Association of MBL2 Polymorphisms with HAM/TSP in HTLV-1 Infection: A Case-Control Study Approach

Human T-lymphotropic virus type 1 (HTLV-1) infection is usually asymptomatic; however, around 3% of infected individuals develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Host genetic variants of innate immunity may contribute to this clinical outcome.

To investigate the association between MBL2 polymorphisms and HAM/TSP in people living with HTLV-1.

This case-control study included 89 individuals with confirmed HTLV-1 infection who were followed at an outpatient clinic for at least three years. Of these, 64 were asymptomatic and 25 developed HAM/TSP. Polymorphisms in the MBL2 promoter regions -550 (H/L; rs.11003125) and -221 (Y/X; rs.7096206), and in exon 1 (A/O; rs.5030737, rs.1800450, and rs.1800451) were genotyped. Combined haplotypes were classified according to previously described genotype-based functional categories related to high/intermediate or low/deficient MBL production. Serum MBL levels were not directly measured.

The H allele and HH/HL genotypes at -550 were more frequent in asymptomatic individuals than in patients with HAM/TSP. In the combined analysis, low/deficient predicted MBL producers were more frequent in the HAM/TSP group than in the asymptomatic group (48 vs. 23%; OR 3.02, 95% CI 1.01-8.89; p = 0.02).

MBL2 polymorphisms were associated with HAM/TSP status in this cohort. However, these findings should be interpreted cautiously due to the small sample size, the absence of proviral load data for most participants, and the lack of direct serum MBL measurements. Larger independent studies are needed to confirm these associations.