- 171: Haematologica. 2008 Jun 12
Molecular analysis of immunoglobulin variable genes in human immunodeficiency virus-related non-Hodgkin's lymphoma reveals implications for disease pathogenesis and histogenesis.
Capello D, Martini M, Gloghini A, Cerri M, Rasi S, Deambrogi C, Rossi D, Spina M, Tirelli U, Larocca LM, Carbone A, Gaidano G.
Department of Clinical and Experimental Medicine & IRCAD, “Amedeo Avogadro” University of Eastern Piedmont, Novara.
Background Human immunodeficiency virus (HIV)-related non-Hodgkin's lymphomas (HIV-NHL) are heterogeneous and associated with distinct molecular pathways. Analysis of immunoglobulin variable genes (IGV) may provide insights into the pathogenesis and histogenesis of HIV-NHL. DESIGN AND METHODS: IGV rearrangements were amplified from genomic DNA by polymerase chain reaction and directly sequenced in 87 cases of HIV-NHL (17 Burkitt/Burkitt-like lymphomas, 38 diffuse large B-cell lymphomas, and 32 primary central nervous system lymphomas). RESULTS: A skewed IGHV repertoire in specific HIV-NHL clinico-pathological categories was observed. Systemic HIV-diffuse large B-cell lymphomas displayed underrepresentation of the IGHV3 family (11/38, 28.9%; p=0.0047) and, in particular, of the IGHV3-23 gene (0/38; p<0.001). These same cases were also characterized by significant overrepresentation of the IGHV4 family (18/38; 47.4%; p=0.0044) and, in particular, of the IGHV4-34 gene (10/38; 26.3%; p=0.003). HIV-primary central nervous system lymphomas displayed a preferential usage of IGLV6-57, with stereotyped B-cell receptor in two cases. Somatic hypermutation of IGHV genes was detected in 81/87 (93.1%) HIV-NHL. Unmutated cases were restricted to six HIV-primary central nervous system lymphomas with immunoblastic plasmacytoid morphology. A mutational profile suggesting a tendency to maintain antigen binding and antigen selection was observed in more than 50% of the cases of IGV mutated HIV-NHL. Conclusions Our data show evidence of a skewed IGHV repertoire in specific HIV-NHL categories and suggest B-cell receptor restriction in some HIV-primary central nervous system lymphomas. The heterogeneous representation of IGHV genes in HIV-NHL may be related to specific pathways of antigen stimulation, or to differences in host's immune dysregulation and lymphoma histogenesis.