title: Integrated expression of glomerular extracellular matrix proteins and beta 1 integrins in monoclonal light chain-related renal diseases.
abstract: Light-chain deposition disease (LCDD) and amyloid light-chain amyloidosis (AL-Am) represent the two classical diseases associated with glomerular alterations in monoclonal light chain-related renal diseases. LCDD is characterized by deposition of extracellular matrix proteins in the mesangium, thus creating the morphologic appearance recognized as nodular glomerulosclerosis. In AL-Am, the mesangial matrix is replaced by polymerized light chains in the form of amyloid fibrils. Integrins are responsible for cell-to-cell and cell-to-matrix communication and, therefore, are expected to play a key role in the alterations encountered in these two diseases. The present article addresses the expression of selected extracellular matrix proteins (collagen IV, laminin, fibronectin, and tenascin) and their respective receptor beta 1 integrins (alpha 2, alpha 3, alpha 5, and alpha 9) in glomeruli with LCDD and AL-Am by immunohistochemical methods. The corresponding integrin (alpha 9 beta 1) co-localized with tenascin in the center of the mesangial nodules in LCDD. In AL-Am, tenascin is found primarily at the periphery of replaced mesangial areas and in the remaining mesangium not replaced by the amyloid. Tenascin co-localized with alpha 9 beta 1 integrin in mesangial areas in the earlier phases of the process. Fibronectin, laminin, and collagen IV, although increased in absolute amounts, are pushed toward the periphery of mesangial areas, in which correlated expression of their corresponding beta 1 integrins (alpha 2, alpha 3, and alpha 5, respectively) is documented in both LCDD and AL-Am. Deposition of tenascin might be at least partially responsible for the perpetuation and irreversibility of the glomerular lesion in LCDD.
authors.affiliation: Department of Pathology, Overton Brooks Veterans Administration Medical Center, Shreveport, Louisiana, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Turbat-Herrera
authors.forename: J
authors.initials: J
authors.lastname: Isaac
authors.forename: P W
authors.initials: PW
authors.lastname: Sanders
authors.forename: L D
authors.initials: LD
authors.lastname: Truong
authors.forename: G A
authors.initials: GA
authors.lastname: Herrera
mesh_terms: D000418:Albumins / Q000378:metabolism; D000686:Amyloidosis / Q000276:immunology / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007105:Immune Complex Diseases / Q000276:immunology / Q000378:metabolism*; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism*; D007150:Immunohistochemistry; D039001:Integrin alpha Chains; D039201:Integrin alpha3beta1; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008854:Microscopy, Electron; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism
chemical_list: D000418:Albumins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007136:Immunoglobulins; D039001:Integrin alpha Chains; D039201:Integrin alpha3beta1; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin; D019063:Tenascin; C084613:integrin alpha9; D005340:Fibrinogen; D003094:Collagen