ABSTRACT
The alternative pathway of complement plays an important role in the pathogenesis of coeliac disease (CD), where factor B (BF) is central to its activation. CD is a gluten-sensitive enteropathy that results from a complex interplay between genetic, immunologic, and environmental factors. In this study we evaluated the association of BF allotypes with the susceptibility and severity of CD, and with the presence of autoantibodies. Seventy-six non-related patients (56 female; 20 male; 2-77 years) and 150 first-degree relatives (87 female, 63 male; 2-75 years) were investigated. As controls, 97 healthy individuals were included (67 female;, 30 male; 1-71 years). The BF allotypes were determined by high-voltage agarose gel electrophoresis, followed by specific immunofixation. Disease severity was evaluated by anti-endomisial antibody (IgA-EmA) titres and histological findings of intestinal mucosa, which showed a high correlation (r = 0.8; P < 0.00001) in samples collected simultaneously. IgA-EmA was detected in all CD patients ingesting gluten, and in 13.3% of the relatives. The IgA-EmA, smooth muscle, mitochondrial, liver-kidney microsomal, nuclear, gastric parietal cells, and thyroid microsome antibodies were tested by indirect immunofluorescence. A significant decrease in BF S (P = 0.026) and an increasing tendency in BF SF allotype (P = 0.06) were observed in CD patients when compared to their relatives. On the other hand, BF S frequency was increased (P = 0.001 RR = 2.32) and BF SF (P = 0.002) decreased in the relatives when compared to the controls. No differences were observed in the distribution of BF phenotypes amongst the CD patients and the control group, and no association was found with CD severity or with the presence of autoantibodies. These results suggest BF SF as a CD susceptibility marker, and BF S as a protection marker of the disease amongst CD families in the Brazilian population.
Subject(s)
Celiac Disease/genetics , Complement Factor B/genetics , Genetic Predisposition to Disease/genetics , Adolescent , Adult , Aged , Biomarkers , Brazil , Celiac Disease/immunology , Celiac Disease/pathology , Child , Child, Preschool , Complement Factor B/immunology , Family , Female , Humans , Male , Middle Aged , Phenotype , Severity of Illness IndexABSTRACT
The coexistence of celiac disease together with a range of autoimmune disorders has already been reported. The aims of this study were to perform a broad spectrum of autoantibodies in celiac patients (N = 56), their first-degree relatives (N = 118), and compare the data with healthy controls (N = 101) and patients with inflammatory bowel disease (N = 42; Crohn's disease, N = 18 and ulcerative colitis, N = 24). All serum samples were tested by indirect immunofluorescence to the anti-endomysium antibodies (EmA), anti-neutrophil cytoplasmic (ANCA), anti-smooth-muscle (SMA), anti-mitochondrial (AMA), anti-nuclear (ANA), anti-liver-kidney microsomal (LKM), anti-gastric parietal cells (GPCA), and anti-thyroid microsome (TMA). EmA were detected in 100% of celiac patients ingesting gluten and in 16.1% of the first-degree relatives, while ANCA were positive only in patients with ulcerative colitis (45.6%) and Crohn's disease (16.5%). Fourteen CD patients (25%) were positive for at least one of the other autoantibodies, with significant prevalence of TMA, ANA, and GPCA, while the relatives showed 17.8% of positivity, with an increased prevalence of ANA and TMA. These results emphasize the value of screening for different autoantibodies in celiac patients and their relatives and corroborate the need for evaluation and follow-up of these individuals.
