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.