LAMININ-6 AND LAMININ-5 ARE RECOGNIZED BY AUTOANTIBODIES IN A SUBSET OF CICATRICIAL PEMPHIGOID

We characterized basement membrane zone (BMZ) autoantigens targeted by autoantibodies (AAb) from patients with cicatricial pemphigoid, Serum from a patient with severe oral cicatricial pemphigoid contained IgG anti-BMZ AAb, The AAb labeled a lower BMZ component on salt-split skin and localized to the lower lamina lucida/lamina densa by direct and i ndirect, immunoelectron microscopy (IEM) but did not label blood vesse ls, The AAb did not react with EHS laminin-1 and type IV collagen, pep sinized human type IV collagen, recombinant entactin, or NC1 domain of type VII collagen by dot blotting and western blotting. We focused ou r studies on the laminin family, as laminin-5 was identified as an aut oantigen in cicatricial pemphigoid, Culture-conditioned media from nor mal keratinocytes (containing laminin-6 and laminin-5) and JEB keratin ocytes (containing laminin-6 but not laminin-5) were studied by wester n blotting, Under nonreducing conditions, the patient's AAb recognized a 600-kDa protein (laminin-6) intensely and a 400-kDa protein (lamini n-5) weakly in normal keratinocyte medium even though abundant laminin -5 was present, In JEB keratinocyte medium, however, the 600-kDa prote in (laminin-6) alone was recognized by the patient's AAb, The AAb also immunolabeled BMZ of JEB skirt that lacked laminin-5, The AAb from th is patient and two other patients with anti-laminin-5 cicatricial pemp higoid immunoprecipitated both laminin-6 and laminin-5, Taken together , the results of IEM, nonreducing western blotting, immunoprecipitatio n, and JEB skin BMZ immunolabeling indicate that laminin-6, as well as laminin-5, is identified by the AAb from a subset of cicatricial pemp higoid patients. We propose the name ''anti-laminin cicatricial pemphi goid'' for this subset.