Neurologic, clinical, and immunologic features in a cohort of HTLV-1 carriers with high proviral loads

Abstract

A high proviral load (PVL) is recognized as a risk factor for human T cell leukemia virus-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but there is a lack of prospective studies evaluating whether or not HTLV-1 carriers with high PVL are at risk of developing HAM/TSP or other HTLV-1-related diseases. Here, we compare the incidence of clinical manifestations and the cytokine levels in 30 HTLV-1 carriers with high (> 50,000 copies/10 6 PBMC) and an equal number of subjects with low proviral load. Participants were followed for 3 to 16 years (median of 11 years). The PVL, IFN-γ, TNF, and IL-10 levels were quantified at entry and at the end of the follow-up. Among the self-reported symptoms in the initial evaluation, only the presence of paresthesia on the hands was more frequent in the group with high PVL (p < 0.04). The production of IFN-γ was higher in the group with high PVL group (median of 1308 versus 686 pg/ml, p < 0.011) when compared with the control group in the first assessment. There was no difference in the occurrence of urinary symptoms or erectile dysfunction, periodontal disease, Sicca syndrome, and neurologic signs between the two groups during the follow-up. The observation that none of the HTLV-1 carriers with high PVL and with exaggerated inflammatory response progressed to HAM/TSP indicates that other factors in addition to the PVL and an exaggerated immune response are involved in the pathogenesis of HAM/TSP.

Systemic cytokines and GlycA discriminate disease status and predict corticosteroid response in HTLV-1-associated neuroinflammation

“…In addition to IL-17A, we found proviral load is an independent biomarker of untreated disease in HAM/ TSP patients, consenting with the literature [4][5][6][7]. However, proviral load did not predict incident HAM/TSP cases in three out of four published Brazilian cohort studies [49][50][51][52]. Of those, only Tanajura et al demonstrated proviral load as a significant predictor of neurological symptoms, but not definite HAM/TSP, during clinical follow-up [50].…”

Systemic cytokines and GlycA discriminate disease status and predict corticosteroid response in HTLV-1-associated neuroinflammation

“…In addition to IL-17A, we found proviral load is an independent biomarker of untreated disease in HAM/TSP patients, consenting with the literature [4][5][6][7]. However, proviral load did not predict incident HAM/TSP cases in three out of four published Brazilian cohort studies [42][43][44][45]. Of those, only Tanajura et al demonstrated proviral load as a signi cant predictor of neurological symptoms, but not de nite HAM/TSP, during clinical follow-up [43].…”

Case Report: Relevance of an Accurate Diagnosis and Monitoring of Infective Dermatitis Associated With Human T-Lymphotropic Virus Type 1 in Childhood

“…This factor represents a great risk for both diseases, IDH and ATLL. High PVL values have been associated with an increased risk of progression to HAM/TSP (19)(20)(21). However, in children with IDH, it has been documented that high PVL is not indicative of progression to HAM/TSP and that PVL values do not decrease after IDH remission.…”