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-alpha (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 microg/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.

Figure 1

Median titers, inter-quartile ranges, and maximum observed titers of (A) anti-EBNA1, (B) anti-EBNA2, and (C) anti-VCA and prevalence of (D) anti-EA seropositivity and (E) low EBNA1:EBNA2 ratio, in HTLV-I-uninfected (□) and HTLV-I-infected (■) participants from Japan and Jamaica.

Figure 2

Median levels, inter-quartile ranges, and maximum observed plasma levels of (A) C-reactive protein, (B) soluble IL-2 receptor, (C) soluble CD30, (D) neopterin, and (E) total IgE, in HTLV-I-uninfected (□) and HTLV-I-infected (■) participants from Japan and Jamaica.