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OBJECTIVE: To evaluate expression of glucocorticoid-induced tumor necrosis factor receptor (GITR), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and IL-10 in peripheral blood mononuclear cells (PBMCs) of 20 women with unexplained recurrent spontaneous abortion (URSA) compared to 20 normal non-pregnant women (NNP) during luteal phase in the window of implantation. METHODS: Quantitative real-time PCR (qRT-PCR) was performed using the Taqman method for expression of GITR and SYBR Green method for expression of CTLA-4 and IL-10. RESULTS: Expression of CTLA-4 in the NNPs (median; interquartile range; 3; 1.8-10) was significantly higher than the URSAs (0.72; 0.26-3.81, p = 0.015). Expression of GITR in the NNPs (53; 10-139) was significantly higher than the URSAs (6; 3-27, p = 0.005). However, IL-10 expression in the URSAs was significantly higher than the NNPs, did not meet a significant value. A significant correlation was found between CTLA-4 and GITR expression in the study population (p = 0.0001). CONCLUSIONS: Expression of CTLA-4 and GITR were significantly down-regulated in the URSAs compared to NNPs at the window of implantation, which shows the essential role of Treg cells in creating an immunological privileged site for fetus as an allograft at the maternal-fetal interface by high expression levels of CTLA-4 and GITR during a normal pregnancy.
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Aborto Habitual/metabolismo , Biomarcadores/metabolismo , Leucocitos Mononucleares/metabolismo , Linfocitos T Reguladores/metabolismo , Aborto Habitual/sangre , Adulto , Antígeno CTLA-4/sangre , Antígeno CTLA-4/metabolismo , Células Cultivadas , Estudios Transversales , Implantación del Embrión , Femenino , Proteína Relacionada con TNFR Inducida por Glucocorticoide/sangre , Proteína Relacionada con TNFR Inducida por Glucocorticoide/metabolismo , Humanos , Interleucina-10/sangre , Interleucina-10/metabolismo , Fase Luteínica/sangre , Fase Luteínica/inmunología , EmbarazoRESUMEN
BACKGROUND: Prisoners are at high risk of blood borne and sexually transmitted infections due to their high involvement in risky behaviors. In this descriptive/cross-sectional study, the prevalence, sero-prevalence, and risk factors for bloodborne tumor viruses including HTLV-I, HBV, HCV, and KSHV were evaluated among inmates of two central prisons in the northeast of Iran. METHODS: Blood samples of 1114 inmates were analyzed for the presence of anti HTLV-I, KSHV, and HCV antibodies and HBsAg by ELISA. PCR tests were performed to confirm the presence of these viruses in plasma and identify the current infections. RESULTS: The sero-prevalence of HCV, HBV, HTLV-I, and KSHV was 24.5%, 4.2%, 3.4%, and 3.2% and the prevalence of HCV, HBV, HTLV-I, and KSHV was 19.1%, 2.1%, 2%, and 3%, respectively. HCV infection was significantly associated with history of imprisonment, tobacco consumption, alcohol consumption, intravenous drug use, length of imprisonment, and type of crime committed. Thirty one (2.8%) prisoners had HCV-KSHV co-infection, 16 (1.5%) had HCV-HTLV-I co-infection, and 14 (1.3%) had HBV-HCV co-infection. Triple co-infection was observed in seven cases and one case had four infections concomitantly. CONCLUSIONS: This epidemiological study indicated different rates and transmission risks for these viruses. HCV was the most contagious viral infection and HTLV-I was the weakest in the prisoners. Apart from KSHV infection which its prevalence was as twice as in the general population, the prevalence of HBV and HTLV-I in prisoners was nearly in ranges of the general population.
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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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Antiinflamatorios/uso terapéutico , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Productos del Gen tax/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Paraparesia Espástica Tropical , ARN Mensajero/metabolismo , Proteínas de los Retroviridae/metabolismo , Adulto , Antiinflamatorios/farmacología , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Regulación Viral de la Expresión Génica/efectos de los fármacos , Humanos , Interferones/farmacología , Interferones/uso terapéutico , Masculino , Persona de Mediana Edad , Paraparesia Espástica Tropical/complicaciones , Paraparesia Espástica Tropical/tratamiento farmacológico , Paraparesia Espástica Tropical/etiología , Paraparesia Espástica Tropical/patología , Paraparesia Espástica Tropical/virología , Prednisolona/farmacología , Prednisolona/uso terapéutico , Vanadatos/farmacología , Vanadatos/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVE(S): HTLV-I and HIV virus quantification is an important marker for assessment of virus activities. Since there is a direct relationship between the number of virus and disease progression, HTLV-I and HIV co-infection might have an influence on the development of viral associated diseases, thus, viral replication of these viruses and co-infection were evaluated. MATERIALS AND METHODS: In this study, 40 subjects were selected; 14 HIV infected, 20 HTLV-I infected and 6 HTLV-I/HIV co-infected subjects. The amount of viruses was measured using qPCR TaqMan method and CD4 and CD8 lymphocytes were assessed by flow cytometry. RESULTS: The mean viral load of HIV infected subjects and HTLV-I infected individuals were 134626.07±60031.07 copies/ml and 373.6±143.3 copies/10(4) cells, respectively. The mean HIV viral load in co-infected group was 158947±78203.59 copies/ml which is higher than HIV infected group. The mean proviral load of HTLV-I in co-infected group was 222.33±82.56 copies/ml which is lower than HTLV-I infected group (P<0.05). Also, the mean white blood cell count was higher in co-infected group (5666.67±1146.49 cells/µl). However, the differences between these subjects did not reach to a statistical significance within 95% confidence interval level (P =0.1). No significant differences were observed regarding CD4 and CD8 positive lymphocytes between these groups. CONCLUSION: HTLV-I/HIV co-infection might promote HIV replication and could reduce the HTLV-I proviral load, in infected cells. Considering the presence of both viruses in Khorasan provinces, it encourages researchers and health administrators to have a better understanding of co-infection outcome.