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Molecular analysis of immunoglobulin variable genes in human immunodeficiency virus-related non-Hodgkin’s lymphoma reveals implications for disease pathogenesis and histogenesis

¹ Division of Hematology, Department of Clinical and Experimental Medicine & IRCAD, "Amedeo Avogadro" University of Eastern Piedmont, Novara
² Institute of Pathology, Catholic University of the Sacred Heart, Rome
³ Department of Pathology, Istituto Nazionale Tumori, Milan
⁴ Division of Medical Oncology A, Centro di Riferimento Oncologico, Istituto Nazionale Tumori, IRCCS, Aviano, Italy

Correspondence: Daniela Capello, Ph.D., Division of Hematology, Department of Clinical and Experimental Medicine & BRMA, "Amedeo Avogadro" University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy. E-mail:capello{at}med.unipmn.it

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.

Key words: HIV, lymphoma, immunoglobulin genes, pathogenesis, histogenesis.

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Human immunodeficiency virus-related non-Hodgkin’s lymphoma

Josep-Maria Ribera, José-Tomás Navarro
Haematologica 2008 93: 1129-1132. [Full Text] [PDF]

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				J.-M. Ribera and J.-T. Navarro Human immunodeficiency virus-related non-Hodgkin's lymphoma Haematologica, August 1, 2008; 93(8): 1129 - 1132. [Full Text] [PDF]