The thrombophilic network of autoantibodies in celiac disease

BMC Medicine

Yehuda Shoenfeld¹  Idit Lavi⁴  Sandra Reuter³  Boris Gilburd¹  Yinon Shapira¹  Nancy Agmon-Levin¹  Aaron Lerner² 

[1]The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Ashomer, 52621, Israel

[2]Pediatric Gastroenterology and Nutrition Unit, Carmel Medical Center, B. Rappaport School of Medicine, Technion-Israel institute of Technology, Michal St. No 7, Haifa, 34362, Israel

[3]Aira e.v./Aesku.Kipp Institute, Mikroforum Ring 3, Wendelsheim, 55234, Germany

[4]Carmel Medical Center, Epidemiology and Community Medicine, Michal St. No 7, Haifa, 34362, Israel

关键词: Prothrombin;    Phospholipid;    Hypercoagulability;    Celiac disease;    Autoantibodies;    Antiphosphatidylserine/prothrombin;   

Others  :  857118
DOI  :  10.1186/1741-7015-11-89

 received in 2012-10-16, accepted in 2013-01-11,  发布年份 2013

【 摘 要 】

Background

Celiac 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.

Methods

The 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.

Results

Mean 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.

Conclusions

It 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.

【 授权许可】

   
2013 Lerner et al.; licensee BioMed Central Ltd.

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