Patients with bullous pemphigoid and linear IgA disease show a dual IgA and IgG autoimmune response to BP180

Bullous pemphigoid (BP) and Linear IgA disease (LAD) are autoimmune subepid ermal blistering skin diseases associated with autoantibodies against the t ransmembrane hemidesmosomal protein BP180/type XVII collagen. It has been d emonstrated previously that BP is characterized predominantly by IgG autoan tibodies, while autoantibodies in LAD mainly belong to the IgA isotype. The aim of the present study was to investigate the hypothesis that there is a significant overlap in the autoantibody isotype profiles associated with t hese two diseases. Several new recombinant forms of bP180 were generated in the baculovirus expression system, including the full-length protein. IgG autoantibodies to BP 180 were detectable in 39 of 40 (98%) of BP sera; inte restingly, 88% of BP sera also contained IgA anti-BP180 autoantibodies. Sim ilarly, anti-BP180 reactivity in LAD sera (n = 22) was also attributed to b oth an IgA (68%) and an IgG (76%) autoantibody response. IgA and IgG autoan tibodies to the intracellular portion of BP180 were found in 14% and 28% of BP sera, respectively, and in 8% of LAD sera (same percentage for both iso types). Our findings clearly demonstrate that both BF and LAD patients have a dual IgA and IgG autoimmune response to BP180 which is directed not only to the ectodomain, but also to the intracellular portion of this protein. (C) 2000 Academic Press.