HLA DR-DQ combination associated with the increased risk of developing human HCV positive non-Hodgkin's lymphoma is related to the type II mixed cryoglobulinemia

V. De Re, L. Caggiari, G. Monti, M. Libra, M. Spina, R. Dolcetti, M. De Zorzi, V. Racanelli, M. Crovatto, G. Toffoli

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)127-135
Number of pages9
JournalTissue Antigens
Issue number2
Publication statusPublished - Feb 2010



  • Autoimmunity
  • B-cells
  • Hepatitis C virus
  • Lymphoma
  • Molecules major histocompatibility complex

ASJC Scopus subject areas

  • Genetics
  • Immunology
  • Immunology and Allergy

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