The impact of interferon-alpha treatment on clinical and immunovirological aspects of HTLV-1-associated myelopathy in northeast of Iran

Rafatpanah, Houshang; Rezaee, Seyed Abdolrahim; Etemadi, M M; Hosseini, Reza Farid; Khorram, Bita; Afsahr, Leila; Taylor, Graham P.; Mokhber, Naghmeh; Mahmoudi, Mahmoud; Abbaszadegan, Mohammad Reza; Foroghipor, Mohsen; Hashemi, Peyman; Amiri, Amin; Tehrani, Mohsen; Azarpazhooh, Amir; Azarpazhooh, Mahmoud Reza

doi:10.1016/j.jneuroim.2012.05.004

Cited by 37 publications

(28 citation statements)

References 29 publications

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“…In other studies, at least 4 weeks of treatment with IFN-α showed a relative improvement (33-88 %) of clinical symptoms, particularly motor disability, but no significant improvement of urinary disturbance was observed [38,39]. Our previous study of IFN-α-treated patients with HAM/TSP showed a significant but temporary effect in motor and bladder functions [25]. PVL significantly decreased in responders and nonresponders, 1 and 6 months after the treatment.…”

Section: Discussionmentioning

confidence: 65%

“…Recently, IFN-α was used in patients with HAM/TSP, and clinical and immunological improvements were assessed. Six-month treatment had a temporary positive effect on motor disability, spasticity, and urinary disturbances [25]. Moreover, a remarkable decrease in HTLV-1 viral load, antibody level, and lymphocyte and monocyte counts was observed.…”

Section: Introductionmentioning

confidence: 90%

“…Then, HTLV-1 and albumin DNA concentrations from two 5-point standard curves were calculated. The normalized HTLV-I PVL values were measured as the ratio of (HTLV-1 DNA copies number/albumin DNA copies number/2)×10 4 and expressed as the number of HTLV-1 proviruses per 10 4 PBMC [25].…”

Section: Measurement Of Htlv-1 Pvlmentioning

confidence: 99%

“…Specific HTLV-1 antibody titration was carried out before and after the treatment, as previously described [25]. Sera were collected and frozen at -40°C.…”

Section: Htlv-1 Antibody Titrationmentioning

confidence: 99%

“…It should be considered that, owing to the slow progression of the disease, the chance of improvement is increased during the first [10,23]. Although glucocorticoid therapy has been relatively effective in improving motor function, patients who fail to respond to corticosteroids or those who cannot tolerate it because of adverse effects, plasma exchange or IFN-α could be used [10,[24][25][26][27]. Recently, IFN-α was used in patients with HAM/TSP, and clinical and immunological improvements were assessed.…”

Section: Introductionmentioning

confidence: 99%

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Triple Therapy with Prednisolone, Pegylated Interferon and Sodium Valproate Improves Clinical Outcome and Reduces Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Load, Tax and HBZ mRNA Expression in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

et al. 2015

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Considering that there is no effective treatment for human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis, this study aimed to assess the impact of triple combination therapy-interferon-α, valproic acid, and prednisolone-on clinical outcomes, main HTLV-1 viral factors, and host anti-HTLV-1 antibody response. HTLV-1 proviral load (PVL), and HBZ and Tax mRNA expression levels were measured in peripheral blood mononuclear cells of 13 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis before and after treatment with 180 μg pegylated interferon once a week, 10-20 mg/kg/day sodium valproate, and 5 mg/day prednisolone for 25 weeks using a TaqMan real-time polymerase chain reaction assay. Furthermore, anti-HTLV-1 titer, Osame Motor Disability Score, Ashworth spasticity scale, and urinary symptoms (through standard questionnaire and clinical monitoring) were assessed in patients before and after the treatment. HTLV-1 PVL and HBZ expression significantly decreased after the treatment [PVL from 1443±282 to 660±137 copies/10 4 peripheral blood mononuclear cells (p= 0.01); and HBZ from 8.0±1.5 to 3.0±0.66 (p<0.01)]. Tax mRNA expression decreased after the treatment from 2.26± 0.45 to 1.44±0.64, but this reduction was not statistically significant (p=0.10). Furthermore, anti-HTLV-1 titer reduced dramatically after the treatment, from 3123±395 to 815±239 (p<0.01). Clinical signs and symptoms, according to Osame Motor Disability Score and Ashworth score, improved significantly (both p<0.01). Urinary symptoms and sensory disturbances with lower back pain were reduced, though not to a statistically significant degree. Although signs and symptoms of spasticity were improved, frequent urination and urinary incontinence were not significantly affected by the triple therapy. The results provide new insight into the complicated conditions underlying HTLV-1-associated diseases.

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Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 90%

Section: Measurement Of Htlv-1 Pvlmentioning

confidence: 99%

“…Specific HTLV-1 antibody titration was carried out before and after the treatment, as previously described [25]. Sera were collected and frozen at -40°C.…”

Section: Htlv-1 Antibody Titrationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Triple Therapy with Prednisolone, Pegylated Interferon and Sodium Valproate Improves Clinical Outcome and Reduces Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Load, Tax and HBZ mRNA Expression in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

et al. 2015

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Curcumin increased the expression of c‐FLIP in HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients

Poursina

Mohammadi

Yazdi

et al. 2019

J of Cellular Biochemistry

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Human T‐cell lymphotropic virus type 1 (HTLV‐1)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) disease is a chronic neuroinflammatory disease, which is associated with HTLV‐1 infection. There is no effective and satisfactory treatment of HAM/TSP. It has been shown that curcumin exhibits modulatory effects on apoptosis and cytotoxicity‐related molecules in HAM/TSP patients. In the present study, we examined the effect of curcumin on the gene expression of caspase‐8, caspase‐10, and anti‐apoptotic protein c‐FLIP, in HAM/TSP patients. Furthermore, we compared the expression of these molecules between HAM/TSP and asymptomatic carriers. Real‐time PCR was performed to examine the mRNA expression of caspase‐8, caspase‐10, and c‐FLIP in studied groups. The mRNA expression of caspase‐8 and caspase‐10 was similar before and after curcumin treatment in HAM/TSP patients (P > 0.05). The mRNA expression of c‐FLIPL and c‐FLIPs was higher after curcumin treatment compared with before treatment and significant differences were observed between the two groups (P = 0.004 and P = 0.044, respectively). The mRNA expression levels of caspase‐8, caspase‐10, c‐FLIPL, and c‐FLIPs were not statistically significant between HAM/TSP patients and asymptomatic carriers (P < 0.05). In conclusion, our results showed that curcumin increased the expression of c‐FLIP in HAM/TSP patients which might suggest that, this molecule is involved in the apoptosis of HTLV‐1‐infected cells. Further studies with large sample size could be useful to clarify the role of this supplement in HAM/TSP patients.

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Prevalence and phylogenetic analysis of HTLV‐1 in a segregated population in Iran

Rafatpanah

Torkamani

Valizadeh

et al. 2016

Journal of Medical Virology

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Human T-lymphotropic virus type 1 (HTLV-1) infection is an important health issue that affects a variety of endemic areas. The Khorasan province, mainly its capital Mashhad in northeastern Iran, was reported to be as one of these endemic regions. Torbat-e Heydarieh, a large city Southwest border to Mashhad with a segregated population was investigated for the prevalence and associated risk factors of HTLV-1 infection in 400 randomly selected individuals. Blood samples were tested for the presence of HTLV-1 antibodies via the ELISA method and then were confirmed by an Immunoblot test. For the presence of HTLV-1 in lymphocytes of infected subjects, PCR was performed on LTR and TAX regions. DNA sequencing of LTR fragment was also carried out to determine the phylogenetic of HTLV-1, using the Maximum likelihood method. HTLV-1 sero-reactivity (sero-prevalence) among the study population was 2% (8/400), of which 1.25% had HTLV-1 provirus in lymphocytes (actual prevalence). HTLV-1 infection was significantly associated with the age, marital status, and history of blood transfusion (P < 0.05). However, there were no statistical differences between HTLV-1 infection, and gender, surgery, and hospitalization. In regression analysis, age showed the most significant correlation with the infection (P = 0.006, OR = 4.33). Based on our phylogenetic study, the HTLV-1 prevalent sequence type of Torbat-e Heydarieh belongs to the cosmopolitan subtype A. HTLV-1 prevalence in Torbat-e Heydarieh (1.25%) is low comparing to those of both Mashhad (2-3%) and Neishabour (3.5-5%) in the province of Khorasan. Thus, traveling mobility and population mixing such as marriage, bureaucratic affairs, occupation, and economic activities could be the usual routs of HTLV-1 new wave of spreading in this segregated city.

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The impact of interferon-alpha treatment on clinical and immunovirological aspects of HTLV-1-associated myelopathy in northeast of Iran

Cited by 37 publications

References 29 publications

Triple Therapy with Prednisolone, Pegylated Interferon and Sodium Valproate Improves Clinical Outcome and Reduces Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Load, Tax and HBZ mRNA Expression in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

Triple Therapy with Prednisolone, Pegylated Interferon and Sodium Valproate Improves Clinical Outcome and Reduces Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Load, Tax and HBZ mRNA Expression in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

Curcumin increased the expression of c‐FLIP in HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients

Prevalence and phylogenetic analysis of HTLV‐1 in a segregated population in Iran

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