title: Mannan-binding lectin and ficolin deposition in skin lesions of pemphigus.
abstract: Pemphigus is characterized by circulating autoantibodies directed against desmossomal antigens that, once bound to target antigens, induce disruption in the cell-cell adhesion of the epidermis and mucosal epithelium, leading to blister formation. Evidence has indicated a role for complement in the physiopathology of pemphigus, with complement deposition in intercellular spaces of skin and mucous membrane lesions. Mannan-binding lectin (MBL) and Ficolin-2 are recognition proteins of innate immunity, which by binding to specific molecular patterns on pathogens surfaces trigger the activation of complement, leading to phagocytosis and lyses of target cells and inflammation. In this study we report for the first time the deposition of MBL and ficolins in pemphigus lesions. Eight biopsies of skin lesions of pemphigus vulgaris were studied for in situ deposition of IgG and the complement components MBL, Ficolin 1, Ficolin-2, C1q, C3 and membrane attack complex C5b-9. All biopsies presented deposition of IgG and C3 in the intercellular spaces (ICS) of epidermis. MBL deposition was found in the ICS and basal membrane zone (BMZ) of all specimens, whereas C5b-9 showed deposition only in the ICS, with irregular distribution. Ficolin-2 were positive in 50% (4/8) of biopsies showing deposition in the BMZ. On the other hand, ficolin-1 and C1q were negative in all specimens. Our study suggest that MBL and to a lesser extend Ficolin-2 may bind to altered intercellular structures in the skin and lead to the activation of complement in situ, contributing to tissue damage in pemphigus.
authors.affiliation: Laboratory of Molecular Immunopathology, Department of Clinical Pathology, Hospital de Clínicas, Federal University of Paraná, Rua Padre Camargo, Curitiba, PR, Brazil. iarareason@hc.ufpr.br
authors.forename: Iara Jose
authors.initials: IJ
authors.lastname: de Messias-Reason
authors.forename: Renato Mitsunori
authors.initials: RM
authors.lastname: Nisihara
authors.forename: Valmir
authors.initials: V
authors.lastname: Mocelin
mesh_terms: D000936:Antigen-Antibody Complex / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D001768:Blister; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000378:metabolism*; D010392:Pemphigus / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000473:pathology; D000097604:Ficolins
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D003165:Complement System Proteins; D007074:Immunoglobulin G; D037102:Lectins; D037601:Mannose-Binding Lectin; D051192:Receptors, Pattern Recognition; D000097604:Ficolins