The thrombophilic network of autoantibodies in celiac disease

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

Serum markers of infections in patients with primary biliary cirrhosis: evidence of infection burden.

International audienceBACKGROUND: Currently not much is known regarding the environmental factors involved in primary biliary cirrhosis (PBC). It is even more unclear which factors may determine the subgroup (i.e., AMA status) of patients with PBC. We thus tested AMA+and AMA- PBC patients' sera for antibodies (Abs) against multiple infectious agents. METHODS: Sera from 69 patients with PBC (49 AMA+and 20 AMA-) and 100 matched controls were screened for IgG-Abs against Toxoplasma gondii, Helicobacter pylori, Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B, and hepatitis C utilizing the BioPlex 2200 and ELISA kits (Bio-Rad Laboratories, USA). RESULTS: The prevalence of four anti-infectious agents Abs was significantly elevated among PBC patients when compared with controls, namely anti-T. gondii (ATxA; 71% vs. 40%, p<0.0001), EBV early antigen (EA; 44% vs. 12%, p<0.0001), H. pylori (54% vs. 31%, p<0.01), and CMV (90% vs. 75%, p<0.05) Abs, respectively. The co-occurrence of these four anti-infectious agents Abs was highly common in PBC, whereas this infection burden was rare in healthy subjects (20% vs. 3% respectively, p<0.0001). Furthermore, specific infections interactions possibly increasing PBC risk were noted as well. Seropositivity of ATxA was inversely associated with cirrhosis among PBC patients (p<0.05). Finally, no differences were observed between AMA- sera and their AMA+counterparts with regard to seroprevalence of any of the investigated infectious agents. CONCLUSIONS: We note the association of ATxA and PBC, with the possibility of a milder disease manifestation. We also suggest that multiple exposures to infectious agents may contribute to PBC risk

Elastic Deformation of Optical Coherence Tomography Images of Diabetic Macular Edema for Deep-Learning Models Training: How Far to Go?

&#x2013; Objective: To explore the clinical validity of elastic deformation of optical coherence tomography (OCT) images for data augmentation in the development of deep-learning model for detection of diabetic macular edema (DME). Methods: Prospective evaluation of OCT images of DME (n &#x003D; 320) subject to elastic transformation, with the deformation intensity represented by ( $\sigma$ ). Three sets of images, each comprising 100 pairs of scans (100 original &#x0026; 100 modified), were grouped according to the range of ( $\sigma$ ), including low-, medium- and high-degree of augmentation; ( $\sigma$ &#x003D; 1-6), ( $\sigma$ &#x003D; 7-12), and ( $\sigma$ &#x003D; 13-18), respectively. Three retina specialists evaluated all datasets in a blinded manner and designated each image as &#x2019;original&#x2018; versus &#x2019;modified&#x2018;. The rate of assignment of &#x2019;original&#x2018; value to modified images (false-negative) was determined for each grader in each dataset. Results: The false-negative rates ranged between 71-77&#x0025; for the low-, 63-76&#x0025; for the medium-, and 50-75&#x0025; for the high-augmentation categories. The corresponding rates of correct identification of original images ranged between 75-85&#x0025; ( \text{p}> 0.05) in the low-, 73-85&#x0025; ( \text{p}> 0.05 for graders 1 &#x0026; 2, p &#x003D; 0.01 for grader 3) in the medium-, and 81-91&#x0025; ( \text{p} < 0.005 ) in the high-augmentation categories. In the subcategory ( $\sigma$ &#x003D; 7-9) the false-negative rates were 93-83&#x0025;, whereas the rates of correctly identifying original images ranged between 89-99&#x0025; ( \text{p}> 0.05 for all graders). Conclusions: Deformation of low-medium intensity ( $\sigma$ &#x003D; 1-9) may be applied without compromising OCT image representativeness in DME. Clinical and Translational Impact Statement&#x2014;Elastic deformation may efficiently augment the size, robustness, and diversity of training datasets without altering their clinical value, enhancing the development of high-accuracy algorithms for automated interpretation of OCT images

Helicobacter pylori serology in autoimmune diseases - Fact or fiction?

Background: The pathogenesis of autoimmunity is presumed to be a complex process including genetic predisposition, hormonal balance and environmental factors such as infectious agents . Helicobacter pylori , a common bacterial infectious agent has been associated with a variety of autoimmune disorders. However, this bacteria is also thought to play a protective role in the development of multiple sclerosis (MS), systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD). We tested various links between anti- H. pylori (anti-HP) antibodies and a wide profile of autoimmune diseases and autoantibodies. Methods: A total of 1290 patients diagnosed with 14 different autoimmune diseases from two geographical areas (Europe and Latin America) and two groups of healthy matching controls (n = 385) were screened for the presence of H. pylori IgG antibodies by ' pylori detect ' kit. In parallel, a large profile belonging to three groups of autoantibodies was tested in all sera (anti-nuclear antibodies, autoantibodies associated with thrombophilia and gastrointestinal diseases). Results: Our data demonstrate associations between anti-HP antibodies and anti-phospholipid syndrome, giant cell arteritis, systemic sclerosis and primary biliary cirrhosis. Our data also support a previously known negative association between the prevalence of anti-HP antibodies and IBD. Additionally, links were made between seropositivity to H. pylori and the presence of anti-nuclear antibodies, dsDNA, anti-Ro and some thrombophiliaassociated antibodies, as well as negative associations with gastrointestinal-associated antibodies. Conclusions: Whether these links are epiphenomenal or H. pylori does play a causative role in the autoimmune diseases remains uncertain. The negative associations could possibly support the notion that in susceptible individuals infections may protect from the development of autoimmune diseases

Low levels of vitamin-D are associated with neuropathy and lymphoma among patients with Sjögren's syndrome.

International audienceBACKGROUND/PURPOSE: Primary Sjögren's syndrome (SS) is a chronic autoimmune disease primarily involving the exocrine glands. The clinical picture of SS ranges from exocrinopathy to systemic disease affecting the lung, kidney, liver, skin, musculockeletal and nervous systems. The morbidity of SS is mainly determined by extraglandular disease and increased prevalence of lymphoma. Environmental and hormonal factors, such as vitamin-D may play a role in the pathogenic process and disease expression. Thus, we aimed to evaluate levels of vitamin-D and their association with manifestations of SS. METHODS: Vitamin-D levels were determined in 176 primary SS patients and 163 matched healthy volunteers utilizing the LIAISON chemiluminescent immunoassays (DiaSorin-Italy). A correlation between vitamin-D levels and clinical and serological manifestations of SS was performed. RESULTS: Mean vitamin-D levels were comparable between SS patients and control 21.2 ± 9.4 ng/ml and 22.4 ± 10 ng/ml, respectively. Peripheral neuropathy was diagnosed in 23% of SS patients and associated with lower vitamin-D levels (18.6 ± 5.5 ng/ml vs. 22.6±8 ng/ml (p = 0.04)). Lymphoma was diagnosed in 4.3% of SS patients, who had lower levels of vitamin-D (13.2 ± 6.25 ng/ml), compared to SS patients without lymphoma (22 ± 8 ng/ml), (p = 0.03). Other clinical and serological manifestations did not correlate with vitamin-D status. CONCLUSIONS: In this study, low levels of vitamin-D correlated with the presence of peripheral neuropathy and lymphoma among SS patients. The link between vitamin-D and neuropathy or lymphoma was reported in other conditions, and may support a role for vitamin-D in the pathogenesis of these processes. Plausible beneficial effect for vitamin-D supplementation may thus be suggested

Low levels of vitamin-D are associated with neuropathy and lymphoma among patients with Sjogren&apos;s syndrome

Background/purpose: Primary Sjogren’s syndrome (SS) is a chronic autoimmune disease primarily involving the exocrine glands. The clinical picture of SS ranges from exocrinopathy to systemic disease affecting the lung, kidney, liver, skin, musculockeletal and nervous systems. The morbidity of SS is mainly determined by extraglandular disease and increased prevalence of lymphoma. Environmental and hormonal factors, such as vitamin-D may play a role in the pathogenic process and disease expression. Thus, we aimed to evaluate levels of vitamin-D and their association with manifestations of SS. Methods: Vitamin-D levels were determined in 176 primary SS patients and 163 matched healthy volunteers utilizing the LIAISON chemiluminescent immunoassays (DiaSorin-Italy). A correlation between vitamin-D levels and clinical and serological manifestations of SS was performed. Results: Mean vitamin-D levels were comparable between SS patients and control 21.2 +/- 9.4 ng/ml and 22.4 +/- 10 ng/ml, respectively. Peripheral neuropathy was diagnosed in 23% of SS patients and associated with lower vitamin-D levels (18.6 +/- 5.5 ng/ml vs. 22.6 +/- 8 ng/ml (p = 0.04)). Lymphoma was diagnosed in 4.3% of SS patients, who had lower levels of vitamin-D (13.2 +/- 6.25 ng/ml), compared to SS patients without lymphoma (22 +/- 8 ng/ml), (p = 0.03). Other clinical and serological manifestations did not correlate with vitamin-D status. Conclusions: In this study, low levels of vitamin-D correlated with the presence of peripheral neuropathy and lymphoma among SS patients. The link between vitamin-D and neuropathy or lymphoma was reported in other conditions, and may support a role for vitamin-D in the pathogenesis of these processes. Plausible beneficial effect for vitamin-D supplementation may thus be suggested. (C) 2012 Elsevier Ltd. All rights reserved