumatic diseases into the autoinflammation to autoimmunity spectrum and discuss about the involvement of inflammasomes in disease mechanisms. Genetic mutations in inflammasome components cause monogenic autoinflammatory diseases, while inflammasome-related genetic variants have been implicated in polygenic childhood rheumatic diseases. We highlight the reported associations of inflammasome signaling-related genetic polymorphisms/protein levels with pediatric autoimmune disease susceptibility and disease course. Furthermore, we discuss about the use of IL-1 receptor antagonist as an adjunctive therapy in several childhood autoimmune diseases, including macrophage activation syndrome (MAS) and multisystem inflammatory syndrome in children (MIS-C) related to COVID-19. A comprehensive multi-cohort comparison on inflammasome gene expression profile in different pediatric rheumatic diseases is needed to identify patient subsets that might benefit from the adjunctive therapy of IL-1β inhibitors.

Identification of the Key Genes Involved in the Effect of Folic Acid on Endothelial Progenitor Cell Transcriptome of Patients with Type 1 Diabetes.

Type 1 diabetes (T1D) is one of the most common autoimmune diseases in children. Previous studies have suggested that endothelial progenitor cells (EPCs) might be engaged in the regulating of the biological processes in T1D and folic acid (FA) might be engaged in regulating EPC function. The present study has identified 716 downregulated genes and 617 upregulated genes in T1D EPC cases after treated with FA. Bioinformatics analysis has shown that these DEGs were engaged in regulating metabolic processes, cell proliferation-related processes, bone marrow development, cell adhesion, platelet degranulation, and cellular response to growth factor stimulus. Furthermore, we have conducted and identified hub PPI networks. Importantly, we have identified 6 upregulated genes (POLR2A, BDNF, CDC27, LTN1, RAB1A, and CUL2) and 8 downregulated genes (SHC1, GRIN2B, TTN, GNAL, GNB2, PTK2, TF, and TLR9) as key regulators involved in the effect of FA on endothelial progenitor cell transcriptome of patients with T1D. We think that this study could provide novel information to understand the roles of FA in regulating EPCs of T1D patients.

Clinical Features of Acute Rhabdomyolysis in 55 Pediatric Patients.

Objective: This study was designed to compare the clinical manifestations, laboratory tests, etiology, and prognosis of children with acute rhabdomyolysis (RM) at various ages. This study was designed to analyze the risk factors for acute kidney injury (AKI) in children with RM and to identify the role of neuromuscular and autoimmune disease in children with RM.Methods: Clinical data for 55 children with RM were collected and statistically analyzed. Patients were stratified to an infant group (G1) (age <1 year), preschool group (G2) (age 1–6 year), school-age group (G3) (age 7–11 year), and an adolescent group (G4) (age 12–16 year).Results: The top three clinical manifestations were dark urine (52.7%), myalgia (38.2%), and fever (23.8%). Patients in G1 had fever (71.4%), vomiting (77.8%), and urinalysis abnormalities (14.3%), without triad clinical manifestations. Fifty percent of patients in G4 group had myalgia; 70.8% had dark urine; 75% had abnormal urine tests. The most common cause in each age group was as follows: sepsis (57.1%) in G1; hereditary neuromuscular diseases (44.4%) in G2; immune diseases (40%) in G3; strenuous exercise (50%) in G4. Logistic regression analysis shown that AKI was not corelated with age, gender, or peak creatine phosphokinase. AKI was, however, associated with presence of an electrolyte disorder.Conclusion: The clinical manifestations and laboratory findings in infants with acute RM are not typical and need to be taken seriously. The presence of an electrolyte disorder is a risk factor for AKI in children with RM. The most common pathogenesis of RM varies among age groups. Congenital hereditary metabolic disease and immune diseases should not be ignored as a cause of RM in children.

Prediction and Prevention of Type 1 Diabetes.

Type 1 Diabetes (T1D) is one of the most common chronic autoimmune diseases in children. The disease is characterized by the destruction of beta cells, leading to hyperglycemia, and to a lifelong insulin-dependent state. Although several studies in the last decades have added relevant insights, the complex pathogenesis of the disease is not yet completely understood. Recent studies have been focused on several factors, including family history and genetic predisposition (HLA and non-HLA genes) as well as environmental and metabolic biomarkers, with the aim of predicting the development and progression of T1D. Once a child becomes symptomatic, beta cell mass has already reached a critical threshold (usually a residual of 20–30% of normal amounts), thus representing only the very late phase of the disease. In particular, this final stage follows two preceding asymptomatic stages, which have been precisely identified. In view of the long natural history and complex pathogenesis of the disease, many strategies may be proposed for primary, secondary, and tertiary prevention. Strategies of primary prevention aim to prevent the onset of autoimmunity against beta cells in asymptomatic individuals at high risk for T1D. In addition, the availability of novel humoral and metabolic biomarkers that are able to characterize subjects at high risk of progression, have stimulated several studies on secondary and tertiary prevention, aimed to preserve residual beta cell destruction and/or to prolong the remission phase after the onset of T1D. This review focuses on the major current knowledge on prediction and prevention of T1D in children.

Association Between Severity of Diabetic Ketoacidosis at Diagnosis and Multiple Autoimmunity in Children With Type 1 Diabetes Mellitus: A Study From a Greek Tertiary Centre

ObjectivesType 1 diabetes mellitus is a chronic disorder associated with development of autoimmunity. In this work, we studied the relationship between severity of acidosis at diagnosis and future risk for autoimmunity development in children with type 1 diabetes. MethodsWe investigated the presence of associated autoimmunity in 144 children with type 1 diabetes (mean ± standard deviation: age, 12.44±4.76 years; diabetes duration, 4.41±3.70 years). We identified the presence of thyroid disease, celiac disease, autoimmune gastritis and adrenal autoimmunity, and retrospectively reviewed the files for presence of diabetic ketoacidosis at diagnosis. ResultsAutoimmunity prevalence was 16.7% for thyroid autoimmunity, 9.5% for celiac disease, 5% for gastric autoimmunity and 8.0% for multiple autoimmunities. There were strong associations between severe acidosis at diabetes diagnosis (pH<7.10) and development of thyroid autoimmunity (odds ratio [OR], 5.34; 95% confidence interval [CI], 1.90‒15.1; p<0.001), celiac disease (OR, 5.83; 95% CI, 1.19‒28.6; p=0.013), gastric autoimmunity (OR, 13.1; 95% CI, 1.22‒140; p=0.006) and multiple autoimmunity (OR, 26.7; 95% CI, 2.36‒301; p<0.01). The associations persisted after adjustment for sex, age at diabetes diagnosis, age at assessment, time since diabetes diagnosis and antiglutamic acid decarboxylase autoantibody status. ConclusionsThe severity of acidosis at diagnosis is strongly associated with the development of associated autoimmune diseases in children with type 1 diabetes and could act as a predictive factor for multiple autoimmunity development. This association can be either due to effect of acidosis on immune system or to the presence of a more aggressive diabetes endotype.

Autoimmune associations of alopecia areata in pediatric population - A study in tertiary care centre

Alopecia areata (AA) is second most common disease leading to non scarring alopecia . It occurs in many patterns and can occur on any hair bearing site of the body. Many factors like family history, autoimmune conditions and environment play a major role in its etio-pathogenesis. Histopathology shows bulbar lymphocytes surrounding either terminal hair or vellus hair resembling "swarm of bees" appearance depending on chronicity of alopecia areata. Alopecia areata in children is frequently seen. Pediatric AA has been associated with atopy, thyroid abnormalities and a positive family history. We have done a study to find out if there is any association between alopecia areata and other auto immune diseases in children. This study is an observational study conducted in 100 children with AA to determine any associated autoimmune conditions in them. SALT score helps to assess severity of alopecia areata. Severity of alopecia areata was assessed by SALT score-1. S1- less than 25% of hairloss, 2. S2- 25-45% of hairloss, 3. 3.S3- 50-74% of hairloss.

Children with chronic-refractory autoimmune cytopenias: a single center experience.

Autoimmune cytopenias are a group of heterogeneous disorders characterized by immune-mediated destruction of one or more hematopoietic lineage cells. The differential diagnosis of children with autoimmune cytopenias requires much time and laboratory investigations. The aim of the present study was to evaluate the clinical course and significance of autoimmune cytopenias due to immunodeficiency or autoimmune diseases in children at a single children`s hospital. Between February 1997 and September 2015, chronic/refractory autoimmune cytopenias patient data were evaluated retrospectively. Twenty-three patients were assessed in this study. The median duration of following was 2.6 years (4 months-18.5 years). The median age of diagnosis was 3.1 years (6 months-16 years). A total of 13 patients (56.5%) had single-lineage and 10 (46.5%) had multilineage cytopenias. The most frequent single-lineage cytopenia was thrombocytopenia, followed by anemia. In 22 of the patients, cytopenias was detected before the primary diseases. All of the patients were treated with corticosteroids or intravenous immune globulin as first-line treatment. Ten patients (43.5%) needed second or further-line immunosuppressive therapies that patients diagnosed as systemic lupus erythematosus, hypogammaglobulinemia, or common variable immunodeficiency. A total of 8 patients (34.7%) recovered from autoimmune cytopenias after the treatment of primer disease. Cytopenias were continued in 14 patients. Cytopenia may be the first finding of an immunodeficiency or autoimmune disease and primary disease may be diagnosed in the clinical course. Taking the new targeted treatment options into consideration; early diagnosis is likely to become more important in the near-future in order to begin the treatment for the underlying disease as early as possible.

Peripheral Blood B and T Cell Profiles in Children with Active Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is one of the most common autoimmune diseases in children. Our study aimed to evaluate the peripheral blood B and T lymphocyte subpopulations in children with JIA. This case-control study included 20 children with JIA as well as 20 healthy children with matching age and sex as a control group. All patients included in the study were in activity as determined by visual analog scale. In addition to complete clinical evaluation, basic investigations, peripheral blood B and T lymphocyte subpopulations were done to all participants by flow cytometry. JIA patients displayed a significant decrease in IgM memory B lymphocytes, switched memory B lymphocytes, and total memory B lymphocytes when compared to the healthy controls. The percentages of naïve B lymphocytes were significantly increased in JIA patients than in controls. Total T lymphocytes, CD8+CD28null cells, and CD4+CD28null cells were significantly increased in JIA patients as compared to controls. In conclusion; JIA patients have an alteration in both B and T lymphocytes with the predisposition of memory cells which may have a role in sustaining the JIA disease activity.

Investigation of Autoimmune Disease in Children with Chronic Spontaneous Urticaria

Introduction: Chronic spontaneous urticaria (CSU) in childhood affects the quality of life of the patient and may be associated with other autoimmune diseases. The aim of this study was to investigate the association of autoimmune diseases with CSU in children. Methods: In a 3-year period, from 2015 to 2018, forty-nine children were diagnosed with CSU and monitored in the Outpatient Pediatric Allergy Clinic of the University Hospital of Ioannina in Northwestern Greece. The comorbidity with other autoimmune diseases was investigated in this population by autoantibody evaluation. Results: Of the 49 children with CSU, 1 had autoantibodies for celiac disease (CD), which was confirmed by duodenal biopsy via gastroscopy. Four children had high serum levels of anti-thyroid peroxidase antibodies but normal thyroid function. No other specific autoantibodies were detected. Conclusion: The prevalence of autoimmune diseases among our children with CSU was low. Nevertheless, we think it is important to test children with CSU for other autoimmune diseases. CD can be diagnosed in children with CSU even in the absence of other indicative signs.

Su1441 – Association of Autoimmune Diseases in Children with Acute Recurrent Or Chronic Pancreatitis

Su1441 – Association of Autoimmune Diseases in Children with Acute Recurrent Or Chronic Pancreatitis

Long-term evolving profile of childhood autoimmune blistering diseases: Retrospective study on 38 children.

Autoimmune bullous dermatoses (AIBDs) in children are uncommon, and their long-term evolution remains unknown. The aim of this retrospective study was to characterize the long-term prognosis of AIBDs that started during childhood. We conducted a monocentric retrospective study, in the French dermatology centre, by including all children affected by AIBDs. The long-term outcome was obtained through a phone call questionnaire. Sixty-three patients were included from January 1993 to December 2015, 34 female and 29 males: 27 Linear immunoglobulin A disease (LAD), 12 bullous pemphigoid (BP), 12 pemphigus, 8 herpetiform dermatitis (DH) and 4 epidermolysis bullosa aquisita (EBA). The mean age was 4.7years old. Twenty-five patients were lost during the follow-up. For the 38 remaining patients, the mean follow-up duration for all pathologies was 6.6years. Twenty-nine of them had at least one relapse. Late relapses were observed in two cases of DH and six cases of pemphigus (7-34months). The mean treatment duration was 30.6months with variability according to the AIBDs. Topical corticosteroids were used alone, effectively, for seven patients and in association with other treatment in 19 patients in complete remission. Complete remission was noted in 34/38 children with a follow-up of 4.4years (0.08-19.5). The mean duration to complete remission was 30.5months (6-114months). Late nasal synechiae were reported in one EBA only. There was no significant associated comorbidity, but an association with a primary immune deficiency (PID) was observed in two cases. Childhood AIBDs appear to be of good overall prognosis but a long-term follow-up is mandatory, as relapses can be late, except for BP. The use of topical corticosteroids is frequently effective alone or in association. The association with PID leads to think about the possibility of a possible underlying dysimmunity in the child.

Autoimmune Markers in Children with Chronic Immune Thrombocytopenia

Introduction: Chronic immune thrombocytopenia (ITP) is defined as isolated thrombocytopenia lasting longer than 12 months. Rheumatologic diseases, immunodeficiencies and thyroid diseases may coexist with chronic ITP due to possible immune dysregulation.Aim: To evaluate the accompanying autoimmune diseases in children with chronic ITP.Materials-Methods: A total of 154 children with chronic ITP (F /M: 1) diagnosed between 1995 and 2018 were included. Patients were evaluated with immunoglobulin levels, ANA, anti dsDNA, C3, C4, anti TPO, anti TG, T4, TSH, tissue transglutaminase IgA and Ig G.Results: Of the 154 patients, 79 were female (51.3%) and 75 were male (48.7%). Mean age of the patients was 13.6 ± 5.8 years, mean age of diagnosis was 7 years ± 4. None of the patients had severe infections requiring hospitalisation. None of the patients had symptoms or findings of an autoimmune disorder. Of 154, two had low IgA levels (<7 mg / dL) and they were diagnosed as IgA deficiency. IgM and IgG levels were normal in all. C3 level was low in four patients (3%) and C4 level was low in one patient (0.7%). ANA was positive in 16 (12%) of the patients and anti-dsDNA was positive in four patients (0,3%). In three patients, Anti-dsDNA positivity was accompanied with ANA positivity and in one patient, C3 was low. These patients were followed up by pediatric rheumatology clinic. Twenty two patients had elevated anti TPO (15.5%) and 18 patients had elevated anti TG (12.7%) levels. Majority of patients with high thyroid autoantibodies were female (67.5%). Out of 129 patients evaluated by thyroid tests including fT4, TSH, AntiTPO and AntiTG, 29 (% 22,4) were diagnosed as Hashimoto thyroiditis. Thyroid hormone replacement was started in one patient . Of 93 patients evaluated with anti-tissue transglutaminases, 7 were found to have at least one positive TTG IgA or IgG. Two of these patients underwent endoscopy, but no evidence of celiac disease was found. In total, the number of patients with at least onepositive autoimmune marker was 54 (35%).Discussion and Conclusion: Chronic ITP is known to accompany autoimmune diseases. Autoimmune diseases in patients with ITP may occur at any time in 10 years of diagnosis. Further studies for the detection of subclinical autoimmune conditions should be performed with a profit- loss account. Antibodies may be positive even when there is no clinical findings of the diseases. Further follow-up is needed to understand the clinical significance of autoimmune markers in chronic ITP. DisclosuresNo relevant conflicts of interest to declare.

Association between atopic dermatitis and autoimmune disorders in US adults and children: A cross-sectional study

Little is known about the risk and predictors of autoimmune diseases in children and adults. To determine the prevalence, predictors, and excess costs of autoimmune disease in atopic dermatitis (AD) patients. Cross-sectional study of the 2002-2012 National Inpatient Sample, which includes a ∼20% sample of all US hospitalizations (n=87,053,155 adults and children). The prevalence of autoimmune disease was higher in adults with AD (7.9%, 95% confidence interval [95% CI] 7.3-8.5%) than without AD (5.7%, 95% CI 5.7%-5.8%) and higher in children with AD (2.0%, 95% CI 1.7%-2.3%) than without AD (1.0%, 95% CI 0.9%-1.1%). In multivariable logistic regression models controlling for sociodemographics, adult (adjusted odds ratio 1.45, 95% CI 1.32-1.58) and pediatric (adjusted odds ratio 2.08, 95% CI 1.73-2.50) AD were associated with any autoimmune disorder. In particular, AD was associated with 18 of 32 autoimmune disorders examined in adults and 13 of 24 examined in children, including disorders of the skin, endocrine, gastrointestinal, hematologic, and musculoskeletal systems. AD patients hospitalized with any autoimmune disorder had a higher cost of inpatient care, with $2.5-$50 million excess annual costs. Adults and children with AD had increased cutaneous and extracutaneous autoimmune disorders, which were associated with a considerable cost burden.

Impact of Thyroid Autoimmunity on Thyroid Function in 12-year-old Children With Celiac Disease.

Celiac disease (CD) is associated with thyroid autoimmunity and other autoimmune diseases. Data are, however, lacking regarding the relationship between thyroid autoimmunity and thyroid function, especially in regard to CD. Our aim was to investigate the impact of thyroid autoimmunity on thyroid function in 12-year-old children with CD compared to their healthy peers. A case-referent study was conducted as part of a CD screening of 12-year-olds. Our study included 335 children with CD and 1695 randomly selected referents. Thyroid autoimmunity was assessed with antibodies against thyroid peroxidase (TPOAb). Thyroid function was assessed with thyroid-stimulating hormone and free thyroxine. TPOAb positivity significantly increased the risk of developing hypothyroidism in all children. The odds ratios (with 95% confidence intervals) were 5.3 (2.7-11) in healthy 12-year-olds, 10 (3.2-32) in screening-detected CD cases, 19 (2.6-135) in previously diagnosed CD cases, and 12 (4.4-32) in all CD cases together. Among children with TPOAb positivity, hypothyroidism was significantly more common (odds ratio 3.1; 95% CI 1.03-9.6) in children with CD (10/19) than in children without CD (12/46). The risk of thyroid dysfunction due to thyroid autoimmunity is larger for those with CD than their healthy peers. Our study indicates that a gluten-free diet does not reduce the risk of thyroid dysfunction. Further studies are required for improved understanding of the role of the gluten-free diet for the risk of autoimmune diseases in children with CD.

Prevalence of β-cell antibodies and associated autoimmune diseases in children and adolescents with type 1 diabetes (T1DM) versus type 2 diabetes (T2DM) in Qatar.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease with the development of abnormal immune responses to specific β-cell autoantigens in addition to other organ-specific autoimmunity. The most frequent associated disorders are thyroid dysfunctions and celiac disease. There are limited studies in the current literature on the prevalence of associated autoimmunity, especially multiple, in children and adolescents with T1DM and Type 2 diabetes mellitus (T2DM). The aim of the present study was to determine the prevalence of autoantibodies and thyroid dysfunctions in a cohort of children and adolescents (aged 0.5-16 years) with T1DM living in Qatar. The records of all children and adolescents attending the Pediatric Diabetes Center of Hamad Medical Center, for the past 5 years (from January 2012 to December 2016), were reviewed and all clinical and biochemical data, including β-cell autoimmunity [anti-glutamic acid decarboxylase (GAD) antibodies, anti-islet cell and anti-insulin antibodies (IAA)], thyroid function (Free thyroxine: FT4 and thyroid-stimulating hormone: TSH), anti-thyroid peroxidase antibodies (TPO) and anti-tissue transglutaminase (ATT) were collected at their first presentation (cross-sectional study). Data for patients with T1DM (n=431) and T2DM (n=59) were recorded analyzed and the prevalence calculated and compared with other studies. The prevalence of anti-GAD antibodies was 75.5 % in T1DM and 29.3% in T2DM. Anti β-islet antibodies (Ab) were detected in 53.4% of T1DM and 29.4% of T2DM. Anti-insulin Ab were detected in 40.4% of T1DM and 58.3% of T2DM. The three antibodies together were detected in 18.4 % of T1DM and none of T2DM. At presentation, hypothyroidism (FT4 <11.5 pmol/L) was detected in 10.6% of T1DM and 10% of T2DM. Subclinical hypothyroidism was diagnosed in 3.5% of T1DM and 8% of T2DM. High anti TPO was detected in 27.2% of T1DM and 34.6% of T2DM. High TPO with normal thyroid function were found in 22.7% of T1DM and 23.1% of T2DM. ATT IgA was high in 5% of T1DM and 8.7% of T2DM whereas ATT IgG was high in 4.4 % of T1DM and not detected in any patient with T2DM. Mucosal biopsy proved celiac disease in 9 out of 12 patients (75%) with positive ATT IgA and IgG antibodies. Qatar has a relatively high incidence of T1DM compared to incidences reported worldwide. The incidence increased over the period 2012-2015. We report a high prevalence of associated autoimmune abnormalities in our patients with T1DM and T2DM. These data strengthen the argument for routine screening of all children and adolescents with T1DM and T2DM for other autoimmune disorders, particularly the thyroid gland.

Аутоімунні захворювання у дітей з первинними дефіцитами антитілоутворення

Аутоімунні захворювання у дітей з первинними дефіцитами антитілоутворення

Prevalence of Family History of Autoimmune Disorders in Juvenile Systemic Lupus Erythematosus

One of the causes of infants' hospitalizations is bronchiolitis, while different viral agents could be causative agents. As there is little information regarding the common agents of bronchiolitis in Iranian infants, we designed this study to determine which agents were responsible for hospitalization due to bronchiolitis among infants in an Iranian tertiary center. Two hundred and three infants with bronchiolitis who were hospitalized in Bahrami hospital were enrolled. Data regarding age, sex, duration of hospitalization, exposure to smoking, previous antibiotic usage and fever were collected for all enrolled cases. Throat sample by means of soap was collected and rapid test with immunochromatography (IC) test was performed. Rapid test was positive in 59 (29%) cases and three cases had concomitant infection with two viruses. The most common viral agent was RSV (Respiratory Syncytial Virus). Mean age was significantly lower in cases with RSV or RSV+ adenovirus infectious in comparison with other two groups (adenovirus or influenza only), while mean duration of hospitalization was significantly longer in RSV/RSV+ adenovirus group. RSV is the most common viral etiology of bronchiolitis in Iranian infants less than one year old, which is related with younger age and longer duration of hospitalization. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Near 10% of affected children have a relative with SLE. Autoimmune diseases are more common in relatives of children with SLE. As there is no study regarding the prevalence of autoimmune disease in cases with pediatric SLE, we designed this study to evaluate the prevalence of autoimmune disease in children with SLE. In this cross sectional study, 50 children with SLE and 50 healthy children were enrolled. A structured questionnaire was used to collect data regarding the presence of autoimmune diseases in relatives. One thousand eight hundred and thirty two relatives were evaluated in the case group and 1699 in the control group. The number of relatives with autoimmune diseases was significantly higher in the case group (26 vs 10). The most common autoimmune diseases were lupus, followed by thyroid diseases among cases, and thyroid diseases and rheumatoid arthritis in controls. According to the results of this study, the prevalence of autoimmune disorders is more common in relatives of children with SLE than in those of controls.

Аутоиммунные заболевания у детей с приобретенной апластической анемией

Аутоиммунные заболевания у детей с приобретенной апластической анемией

HLA and non-HLA genes and familial predisposition to autoimmune diseases in families with a child affected by type 1 diabetes.

Genetic predisposition could be assumed to be causing clustering of autoimmunity in individuals and families. We tested whether HLA and non-HLA loci associate with such clustering of autoimmunity. We included 1,745 children with type 1 diabetes from the Finnish Pediatric Diabetes Register. Data on personal or family history of autoimmune diseases were collected with a structured questionnaire and, for a subset, with a detailed search for celiac disease and autoimmune thyroid disease. Children with multiple autoimmune diseases or with multiple affected first- or second-degree relatives were identified. We analysed type 1 diabetes related HLA class II haplotypes and genotyped 41 single nucleotide polymorphisms (SNPs) outside the HLA region. The HLA-DR4-DQ8 haplotype was associated with having type 1 diabetes only whereas the HLA-DR3-DQ2 haplotype was more common in children with multiple autoimmune diseases. Children with multiple autoimmune diseases showed nominal association with RGS1 (rs2816316), and children coming from an autoimmune family with rs11711054 (CCR3-CCR5). In multivariate analyses, the overall effect of non-HLA SNPs on both phenotypes was evident, associations with RGS1 and CCR3-CCR5 region were confirmed and additional associations were implicated: NRP1, FUT2, and CD69 for children with multiple autoimmune diseases. In conclusion, HLA-DR3-DQ2 haplotype and some non-HLA SNPs contribute to the clustering of autoimmune diseases in children with type 1 diabetes and in their families.

THE ASSOCIATION OF CELIAC DISEASE WITH OTHER AUTOIMMUNE DISEASES IN CHILDREN

Celiac disease (CD) is an autoimmune disease with estimated prevalence of 1% in European and North American population. All four components of CD autoimmunity are well known, such as: genetics, autoantigen, autoantibodies and the environmental triggers. Besides gastrointestinal manifestations, celiac disease has a wide array of extraintestinal symptoms and clinical signs. This article briefly summarizes celiac disease pathophysiology and association of celiac disease with other autoimmune diseases in children. It puts emphasis on possible protective role of gluten-free diet for the development of other autoimmune diseases in patients with celiac disease.