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.
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<or= 0.001, RR = 2.498), while the contribution of DR1-DQ1 was higher in HCV (+) NHL without MC (P<or= 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.
De Re
V
V
Centro di Riferimento Oncologico, IRCCS, National Cancer Institute, Aviano, Italy. vdere@cro.it
Caggiari
L
L
Monti
G
G
Libra
M
M
Spina
M
M
Dolcetti
R
R
De Zorzi
M
M
Racanelli
V
V
Crovatto
M
M
Toffoli
G
G
D000483:Alleles; D003449:Cryoglobulinemia / Q000209:etiology / Q000235:genetics* / Q000821:virology*; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D016174:Hepacivirus / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000235:genetics*; D012306:Risk
D006683:HLA-DQ Antigens; C051569:HLA-DQ3 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II