De rol van complement in subepidermale auto-immuun blaarziekten.

Background: subepidermal autoimmune bullous skin diseases (sAIBD) is a group of diseases characterized by an autoantibody respons to proteins located in the basement membrane zone. Whether or not complement is involved in the pathogenesis of these diseases is controversial. Several hypotheses on the role of complement exist. However, studies testing these hypotheses on the basis of clinical, immunological and histological patient characteristics, are sparce. AIM: In this study we investigate the relationship between the presence of complement and clinical, histological and immunological variables. We expect that the presence of complement in a patient population with sAIBD defines a different population than the sAIBD patients without the presence of complement. Material and methods: Patients diagnosed with sAIBD and positive direct immunofluorescence were selected from our database over the period 2002-2012. They were included in the study and analyzed retrospectively. Clinical, histological and immunological data were collected from various databases and the electronic patient record. Clinical variables were the presence of blisters, itching and erythema. Immunological variables were immune depositions with complement and antibodies. Histological variables were the type of skin biopsy and the type of blister. Univariate and multivariate analysis were used to examine if there was an association between the presence of complement and the above variables. Results: A total of 371 patients were included in this study. Complement was present in the majority (69%) of the sAIBD patients. Most frequently it was seen in pemphigoid gestationis and anti-laminin-332 pemphigoid (100%), followed by bullous pemphigoid (BP) (82%), mucous membrane pemphigoid and lichen planus pemphigoides (67%) and epidermolysis bullosa acquisita (44%). In lineair IgA dermatosis there was no presence of complement. In non-bullous pemphigoid, a subgroup of BP without blisters, complement was less frequently (33%) observed. Complement was found in both lesional, perilesional and (apparently) healthy skin. In BP a (weak) relationship was found between complement and blisters and between complement and BP180 antibodies. There were no associations between complement and the other parameters. Conclusion: In this study we could not demonstrate that the presence of complement defines a different patient population than the patients without complement. This study does not exclude a complement-dependent inflammatory mechanism in certain patient populations with sAIBD. However, complement activation does not necessarily lead to blister formation and disease activity in sAIBD. Therefore it is likely that in addition to complement activation, other non-complement-dependent mechanisms also play a role.