Basement membrane antibodies in sera of haematopoietic cell recipients are associated with graft-versus-host disease

• Published in: Journal of the European Academy of Dermatology and Venereology 2010-05, Vol.24 (5), p.587-594
• Main Authors: Hofmann, SC, Kopp, G, Gall, C, Bruckner-Tuderman, L, Bertz, H
• Format: Article
• Language: English
• Subjects: antibodies; Autoantibodies - blood; Basement Membrane - immunology; bullous pemphigoid; Case-Control Studies; cutaneous basement membrane; Enzyme-Linked Immunosorbent Assay; epidermolysis bullosa acquisita; Female; Graft vs Host Disease - immunology; graft-versus-host disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Prospective Studies
• ISSN: 0926-9959; 1468-3083
• DOI: 10.1111/j.1468-3083.2009.03480.x

Background  Graft‐versus‐host disease (GvHD) occurs frequently after haematopoietic cell transplantation (HCT). Mucocutaneous lesions of GvHD may mimic bullous autoimmune dermatoses, and 10 cases of concurrent GvHD and a bullous autoimmune disease have been reported in the literature. Objective  To determine the frequency of circulating antibodies to the cutaneous basement membrane zone (BMZ) in HCT patients with GvHD in comparison with HCT patients without GvHD, psoriasis patients and healthy controls. Subjects and methods  We examined 42 patients with chronic GvHD, 18 HCT patients without GvHD, 11 psoriasis patients and 40 healthy controls, prospectively. Sera were tested by indirect immunofluorescence (IIF) on salt‐split skin, NC16a‐ELISA and immunoblot using keratinocyte extracts. Univariate statistical analyses and logistic regression were performed to assess possible correlations of graft and patient characteristics with the presence of BMZ antibodies. Results  Circulating basement membrane zone (BMZ) antibodies were detected in 10/42 (24%) GvHD sera by immunoblot, but not in any of the HCT sera from patients without GvHD (0/18; 0%). The antibodies targeted collagen VII, BP230, collagen XVII/BP180 or p200/laminin γ1. Clinically manifest bullous autoimmune dermatoses (bullous pemphigoid or epidermolysis bullosa acquisita) were found in two GvHD patients. 1/11 (9%) psoriasis sera and 1/40 (2.4%) healthy control sera reacted with collagen XVII or BP230, respectively. Conclusions  Circulating BMZ antibodies are significantly associated with chronic GvHD in contrast to uncomplicated HCT. Recurrent mucocutaneous lesions in chronic inflammatory skin disorders may liberate antigens, which may lead to production of BMZ antibodies, particularly in the context of GvHD‐mediated reduced self‐tolerance.