Tissue transglutaminase ELISA positivity in autoimmune disease independent of gluten-sensitive disease

Background Our aim was to understand why some sera from patients with a broad spectrum of autoimmune diseases or non-autoimmune diseases involving enhanced apoptosis, cell lysis and/or putative secondary autoimmune processes show reactions in the tissue transglutaminase (TGc) ELISA used for diagnosis of gluten-sensitive disease. Methods Sera were compared from groups of patients with autoimmune diseases, diseases involving organ specific enhanced cell death, celiac disease or dermatitis herpetiformis, diseases of non-autoimmune origin, and a group without known disease. IgA antibodies against TGc were detected using human antigen (produced recombinantly in bacterial or human cells) in different systems (non-commercial ELISA with buffers of differing NaCl concentrations, and anti-TGc sandwich ELISA). Anti-gliadin and anti-endomysium antibodies were also determined. Results Many sera from patients with autoimmune disorders gave a positive signal in the human TGc ELISAs. The signal appeared related to minor impurities in the recombinant human TGc used and to raised serum IgA antibody levels rather than to the occurrence of TGc specific antibodies in these patients. Conclusions No association of anti-TGc Abs and autoimmune conditions independent of gluten-sensitive disease could be shown. Care should be taken to exclude copurification of chaperones, like heat shock protein 70, where preparing antigens for TGc ELISAs. Keywords: Tissue transglutaminase; Celiac disease; Gluten-sensitive disease; Autoimmunity; ELISA