Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP

In order to examine the effect of HTLV-I proviral load on the pathogenesis of HAM/TSP, we measured the HTLV-I proviral load in peripheral blood mononu clear cells (PBMC) from a large number of HAM/TSP patients and asymptomatic HTLV-I carriers. To measure the proviral load, we used an accurate and rep roducible quantitative PCR method using a dual-labeled fluorogenic probe (A BI PRISM 7700 Sequence Detection System). The mean +/- standard error of me an (s.e.m.) HTLV-I proviral copy number per 1 x 10(4) PBMC was 798 +/- 51 ( median 544) in 202 HAM/TSP patients; 120 +/- 17 (median 34) in 200 non HAM- related (general) asymptomatic HTLV-I carriers (RC); and 496 +/- 82 (median 321) in 43 asymptomatic HTLV-I carriers genetically related to HAM/TSP pat ients (FA). The prevalence of HAM/TSP rises exponentially with log (provira l load) once the proviral load exceeds 1% PBMC. The HTLV-I proviral load of female patients with HAM/TSP was significantly higher than that of male pa tients, however there was no significant difference in proviral load betwee n sexes in RC. There was a significant correlation between the proviral loa d and the concentration of neopterin in CSF of HAM/TSP patients. These resu lts indicate that the HTLV-I proviral load in PBMC may be related to the in flammatory pro cess in the spinal cord lesion. The increased proviral load in FA suggests the existence of genetic factors contributing to the replica tion of HTLV-I in vivo.