Journal
TISSUE ANTIGENS
Volume 75, Issue 2, Pages 127-135Publisher
WILEY
DOI: 10.1111/j.1399-0039.2009.01414.x
Keywords
autoimmunity; B-cells; hepatitis C virus; lymphoma; molecules major histocompatibility complex
Categories
Funding
- European Community [LSHC-CT-2006-037874]
- Direzione Centrale del Lavoro
- Formazione
- Universita e Ricerca Della Regione Autonoma Friuli Venezia Giulia Codice Progetto [200502027001]
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
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This investigation was focused on the contribution of individual human leukocyte antigen (HLA)-DR and -DQ alleles to the human hepatitis C virus (HCV)+ non-Hodgkin's lymphoma (NHL), with and without mixed cryoglobulinemia (MC), to study whether individual HLA class II alleles are expressed preferentially or equally in human HCV-specific NHL. For this purpose, peripheral blood mononuclear cells were obtained from two groups of patients with HCV+ NHL and with or without MC (70 and 71 cases, respectively), and from 4575 blood donors. Eighty-three subjects with HCV infection only, and 118 patients with MC, only without lymphoma, were added as additional control groups. Individual HLA-DR and -DQ alleles were determined using high-resolution sequence-based typing and then data were collected by considering the HLA-DRB1 and DQB1 supertypes on the basis of common structural and functional features, proposed by in silico Bioinformatic studies. From the data, it is evidenced that the DR5-DQ3 HLA combination was strongly associated with the HCV + MC + NHL group of patients compared with bone marrow donor population (P < 0.001, RR = 2.498), while the contribution of DR1-DQ1 was higher in HCV + NHL without MC (P < 0.001, RR = 2.519). Thus, cryoglobulinemia clinical manifestation was found to be correlated with the preferential use of HLA DR-DQ combination in HCV-associated NHL. These data provide new insight into HCV-associated lymphoproliferative pathogenesis.
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