Do Autoantibodies Play a Pathogenic Role in Celiac-associated Thrombophilia?

Celiac.com 06/03/2013 - Thrombophilias are defined as a group of inherited or acquired disorders that increase a person’s risk of developing thrombosis (abnormal “blood clotting”) in the veins or arteries.

People with celiac disease may present with thromboembolic features that have multiple contributing factors, such as hyperhomocysteinemia, B12 andor folate deficiency, methylenetetrahydrofolate reductase mutations, and protein C and S deficiency due to vitamin K deficiency.

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However, there has been no research into how the well known thrombogenic factors, antiphosphatidylserine/prothrombin and antiprothrombin relate to celiac disease.

A team of researchers recently studied the thrombophilic network of autoantibodies in celiac disease.

The research team included Aaron Lerner1, Nancy Agmon-Levin, Yinon Shapira, Boris Gilburd, Sandra Reuter, Idit Lavi and Yehuda Shoenfeld.

They are variously affiliated with Epidemiology and Community Medicine, and the Pediatric Gastroenterology and Nutrition Unit in the Carmel Medical Center of the B. Rappaport School of Medicine at the Technion-Israel institute of Technology in Haifa, Israel, with the Zabludowicz Center for Autoimmune Diseases at Sheba Medical Center in Tel-Ashomer, Israel, and with Aira e.v./Aesku.Kipp Institute in Wendelsheim, Germany.

For their study, the team assessed blood autoantibody levels in 248 people, and then classified them into one of three groups.

Group 1 included 70 children with confirmed celiac disease. They averaged 7.04 years of age (±4.3 years), with a male to female ratio of 1.06 to 1.

Group 2 was a healthy control group that included 88 children, averaging 6.7 years of age (±4.17 years), with a male to female ratio 0.87 to 1.

The team then compared the pediatric population 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). The check antibodies using enzyme-linked immunosorbent assay.

Results showed average optical density levels of serum antiphosphatidylserine/prothrombin immunoglobulin G antibodies of 32.4 ±19.4, 3.6 ±2.5 and 16.1 ±15.8 absorbance units in groups 1, 2 and 3 respectively (P less than 0.0001), with 45.7%, 0% and 7.8% of groups 1, 2 and 3 respectively positive for the antibody (P less than 0.01).

Average 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 less than 0.0001), with 7.1%, 3.4% and 9.9% of groups 1, 2 and 3 positive for the antibody.

Average optical density levels of serum antiprothrombin and antiphospholipid immunoglobulin G antibodies were higher in groups 1 and 3 compared with 2 (P less than 0.005) and in groups 1 and 2 compared with 3 (P less than 0.01), respectively.

Groups 1, 2 and 3 tested positive for antiphospholipid immunoglobulin G antibodies (groups 1 and 2 compared with 3) . Celiac disease blood samples contain a higher antiprothrombin immunoglobulin G level compared with controls.

These results suggest that increased exposure of phospholipids or new epitopes representing autoantigens have their origins in the intestinal injury, endothelial dysfunction, platelet abnormality and enhanced apoptosis recently described in celiac disease.

Those autoantibodies might play a pathogenic role in celiac-associated thrombophilia, and may also make good targets for possible preventive anticoagulant therapy.

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