Human leukocyte antigen (HLA) A1-B8-DR3 (8.1) haplotype, tumor necrosis factor (TNF) G-308A, and risk of non-Hodgkin lymphoma

AbstractHuman T-cell lymphotropic virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia and HTLV-1–associated myelopathy/tropical spastic paraparesis. HTLV-1–associated myelopathy/tropical spastic paraparesis is a chronic inflammatory disease characterized by loss of motor movement in response to spinal marrow cell destruction by T lymphocytes. To perform their cellular function, T cells need to be activated by antigen-presenting cells, such as dendritic cells (DCs). The aim of this work was to analyze DC differentiation and activation from monocytes of HTLV-1–infected individuals. We demonstrated that monocytes from HTLV-1–infected patients who had been stimulated to differentiate had an impaired loss of CD14 expression, expressed low levels of CD1a, and maintained secretion of tumor necrosis factor-α compared with monocytes from noninfected donors. We further evaluated DC activation by tumor necrosis factor-α. We observed that in response to activation, DCs that were derived from noninfected donors had an increase in the percentage of CD83+, CD86+, and human leukocyte antigen-DR+ cells, whereas in DCs derived from HTLV-1–infected patients, the percentage of CD83+, CD86+, and human leukocyte antigen-DR+ cells remained similar to that of nonactivated cells. Moreover, these cells had an impaired capacity to stimulate allogeneic T lymphocytes. We demonstrated that DC maturation was altered in HTLV-1–infected patients, which could contribute to the development of HTLV-1–associated diseases.

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Human leukocyte antigens class II and tumor necrosis factor genetic polymorphisms are independent predictors of non-Hodgkin lymphoma outcome

Blood ◽

10.1182/blood-2002-02-0654 ◽

2002 ◽

Vol 100 (8) ◽

pp. 3037-3040 ◽

Cited By ~ 59

Author(s):

Przemyslaw Juszczynski ◽

Ewa Kalinka ◽

Jacques Bienvenu ◽

Grzegorz Woszczek ◽

Maciej Borowiec ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Hodgkin Lymphoma ◽

Tumor Necrosis ◽

International Prognostic Index ◽

Prognostic Index ◽

Human Leukocyte ◽

Non Hodgkin Lymphoma ◽

Leukocyte Antigens ◽

Lymphotoxin Alpha ◽

Necrosis Factor

Tumor necrosis factor (TNF) production and non-Hodgkin lymphoma (NHL) outcome was found to be related to the TNF−308polymorphism. To explore whether this could be linked to neighboring polymorphisms, we genotyped the TNF−376,−308,−238,−163, lymphotoxin alpha (LTα)+252, and HLA DRB1 alleles in 204 patients with NHL and 120 controls. TNF−308A was the only allele associated with higher TNF and its p55 and p75 receptors' levels (P = .009, P = .03, andP = .007) and lower complete remission rates (P = .006). Freedom from progression (FFP) and overall survival (OS) were shorter in patients with TNF−308A(P = .009 and P = .02), null HLA DRB1*02 allele (P = .007 and P = .14), or both genetic markers (P = .004 and P = .005). Multivariate analysis incorporating International Prognostic Index (IPI) identified TNF−308A (P < .0001, relative risk [RR] = 1.63; P < .0001, RR = 1.51) and null HLA DRB1*02 alleles (P = .015, RR = 1.18;P < .0001, RR = 1.25) as independent factors for FFP and OS. These results indicate the existence of at least 2 inherited factors involved in NHL outcome.

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