RESUMEN

Mannose binding lectin-associated serine protease 2 (MASP2) is the effector part of mannose binding lectin (MBL) that activates the complement system in an antibody-independent manner. We aimed to investigate the role of genetic polymorphisms in the MASP2 gene and susceptibility to HTLV-1 infection. A total of 172 HTLV-1 infected individuals and 170 healthy blood donors were analyzed in this case-control study. Nine single nucleotide polymorphisms (SNPs) encompassing different regions of the MASP2 gene were genotyped with a polymerase chain reaction-sequence-specific primer (PCR-SSP) assay. The relation between the SNPs genotype and the susceptibility to HTLV-1 infection was investigated with a χ2 test considering P < 0.05 as statistically significant. Two of nine tested SNPs were associated with the risk of HTLV-1 infection. The genotype TT at rs17409276 decreased the risk of HTLV-1 (P = 0.005, OR = 0.301, 95% CI = 0.124-0.728). The genotypes CC and CT at rs2273346 were also associated with a higher risk of HTLV-1 acquisition (P = 0.004, OR = 2.225, 95% CI = 1.277-3.877). These findings highlight the importance of MASP2 genetic polymorphisms in the lectin pathway of complement activation and susceptibility to HTLV-1 infection.

Asunto(s)

Infecciones por HTLV-I , Serina Proteasas Asociadas a la Proteína de Unión a la Manosa , Donantes de Sangre , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Infecciones por HTLV-I/genética , Virus Linfotrópico T Tipo 1 Humano , Humanos , Irán , Lectinas/genética , Serina Proteasas Asociadas a la Proteína de Unión a la Manosa/genética , Serina Proteasas Asociadas a la Proteína de Unión a la Manosa/metabolismo , Polimorfismo de Nucleótido Simple

RESUMEN

It is estimated that about 10-20 million peoples are infected with human T-cell leukemia virus type 1 (HTLV-1) around the world and suffered from HTLV-related diseases. The present study was aimed to evaluate the cellular immunity, T-cell activation, humoral immunity, and inflammatory response hallmarks which affect HTLV-1-associated disease progression. A total of 78 participants were included in the study, comprising 39 HTLV-1 asymptomatic careers (ACs) and 39 healthy controls. The HTLV-proviral load (PVL) was determined via real-time PCR technique, and anti-HTLV antibody, sIL2R, sCD30, Neoptrin, hs-CRP, IgE, anti-VCA, anti-EBNA, and anti-EA were assessed by ELISA method. Mean PVL in ACs was 352.7 ± 418.7 copies/104 PBMCs. A significant higher level of sIL-2R was observed in ACs (P < 0.0001). Anti-VCA antibody titer in ACs and healthy controls was 80.72 ± 105.95 and 156.05 ± 130.71, respectively (P = 0.007). Intriguingly, suppression in ACs immune response was not observed. Resultantly, HTLV-1 infection has no effect on the humoral immune response in ACs but greater T-cell activation and function cellular responses were detected. Finally, more studies on various immune markers in adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients are greatly needed to illuminate the association of ACs' immune status with the development of the related diseases.

Asunto(s)

Linfocitos T CD4-Positivos/inmunología , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Inmunidad Celular , Inmunidad Innata , Adulto , Anticuerpos Antivirales/sangre , Enfermedades Asintomáticas , Proteína C-Reactiva/inmunología , Proteína C-Reactiva/metabolismo , Linfocitos T CD4-Positivos/virología , Estudios de Casos y Controles , Femenino , Infecciones por HTLV-I/sangre , Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-I/virología , Humanos , Inmunoglobulina E/sangre , Subunidad alfa del Receptor de Interleucina-2/sangre , Subunidad alfa del Receptor de Interleucina-2/inmunología , Irán , Antígeno Ki-1/sangre , Antígeno Ki-1/inmunología , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Neopterin/sangre , Neopterin/inmunología , Carga Viral

RESUMEN

BACKGROUND: The role of (MBL) gene single nucleotide polymorphisms (SNPs) has been well documented in susceptibility to several infectious diseases. This study aimed to investigate the association between two MBL promoter variants, -550 H/L and -221 X/Y, and susceptibility to HTLV-1 infection. METHODS: A total of 153 subjects infected with HTLV-1 and 169 healthy controls were recruited. SSP-PCR method was applied to genotype -550 H/L and -221 X/Y polymorphisms. Associations between genotypes or alleles and susceptibility to HTLV-1 infection were analyzed by Pearson's Chi-Square. p ≤ .05 was considered statistically significant. RESULTS: Statistical analysis revealed significant differences between the two groups in the -221 position (χ2 = 19.709; p = .000). The MBL YX genotype was significantly associated with increased susceptibility to HTLV-1 (OR = 2.73, %95 CI = 1.74-4.30). Combined genotype of the two loci showed that the HYHX genotype (OR = 2.20, 95% CI = 1.95-2.48) and LYLX (OR = 1.97, 95% CI = 1.13-3.45) were associated with an increased risk of HTLV-1 infection. CONCLUSION: Our results represent the importance of -221 X > Y variants in acquisition of HTLV-1 as this is the case for several other viral and bacterial infections.

Asunto(s)

Predisposición Genética a la Enfermedad , Infecciones por HTLV-I/etiología , Virus Linfotrópico T Tipo 1 Humano , Lectina de Unión a Manosa/genética , Polimorfismo de Nucleótido Simple , Alelos , Sustitución de Aminoácidos , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Genotipo , Infecciones por HTLV-I/diagnóstico , Humanos , Irán/epidemiología , Masculino , Oportunidad Relativa , Regiones Promotoras Genéticas

RESUMEN

AIM: Human T lymphotropic virus type 1 (HTLV-1) infection with high prevalence in the north-east of Iran, particularly in Mashhad, can lead to adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and a variety of autoimmune diseases. The aim of the study was to examine the presence of autoimmune markers in HTLV carries. METHODS: Serum samples were obtained from blood donors in Mashhad, northeastern Iran. One hundred and five HTLV-1 positive (cases) and 104 age- and sex-matched HTLV-1 negative donors (controls) were assessed for presence of serum autoimmune markers by enzyme-linked immunosorbent assay. RESULTS: The mean ages of cases and controls were 40.8 ± 9.4 and 41.5 ± 9.3 years, respectively (P = 0.5). In the case group, 81.9% and in the control group 83.7% were male (P = 0.74). The frequency of positive antinuclear antibodies and anticyclic citrullinated peptide antibodies in the serum of the two groups were not significantly different (P = 0.68 and P = 0.62, respectively). Only one antineutrophil cytoplasmic antibody-positive case (1%) was observed in the group and no anti-phospholipid immunoglobulin G positivity was observed. The frequency of rheumatoid factor (RF) was greater in case group than in the control group, although the difference was not significant (P = 0.08). The amount of RF in all 12 RF positive sera were higher than normal levels (33-37 IU/mL). CONCLUSION: Because we failed to detect any significant relation between serum autoimmune markers and HTLV-1 infection, and because of the relatively low prevalence of autoimmune diseases, it could be concluded that healthy HTLV-1 carriers do not produce rheumatologic-related auto-antibodies more than the healthy population.

Asunto(s)

Autoanticuerpos/sangre , Autoinmunidad , Portador Sano/inmunología , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Adulto , Anticuerpos Antiproteína Citrulinada/sangre , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Antinucleares/sangre , Biomarcadores/sangre , Portador Sano/sangre , Portador Sano/virología , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por HTLV-I/sangre , Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-I/virología , Interacciones Huésped-Patógeno , Humanos , Irán , Masculino , Persona de Mediana Edad , Pruebas Serológicas

RESUMEN

Recruitment of leukocytes by chemokines and chemokine receptors to CNS plays a crucial role in the induction of inflammatory response in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In the present study, chemokine and chemokine receptors involved in trafficking of lymphocytes to the CNS were measured in HAM/TSP patients, HTLV-1 asymptomatic carriers (ACs), and healthy controls. The PVL, CCR6, and CXCR3 mRNA expression, and CXCL9 and CXCL10 protein levels were measured in all subjects. The PVL of HAM/TSP patients was higher than that of ACs (P = 0.02). CCR6 expression was higher in HAM/TSP patients and in ACs compared to the healthy controls (P = 0.005 and P = 0.04, respectively). A significant difference was observed in CCR6 expression when a combination of HAM/TSP patients and ACs were compared to the healthy individuals (P = 0.005). Furthermore, there was a significantly lower CXCR3 expression between HAM/TSP and control groups (P = 0.001), and between the ACs and healthy controls (P = 0.001). However, the increased CXCR3 expression in ACs compared to HAM/TSP patients was not significant. Furthermore, the CXCL10 protein levels in HAM/TSP patients was higher than in controls (P = 0.012), and CXCL9 protein levels was also higher in the HAM/TSP and ACs groups than in the controls (P = 0.001 and P = 0.004, respectively). In conclusion, it seems that decreased expression of CXCR3 and higher expression of CCR6 were associated with HTLV-1 infection, what indicate that these alterations may favor virus dissemination but not disease manifestation.

Asunto(s)

Portador Sano/patología , Infecciones por HTLV-I/patología , Receptores CCR6/análisis , Receptores CXCR3/análisis , Adulto , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proteoma/análisis , ARN Mensajero/análisis , Adulto Joven