Human T cell lymphotropic virus type 1 (HTLV‐1) proviral load of HTLV‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients according to new diagnostic criteria of HAM/TSP

Abstract

A high human T-cell lymphotropic virus type 1 (HTLV-1) proviral load is described in HTLV-1-associated diseases, especially HAM/TSP. However, the cut-off value to define high levels of HTLV-1 proviral load is not well established. 281 HTLV-1-infected patients from the HTLV reference center in Salvador, Brazil, were followed from 2005 to 2008. Patients were classified as asymptomatic, possible-, probable-, and definite-HAM/TSP, in accordance with diagnostic criteria proposed by De Castro-Costa et al. (2006): AIDS Res Hum Retroviruses 22:931-935. HTLV-1 proviral load was determined using real-time PCR. A receiver operator characteristic (ROC) curve was constructed using only asymptomatic individuals and definite-HAM/TSP patients. The ROC curve was used to predict the proviral load level that differentiates these two groups. Out of 281 patients, 189 were asymptomatic and 92 were diagnosed with HAM/TSP (22 possible, 23 probable, 47 definite). The mean HTLV-1 proviral load was higher in possible- (89,104 ± 93,006 copies/106 PBMC), -probable (175,854 ± 128,083 copies/106 PBMC), and definite-HAM/TSP patients (150,667 ± 122,320 copies/106 PBMC),when compared to asymptomatic individuals (27,178 ± 41,155 copies/106 PBMC) (P < 0.0001). A comparison of all HAM/TSP groups showed the highest proviral loads in probable-HAM/TSP patients, yet the differences in mean values were not statistically significant. The ROC curve suggested a value of 49,865 copies/106 PBMC, with 87% sensitivity (95% CI ¼ 74-95) and 81% specificity (95% CI ¼ 75-86), as the best proviral load cut-off point to differentiate definite HAM/TSP patients from asymptomatic individuals. HTLV-1 proviral loads are higher in groups of infected patients with eurological symptoms and may represent a relevant biological marker of disease progression.

Association between HLA alleles and HAM/TSP in individuals infected with HTLV-1

“…However, the relatively small size of our study population might have precluded recognition of any influence of demographics on HTLV-1-associated neurological disease. In contrast, the median HTLV-1 proviral load was significantly greater (*10-fold higher) in HAM/TSP patients than in asymptomatic carriers, as found in other studies [15,17].…”

“…Up to January 2012, a total of 199 individuals with HTLV-1 infection had been reported in Spain. Twenty-five (13 %) had been diagnosed with HAM/TSP using well established criteria [17]. For the purpose of this study, only patients who had frozen peripheral blood mononuclear cells (PBMC) were chosen.…”

“…Clinical outcomes in HTLV-1 carriers most likely depend on an interaction between viral and host genetic factors [7]. In this regard, a high proviral load, specific viral variants and early life infection, such as perinatally from infected mothers, have all been associated with the development of clinical complications in HTLV-1 carriers [13][14][15][16][17].…”

Keratoconjunctivitis sicca of human T cell lymphotropic virus type 1 (HTLV-1) infected individuals is associated with high levels of HTLV-1 proviral load

“…13,14 In HTLV-1 infected individuals, the prevalence of KCS is higher in patients with HAM/TSP diagnosis, when compared to asymptomatic individuals. 15 A higher HTLV-1 proviral load (PVL) has been found in patients with HTLV-associated diseases, especially HAM/TSP, [16][17][18][19] infective dermatitis, 20 and uveitis 21 compared with proviral load from asymptomatic individuals. A recent study found that patients with KCS who were infected by HTLV-1 had a higher PVL than those without KCS.…”

Difficulties in HAM/TSP diagnosis

“…Another alternative consists in quantifying the HTLV-I virus in blood and/or CSF, which presents more elevated levels in patients with HAM/TSP compared to asymptomatic individuals 14 . Grassi et al observed that the ideal viral load in blood, in order to differentiate HAM/ TSP from asymptomatic groups, was 49.865 copies/10 6 PBMC (87% sensitivity and 81% specificity) 15 . In another analysis, the viral load in the CSF contributed to the differential diagnosis of HAM/TSP and multiple sclerosis 7 .…”