Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor.
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.
Colombat
Magali
M
Assistance Publique des Hôpitaux de Paris (APHP), Hôpital Tenon, Service d'anatomie pathologique, Paris, France.
Mal
Hervé
H
Copie-Bergman
Christiane
C
Diebold
Jacques
J
Damotte
Diane
D
Callard
Patrice
P
Fournier
Michel
M
Farcet
Jean-Pierre
JP
Stern
Marc
M
Delfau-Larue
Marie-Hélène
MH
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
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D004247:DNA