Autoimmunity to heat shock proteins and vitamin D status in patients with celiac disease without associated dermatitis herpetiformis

Abstract

Inflammation-induced heat shock proteins (HSPs) and hypovitaminosis D have been reported to impact immune responses and to be associated with autoimmune diseases including celiac disease (CD), a gluten-sensitive enteropathy mediated by autoantibodies against tissue transglutaminase (TG2). Recently, we provided evidence for a role of autoantibodies to HSPs in patients with dermatitis herpetiformis (DH), an inflammatory skin disease induced by underlying latent CD. In this study, we aimed at investigating the humoral autoimmune response to HSPs and vitamin D status in CD patients (n=15) presenting without the cutaneous disease manifestation. In comparison with healthy controls (n=15), circulating autoantibodies against HSP40, HSP60, and HSP90 were increased in these patients, and these autoantibodies, including anti-HSP70, correlated with serum anti-TG2 autoantibodies. Deficient and insufficient vitamin D serum levels were found in 8 out of 15 CD patients and 11 out of 15 healthy controls, and the vitamin D status showed no relationship with levels of circulating anti-TG2 or anti-HSP autoantibodies in the patients. Our results preliminarily suggest a pronounced anti-HSP autoimmune response in CD that is linked to pathophysiological processes in the gut independently of both a potential concomitant disease-related extra-intestinal inflammatory manifestation in the skin and the vitamin D status. Future studies on larger groups of patients are needed to confirm the present data and to further clarify whether autoimmunity towards HSPs is primarily related to underlying CD or skin inflammation in DH patients.