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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. 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. Source: BMC Medicine 2013, 11:89. doi:10.1186/1741-7015-11-89
10/05/2009 - Pregnant women with celiac disease suffer early pregnancy loss more often than women without celiac disease. A team of Italian researchers recently set out to look at a possible role of genetic pro-thrombotic variants in early pregnancy loss in women with celiac disease. The research team was made up of C. Ciacci, R. Tortora, O. Scudiero, R. Di Fiore, F. Salvatore, and G. Castaldo. The team looked at 39 women with celiac disease, who had experienced at least two early pregnancy losses within the first 3 months of pregnancy, a control group of 72 celiac women with a history of one or more normal pregnancies with no pregnancy loss. Each of the women were enrolled in the study immediately upon diagnosis for celiac disease, whereupon, the researchers obtained a clinical history obtained from each woman. The researchers then screened leukocyte DNA for factor V Leiden (mutation G1691A), factor V R2 (H1299R), factor II (G20210A), methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), beta-fibrinogen (âˆ’455 G>A), PAI-1 alleles 4G/5G, factor XIII (V34L), and HPA-1 (L33P). Women with pregnancy losses were notably older (p = 0.002) among the celiacs than in controls. Of the gene variants examined, the allelic frequency of 4G variant of PAI-1, and the frequency of mutant genotypes were significantly more frequent in the group of celiac women with early pregnancy loss (p = 0.00003 and 0.028, respectively). Interestingly, the beta-fibrinogen âˆ’455 G>A genotype distribution differs substantially between the two groups, though frequency of the variant allele remains the same. The control group showed more frequent variant genotypes (p = 0.009). Based on these data, the research team believes the 4G variant of the PAI-I gene may predispose some celiac women who carry the gene to early pregnancy loss, though they note that their data should be confirmed on larger populations. Digestive and Liver DiseaseVolume 41, Issue 10, October 2009, Pages 717-720