Clinical and immunological findings in 104 cases of paraneoplastic pemphigus.

BACKGROUND: Although there are many reports of sporadic patients with paraneoplastic pemphigus (PNP), only a few systematic studies on large cohorts of patients with PNP have been reported. OBJECTIVES: To analyse the clinical and immunological findings in a large cohort of patients with PNP. METHODS: This retrospective study consisted of 104 patients with PNP. Clinical and histopathological manifestations, associated neoplasms, complicating diseases, prognosis and results of immunofluorescence, immunoblotting and enzyme-linked immunosorbent assays (ELISAs) were analysed. RESULTS: The clinical and histopathological findings in this study were generally similar to those in previous reports. The most common associated neoplasms included malignant lymphomas, malignant solid tumours and Castleman disease, in that order, while 12 patients had no detectable tumours. Novel ELISAs for desmocollins (Dscs) showed that 19 (18·6%), 42 (41·2%) and 62 (60·8%) of 102 patients with PNP showed antibodies to Dsc1, Dsc2 and Dsc3, respectively. Thirty-two (60%) of 53 patients had antibodies to alpha-2-macroglobulin-like protein 1 (A2ML1). We found statistically significant correlations between positive desmoglein 3 reactivity and genital lesions, and between positive desmoglein 3 reactivity and bronchiolitis obliterans. CONCLUSIONS: We consider that antibodies to Dscs and A2ML1 are useful for the diagnosis of PNP.

Anti-desmocollin autoantibodies in nonclassical pemphigus.

BACKGROUND: Despite the established pathogenic role of anti-desmoglein (Dsg) antibodies in classical pemphigus, the significance of autoantibodies to another desmosomal cadherin, desmocollin (Dsc) is at present unknown. No consistent immunoassay for immunoglobulin (Ig) G autoantibodies to Dscs has been developed. OBJECTIVES: The aim of this study was to develop reliable assays to detect anti-Dsc autoantibodies. METHODS: We expressed soluble recombinant proteins (RPs) of human Dsc1-3 in mammalian cells and examined sera of various types of pemphigus, including 79 paraneoplastic pemphigus (PNP) sera, by novel enzyme-linked immunosorbent assays (ELISAs) using the RPs. We also performed ELISAs of Dsc baculoproteins and used the complementary DNA (cDNA) transfection method, and compared the results with those of mammalian ELISAs. RESULTS: Through mammalian ELISAs, IgG autoantibodies to Dsc1, Dsc2 and Dsc3 were detected in 16.5%, 36.7% and 59.5% of PNP sera, respectively, and considerable numbers of pemphigus herpetiformis (PH) and pemphigus vegetans (PVeg) sera reacted strongly with Dsc1 and Dsc3. Mammalian ELISAs were highly specific and more sensitive than baculoprotein ELISAs or the cDNA transfection method. Several Dsc-positive sera, particularly PH sera, showed no reactivity with Dsgs. The reactivity of PNP serum and PVeg serum with Dscs was not abolished by pre-absorption with Dsg RPs. CONCLUSIONS: The results of these novel ELISAs indicated that IgG anti-Dsc autoantibodies were frequently detected and potentially pathogenic in nonclassical pemphigus.