title: Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor.
abstract: We have recently described a new form of light chain deposition disease (LCDD) presenting as a severe cystic lung disorder requiring lung transplantation. There was no bone marrow plasma cell proliferation. Because of the absence of disease recurrence after bilateral lung transplantation and of serum-free light chain ratio normalization after the procedure, we hypothesized that monoclonal light chain synthesis occurred within the lung. The aim of this study was to look for the monoclonal B-cell component in 3 patients with cystic lung LCDD. Histologic examination of the explanted lungs showed diffuse nonamyloid kappa light chain deposits associated with a mild lymphoid infiltrate composed of aggregates of small CD20(+), CD5(-), CD10(-) B lymphocytes reminiscent of bronchus-associated lymphoid tissue. Using polymerase chain reaction (PCR), we identified a dominant B-cell clone in the lung in the 3 studied patients. The clonal expansion of each patient shared an unmutated antigen receptor variable region sequence characterized by the use of IGHV4-34 and IGKV1 subgroups with heavy and light chain CDR3 sequences of more than 80% amino acid identity, a feature evocative of an antigen-driven process. Combined with clinical and biologic data, our results strongly argue for a new antigen-driven primary pulmonary lymphoproliferative disorder.
authors.affiliation: Assistance Publique des Hôpitaux de Paris (APHP), Hôpital Tenon, Service d'anatomie pathologique, Paris, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Colombat
authors.forename: Hervé
authors.initials: H
authors.lastname: Mal
authors.forename: Christiane
authors.initials: C
authors.lastname: Copie-Bergman
authors.forename: Jacques
authors.initials: J
authors.lastname: Diebold
authors.forename: Diane
authors.initials: D
authors.lastname: Damotte
authors.forename: Patrice
authors.initials: P
authors.lastname: Callard
authors.forename: Michel
authors.initials: M
authors.lastname: Fournier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Farcet
authors.forename: Marc
authors.initials: M
authors.lastname: Stern
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Delfau-Larue
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D001483:Base Sequence; D003560:Cysts / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000601:surgery; D004247:DNA / Q000235:genetics; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain; D050439:Genes, Immunoglobulin Light Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000378:metabolism*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000378:metabolism; D008171:Lung Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000601:surgery; D016040:Lung Transplantation; D008969:Molecular Sequence Data; D010265:Paraproteinemias / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000601:surgery
chemical_list: D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D004247:DNA