title: Bucillamine induces membranous glomerulonephritis.
abstract: A variety of renal histopathologic lesions, such as amyloidosis, mesangial proliferative glomerulonephritis, and membranous glomerulonephritis (MGN), are associated with rheumatoid arthritis (RA). Bucillamine (BCL), a disease-modifying antirheumatic drug, has a chemical structure and side-effect profile similar to that of d-penicillamine, which can induce MGN in RA. There are a few reports of MGN occurring in association with BCL treatment. However, lacking detailed analyses of immunoglobulin deposition in glomerular lesions, these studies did not elucidate the pathogenesis of BCL-induced MGN. We evaluated seven biopsy specimens from six patients with RA who had undergone BCL treatment with a mean BCL dose of 72.5 g before the appearance of proteinuria. Light microscopic evaluation showed mild to moderate mesangial proliferation. Two biopsy specimens showed spikes along glomerular capillary walls. Granular deposition of immunoglobulin G (IgG) along glomerular capillary walls was seen in all cases, and five specimens showed deposition of IgG2 and/or IgG3 components, in addition to IgG4. Furthermore, subepithelial dense deposits were distributed segmentally in four biopsy specimens on electron microscopy. IgG4, reported to be the predominant IgG subclass deposited, is distributed diffusely in idiopathic MGN. Thus, there were obvious differences between BCL-induced and idiopathic MGN in regard to both IgG subclasses deposited and deposition pattern within the glomerulus. Because IgG3 has the strongest affinity for C1q, these findings suggest that BCL-induced MGN activates the classical pathway more efficiently than idiopathic MGN and that the pathogenesis is different between these two diseases.
authors.affiliation: Department of Pathology, Yokohama City University School of Medicine, Kanagawa, Japan. nag_k@med.yokohama-cu.ac.jp
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nagahama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsushita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hara
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ubara
authors.forename: Shigeko
authors.initials: S
authors.lastname: Hara
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000150:complications*; D003545:Cysteine / Q000009:adverse effects* / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000139:chemically induced* / Q000150:complications / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000139:chemically induced
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003545:Cysteine; C026535:bucillamine