The thrombophilic network of autoantibodies in celiac disease

Abstract

BackgroundCeliac disease is a life-long autoimmune condition, affecting genetically susceptible individuals that may present with thromboembolic phenomena. This thrombophilia represents a puzzle with multiple constituents: hyperhomocysteinemia, B12 and\or folate deficiency, methylenetetrahydrofolate reductase mutations, and protein C and S deficiency due to vitamin K deficiency. However, the well known thrombogenic factors, antiphosphatidylserine/prothrombin and antiprothrombin have never been explored in celiac disease.MethodsThe serum autoantibody levels were determined in 248 individuals, classified into three groups. Group 1 comprised 70 children with definitive celiac disease (age: 7.04 ±4.3 years, male to female ratio 1.06) and group 2 comprised 88 normal children (age: 6.7 ±4.17 years, male to female ratio 0.87), representing controls. The pediatric populations were compared to group 3, which included 90 adults who were family members (parents) of group 1 (age: 34.6 ±11.35 years, male to female ratio 1.2). Antibodies were checked by enzyme-linked immunosorbent assay.ResultsMean optical density levels of serum antiphosphatidylserine/prothrombin immunoglobulin G antibodies were 32.4 ±19.4, 3.6 ±2.5 and 16.1 ±15.8 absorbance units in groups 1, 2 and 3 respectively (P <0.0001), with 45.7%, 0% and 7.8% of groups 1, 2 and 3 respectively positive for the antibody (P <0.01). Mean optical density levels of serum antiphosphatidylserine/prothrombin immunoglobulin M antibodies were 14.2 ±8.7, 6.7 ±6.4 and 12.4 ±15.5 absorbance units in groups 1, 2 and 3 respectively (P <0.0001), with 7.1%, 3.4% and 9.9% of groups 1, 2 and 3 positive for the antibody. Mean optical density levels of serum antiprothrombin and antiphospholipid immunoglobulin G antibodies were higher in groups 1 and 3 compared with 2 (P <0.005) and in groups 1 and 2 compared with 3 (P <0.01), respectively. Groups 1, 2 and 3 were positive for antiphospholipid immunoglobulin G antibodies (groups 1 and 2 compared with 3) . Celiac disease sera harbor a higher antiprothrombin immunoglobulin G level compared with controls.ConclusionsIt is suggested that the intestinal injury, endothelial dysfunction, platelet abnormality and enhanced apoptosis recently described in celiac disease are at the origin of the increased exposure of phospholipids or new epitopes representing autoantigens. Those autoantibodies might play a pathogenic role in the thrombophilia associated with celiac disease and represent markers for potential anticoagulant preventive therapy.

Comparison of the Reliability of 17 Celiac Disease Associated Bio-Markers to Reflect Intestinal Damage

“…Hematological and gastrointestinal malignancies, osteoporosis/penia and other extraintestinal manifestations, decreased height, malnutrition and nutritional deficiencies, fertility impairment, stillbirth, dismaturity, hypercoagulability, psychosocial compromise, impairment of quality of life and-if left untreated-increased mortality and additional autoimmune conditions, to name a few [4]. The epidemiology and phenotype of CD are constantly changing, early diagnosis and subsequent adherence to a gluten-free diet is highly recommended.…”

Anti-prothrombin antibodies in type 1 diabetes mellitus

“…aPT: anti-prothrombin; β2GP1: β-2-glycoprotein 1, NA; non-applicable. and significant associations have been reported in several autoimmune diseases [28][29][30][31][32][33][34][35][36]. Yang et al [26] demonstrated the aPT antibodies with prothrombinase activity and suggested that these catalytic aPT antibodies might contribute to thrombosis observed in APS patients.…”

Gluten, Transglutaminase, Celiac Disease and IgA Nephropathy

“…Skin, endocrine, skeletal, hepatic, haematological, thrombophylic, gynaecological, fertility, dental and behavioural abnormalities are often described. Nowadays, we are witnessing an epidemiological shift in the disease phenotype toward a more advanced age, and increased prevalence of latent, hypo symptomatic or asymptomatic behaviour [6,7]. All these changes make the diagnosis of the disease more difficult and the reliance on symptomatology more remote [8].…”