Refining the risk of HTLV-1-associated myelopathy in people living with HTLV-1: identification of a HAM-like phenotype in a proportion of asymptomatic carriers

Abstract

Up to 3.8% of human T-lymphotropic virus type-1 (HTLV-1)-infected asymptomatic carriers (AC) eventually develop HTLV-1-associated myelopathy (HAM). HAM occurs in patients with high (> 1%) HTLV proviral load (PVL). However, this cut-off includes more than 50% of ACs and therefore the risk needs to be refined. As HAM is additionally characterised by an inflammatory response to HTLV-1, markers of T cell activation (TCA), β2-microglobulin (β2M) and neuronal damage were accessed for the identification of ACs at high risk of HAM. Retrospective analysis of cross-sectional and longitudinal routine clinical data examining differences in TCA (CD4/CD25, CD4/HLA-DR, CD8/CD25 & CD8/HLA-DR), β2M and neurofilament light (NfL) in plasma in ACs with high or low PVL and patients with HAM. Comparison between 74 low PVL ACs, 84 high PVL ACs and 58 patients with HAM revealed a significant, stepwise, increase in TCA and β2M. Construction of receiver operating characteristic (ROC) curves for each of these blood tests generated a profile that correctly identifies 88% of patients with HAM along with 6% of ACs. The 10 ACs with this ‘HAM-like’ profile had increased levels of NfL in plasma and two developed myelopathy during follow-up, compared to none of the 148 without this viral-immune-phenotype. A viral-immuno-phenotype resembling that seen in patients with HAM identifies asymptomatic carriers who are at increased risk of developing HAM and have markers of subclinical neuronal damage.

Human T-cell lymphotropic virus screening in France: Missed opportunities? A retrospective multicenter study of serological testing in hospital laboratories

“…Studies are also required on HTLV-1 transmission and HIV pre-exposure prophylaxis. Longitudinal clinical/biological follow-up of people living with HTLV-1 is now required based on recent studies that have shown the possibility of identifying people at risk of HAM/TSP [ 29 ] or patients at a pre-ATLL stage [ 30 ].…”

Patient research priority setting partnership in human T‐cell lymphotropic virus type I

“…Previous studies showed no association between common HAM/TSP symptoms and proviral load, 33–35 and questions remain about the diagnostic accuracy of most biomarkers 12 . A more recent study combining proviral load with markers of inflammation may offer a more refined risk assessment for HAM in asymptomatic carriers 36 . Biomarker tests usually involve invasive procedures.…”

“… 12 A more recent study combining proviral load with markers of inflammation may offer a more refined risk assessment for HAM in asymptomatic carriers. 36 Biomarker tests usually involve invasive procedures. The 10m walk test is a noninvasive measure and has the potential to be used as an outcome measure in clinical trials with people with HTLV‐1, 37 but changes in score are difficult to interpret and demonstrate considerable variability within individuals.…”

Mcl-1 Protein and Viral Infections: A Narrative Review

“…HTLV-1 infects CD4+ and CD8+ T cells, B cells, monocytes, and dendritic cells (DCs). Most of the infected individuals remain asymptomatic for life; however, 2-5% of infected people develop adult T-cell leukemia/lymphoma (ATLL) [65,66], HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) [67,68], or HTLV-1 uveitis (HU) [69].…”