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IgG anti-laminin-332 autoantibodies are present in a subset of patients with mucous membrane, but not bullous, pemphigoid
Journal article   Open access

IgG anti-laminin-332 autoantibodies are present in a subset of patients with mucous membrane, but not bullous, pemphigoid

Zelmira LAZAROVA, Valerie K SALATO, Christoph M LANSCHUETZER, Marleen JANSON, Janet A FAIRLEY and Kim B YANCEY
Journal of the American Academy of Dermatology, Vol.58(6), pp.951-958
2008
DOI: 10.1016/j.jaad.2008.02.035
PMCID: PMC2517626
PMID: 18396347
url
http://doi.org/10.1016/j.jaad.2008.02.035View
Open Access

Abstract

Background: Antiepiligrin cicatricial pemphigoid is a mucosal-predominant subepidermal blistering disease associated with an increased relative risk of cancer. In contrast to prior reports showing that anti-laminin (L)-332 autoantibodies are a reliable marker for patients with antiepiligrin cicatricial pemphigoid, a recent report suggested that as many as 40% of patients with bullous pemphigoid (BP) have IgG reactive with this laminin isoform. Objective: We sought to determine whether patients with BP possess circulating IgG anti-L-332 autoantibodies. Methods: Sera from 100 adults with BP were analyzed by indirect immunofluorescence testing of intact skin, immunoblot studies of human keratinocyte (HK) extracts, and a new L-332 enzyme-linked immunosorbent assay. Sera showing reactivity suggestive of anti-L-332 autoantibodies in these assays were further analyzed in immunoblot studies of HK extracellular matrix and immunoprecipitation studies of biosynthetically radiolabeled HK extracts. Results: IgG from all patients with BP bound intact epidermal basement membrane by indirect immunofluorescence microscopy and immunoblotted bullous pemphigoid antigen-1, -2, or both in HK extracts. None of these sera immunoblotted L-332 in HK extracts, although 13 did score above the cut point of a new IgG(4) L-332 enzyme-linked immunosorbent assay (sensitivity = 0.91, specificity = 0.98, Youden index = 0.89). Further analysis of sera from these 13 patients found: (1) all had IgG that bound the epidermal side of 1 mol/L NaCl split skin by indirect immunofluorescence microscopy; (2) none immunoblotted L-332 purified from HK extracellular matrix; and (3) none immunoprecipitated L-332 from biosynthetically radiolabeled HK extracts. Limitations: The basis of false-positive enzyme-linked immunosorbent assay determinations for anti-L-332 IgG among patients with BP is unknown. Conclusion: Anti-L-332 autoantibodies remain a reliable marker for patients with antiepiligrin cicatricial pemphigoid.
 Dermatology Biological and medical sciences Medical sciences Bullous diseases of the skin

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