Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor

• Published in: Blood 2008-09, Vol.112 (5), p.2004-2012
• Main Authors: Colombat, Magali, Mal, Hervé, Copie-Bergman, Christiane, Diebold, Jacques, Damotte, Diane, Callard, Patrice, Fournier, Michel, Farcet, Jean-Pierre, Stern, Marc, Delfau-Larue, Marie-Hélène
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Base Sequence; Biological and medical sciences; Cysts - genetics; Cysts - immunology; Cysts - pathology; Cysts - surgery; DNA - genetics; Female; Genes, Immunoglobulin Heavy Chain; Genes, Immunoglobulin Light Chain; Hematologic and hematopoietic diseases; Humans; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - metabolism; Immunoglobulin kappa-Chains - genetics; Immunoglobulin kappa-Chains - metabolism; Immunoglobulin Light Chains - genetics; Immunoglobulin Light Chains - metabolism; Immunoglobulin Variable Region - genetics; Immunoglobulin Variable Region - metabolism; Lung Diseases - genetics; Lung Diseases - immunology; Lung Diseases - pathology; Lung Diseases - surgery; Lung Transplantation; Medical sciences; Molecular Sequence Data; Paraproteinemias - genetics; Paraproteinemias - immunology; Paraproteinemias - pathology; Paraproteinemias - surgery
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-11-123596

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 κ 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.