Population differences in immune marker profiles associated with human T‐lymphotropic virus type I infection in Japan and Jamaica

Abstract

The natural history of human T‐lymphotropic virus type I (HTLV‐I) has been shown to differ markedly by geographic area. The differences include contrasting patterns of risk of adult T‐cell lymphoma (ATL) and HTLV‐I‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may be due in part to differences in host immune response to infection. To characterize variations in host immunity across populations, we compared serologic immune marker patterns in HTLV‐I‐endemic populations in Japan and Jamaica. We matched 204 participants with archived blood from the Miyazaki Cohort Study (Japan) and the Food Handlers Study (Jamaica)—i.e., 51 HTLV‐I‐positive (“carriers”) and 51 HTLV‐I‐negative individuals (“noncarriers”) from each population—by age, sex and blood collection year. We compared plasma concentrations of markers of T‐cell‐mediated (antigen‐specific) and nonspecific immunity using regression models and correlation coefficients. Compared to Jamaican HTLV‐I noncarriers, Japanese noncarriers had higher covariate‐adjusted mean levels of T‐cell activation markers, including antibody to Epstein‐Barr virus nuclear antigen‐1 (reciprocal titer 27 vs. 71, respectively, p = 0.005), soluble interleukin‐2 receptor‐α (477 vs. 623 pg/mL, p = 0.0008) and soluble CD30 (34 vs. 46 U/mL, p = 0.0001) and lower levels of C‐reactive protein (1.1 vs. 0.43 μg/mL, p = 0.0004). HTLV‐I infection was associated with activated T‐cell immunity in Jamaicans but with diminished T‐cell immunity in Japanese persons. The observed population differences in background and HTLV‐I‐related host immunity correspond closely to the divergent natural histories of infection observed among HTLV‐I carriers in Japan and Jamaica and corroborate a role for host immune status in the contrasting patterns of ATL and HAM/TSP risk. © 2008 Wiley‐Liss, Inc.

Pre-diagnosis plasma immune markers and risk of non-Hodgkin lymphoma in two prospective cohort studies

“… 14 Of note, comparatively high sIL-2Rα levels at diagnosis were also associated with poor prognosis in patients with NHL. 39 – 41 Biologically, sIL-2Rα and sCD30 are highly correlated (r=0.58 in this study), and both can indicate B-and T-cell activation; 42 in the present analysis, both markers remained independently associated with a significant increased risk of all NHL and all B-NHL after mutual adjustment. In contrast, only sIL-2Rα was significantly associated with an increased risk of T-NHL in the multi-marker models, although small sample size (n=30 cases) limited statistical power to detect significant independent associations for more strongly correlated biomarkers.…”

In vivo expression of the HBZ gene of HTLV-1 correlates with proviral load, inflammatory markers and disease severity in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP)

“…As we have already confirmed and reported the same levels of Tax protein expression in HTLV-1-infected PBMCs between HAM/TSP patients and HCs in the same cohort [ 50 ], the observed discrepancy may be due to the differences of a number of host genetic and virologic factors in HTLV-1 infected individuals, including differences in HLA haplotypes [ 51 - 53 ], differences in the amount of soluble suppressive factors and CD8+ T-cell responses, and differences in HTLV-1 tax genomic sequences [ 54 ]. As a recent report indicated that HTLV-I infection was associated with activated T-cell immunity in Jamaicans but with diminished T-cell immunity in Japanese persons [ 55 ], the interaction between different genes and/or environmental factors is also likely to contribute to the observed differences between the two populations. Namely, genetic resistance to infectious diseases that is formed by complex host genetic effects might be complicated further by pathogen diversity and environmental factors.…”

Susceptibility of human T‐cell leukemia virus type I‐infected cells to humanized anti‐CD30 monoclonal antibodies in vitro and in vivo

“…( 19 ) Tax induces the constitutive activation of transcription factor activator protein‐1, ( 56,57 ) which might result in an autocrine loop of CD30‐mediated activation of NF‐κB in HTLV‐I‐infected cells, as previously observed in HL and ALCL cells. ( 58 ) In addition to the membrane‐associated form of CD30, sCD30 in the sera of patients with ATL ( 20,59–61 ) would be a useful marker to evaluate the clinical progression of ATL as well as HL or ALCL. ( 59,62–65 ) The sCD30 binds to CD30L with high affinity and blocks transmembrane signaling by CD30, ( 66 ) suggesting that the elevated level of sCD30 in sera might also decrease antitumor effects of the CD30 mAbs by blocking the antiproliferative signaling through cell cycle arrest and apoptosis.…”