A significant association between CXCL10 -1447 A > G and IL18 -607 C > A gene polymorphism with human T-cell lymphotropic virus type 1 associated myelopathy/tropical spastic paraparesis (HAM-TSP), a case-control report from city of Mashhad, Iran.

Human T-cell lymphotropic virus type 1 (HTLV-1) is the first isolated retrovirus from humans, and 2-3% of infected individuals suffer from HTLV-1 associated myelopathy tropical spastic paraparesis (HAM-TSP). Previous studies indicated that the risk of HAM-TSP could be correlated with the individuals' genetic alterations. Mashhad is one of the areas infected with HTLV-1 in Iran. This study designed to examine the association between several important gene polymorphisms and HAM-TSP. Genotypes of 232 samples from controls, HTLV-1 carriers, and HAM-TSP patients were examined for FAS-670 (A > G), CXCL10-1447 (A > G), Foxp3-3279 (C > A), IL-18 -137 (C > G), and IL-18 -607 (C > A) gene polymorphisms by different polymerase chain reaction (PCR) techniques. A non-significant association was observed between FAS-670 A > G, Foxp3-3279 C > A, and IL-18 -137 C > G gene polymorphisms and HAM-TSP. Nevertheless, a significant (P < 0.001) association between CXCL10-1447 A > G and IL-18 -607 C > A gene polymorphisms with HAM-TSP was observed in our study population. As previous studies revealed that the CXCL10 level in the cerebrospinal fluid of HAM-TSP patients was associated with the disease progression, and as we noticed, a direct association was observed between CXCL10-1447 A > G polymorphism and HAM-TSP. These polymorphisms might be recommended as a valuable prediction criterion for the severity of the disease. The contradiction between our findings and other studies regarding IL-18 -607 C > A gene polymorphism might be associated with various factors such as genotypes frequency in diverse races and population heterogeneity in the city of Mashhad.

Acupuncture in the treatment of HTLV-I-associated myelopathy / tropical spastic Paraparesis.

We investigate the possible effects of acupuncture on the improvement of neurological problems in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)disease. Twenty patients with HAM/TSP were studied in this pre and post-test clinical trial. Urinary incontinence, global motor disability, spasticity, and pain severity were evaluated before, one month, and three-month after the intervention. Analyses demonstrated a significant reduction of urinary symptoms one month after acupuncture (P = 0.023). A significant improvement was observed in patients' pain and the spasticity at the upper extremity joints, one and three-month after the intervention (P < 0.05). This study suggests that body acupuncture can be used as a complementary treatment to improve HAM/TSP neurological symptoms.

HTLV-1-infected asymptomatic carriers compared to HAM/TSP patients over-express the apoptosis- and cytotoxicity-related molecules.

HTLV-1 infection causes a chronic progressive debilitating neuroinflammatory disease which is called, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). One of the host defense mechanisms against viral infection is apoptosis which may control HTLV-1 infection. Therefore, we aimed to investigate this process and its interaction with viral factors in HTLV-1-infected asymptomatic carriers (ACs) compared to HAM/TSP patients. Fas, FasL, TRAIL, perforin, granzyme A, granzyme B, and granulysin gene expression and serum levels of Fas, FasL, TRAIL, and granulysin in the peripheral blood of 21 sex- and age-matched healthy controls (HCs), ACs, and HAM/TSP patients were evaluated. Also, the level of granulysin secretion in the cell culture supernatant was measured. Finally, the correlation of the expression of these molecules with HTLV-1 proviral load (PVL), Tax, and HBZ mRNA expression was analyzed. ACs compared to HAM/TSP patients significantly over-expressed the Fas, FasL, TRAIL, perforin, and granzyme B molecules. Fas, FasL, TRAIL, and granulysin serum levels were not different among studied groups; whereas, the secretion of granulysin was significantly decreased in ACs and HAM/TSP patients compared to HCs. Also, HAM/TSP patients expressed higher levels of HTLV-1 PVL, Tax, and HBZ mRNA. In addition, in ACs, inverse correlations between the Fas, FasL, TRAIL, perforin, granzyme B, and granulysin levels with HBZ mRNA expression were seen. ACs compared to HAM/TSP patients over-expressed the apoptosis- and cytotoxicity-related molecules. It could be concluded that successful control of the HTLV-1 infection and suppression of HAM/TSP development stem from the strong apoptosis and cytotoxic activity in the peripheral blood of ACs.

Modulatory effects of curcumin on apoptosis and cytotoxicity-related molecules in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

Apoptosis is a universal cellular defense mechanism against viral infection. Curcumin, an anti-inflammatory phytochemical, induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. Here, we investigated the impact of supplementation with curcumin on the expression of a panel of apoptosis- and cytotoxicity-related genes in patients suffering from HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive demyelinating neuroinflammatory disease caused by HTLV-1 infection. Twenty-one HAM/TSP patients enrolled in this study. Curcumin nanomicelles (80mg/day, orally) were administered once a day for 12 weeks. The mRNA levels of total Fas (tFas), membrane-bound Fas (mFas), Fas-Ligand (FasL), TNF-related apoptosis-inducing ligand (TRAIL), perforin, granzyme A, granzyme B and granulysin were analyzed before and after treatment in peripheral blood lymphocytes. Protein levels of Fas, FasL, TRAIL and granulysin were also measured in serum using ELISA. Curcumin supplementation inhibited FasL mRNA production and up-regulated the expression of pro-apoptotic molecules granzyme A (at the mRNA level) and granulysin (at the protein level), suggesting degranulation of granulysin-bearing cells following curcumin supplementation. Conversely, Curcumin did not affect Fas, TRAIL, perforin, granzyme B at the mRNA level, and anti-apoptotic molecules sFas, sFasL and sTRAIL at the protein level. The present results suggest that curcumin supplementation increases cytotoxicity-related molecules granzyme A and granulysin in patients with HAM/TSP.