RESUMEN
Leishmaniasis is a parasitic infectious disease with global repercussions. American cutaneous leishmaniasis (ACL) is endemic in southern Brazil and its pathogenesis varies according to parasite species, immune response, and host genetics. In terms of immunogenetics, many host genes, including HLA (human leukocyte antigen), could be involved in susceptibility to and protection against ACL. Accordingly, the aim of this study was to investigate the association between HLA class I genes (HLA-A, -B, and -C) and ACL in an endemic region of southern Brazil. The allele frequencies of 186 patients diagnosed with ACL and 278 healthy individuals were compared. HLA class I (HLA-A, -B, and -C) typing was carried out by PCR-SSO using Luminex technology. The results revealed an association between the HLA-C*04 allele and the patient study group, in which it appeared more frequently than in the control group [21.5 vs 13.49% (P = 0.0016 and Pc = 0.0258; OR = 1.7560; 95%CI = 1.2227-2.5240)], thereby suggesting an increased susceptibility to ACL. Additional allelic groups such as HLA-A*02, HLA-B*35, HLA-B*45, HLA-C*01, and HLA-C*15 were also implicated; however, further investigation is necessary to confirm their association with ACL. Therefore, the results obtained in this study demonstrate the involvement of HLA class I genes in the susceptibility or resistance to ACL, with significant association between HLA-C*04 and ACL susceptibility.
Asunto(s)
Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Antígenos HLA-C/genética , Leishmaniasis Cutánea/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Femenino , Frecuencia de los Genes , Genotipo , Antígenos HLA/genética , Antígenos HLA-B/genética , Humanos , Leishmaniasis Cutánea/patología , Masculino , Persona de Mediana EdadRESUMEN
This study evaluated the association of tumor necrosis factor beta (TNF-ß) NcoI polymorphism with the presence of multiple sclerosis (MS), disability, and HLA-DRB1 alleles in 208 Brazilian MS patients. As controls, 147 healthy individuals were included. The disability was evaluated at baseline and 5-year follow-up using the Expanded Disability Status Scale (EDSS). The TNF-ß genotypes were determined using PCR and restriction fragment length polymorphism and serum TNF-α level was determined using enzyme-linked immunosorbent assay. Among the MS patients, 166 (79.8 %) were white, 39 (18.7 %) were brown, and three (1.4 %) were Asian descents (those were excluded from the further analysis). Among the 205 MS patients, 149 (72.6 %) presented remitting-relapsing MS. The baseline and 5-year follow-up EDSS ranged from 0.0 to 3.0 and from 1.0 to 5.7, respectively. The TNFB2/B2 genotype was associated with the presence of MS among the white patients (p = 0.0443). Brown patients presented higher disability (p = 0.0234) and higher TNF-α levels (p = 0.0463) than white patients. White and brown patients carrying TNFB2/B2 genotype exhibited higher TNF-α levels (p = 0.0354 and p = 0.0309, respectively) than those with other geotypes. Association between TNF-ß NcoI genotypes and HLA-DRB1 alleles was not observed among the MS patients (p > 0.05). Taken together, TNFB2 allele was associated with the presence of MS independently of HLA-DRB1 in white patients and the TNFB2/B2 genotype was associated with increased TNF-α levels in white and brown patients, which could be an important genetic factor candidate for the susceptibility and pathogenesis of MS.
Asunto(s)
Cadenas HLA-DRB1/genética , Linfotoxina-alfa/genética , Esclerosis Múltiple/genética , Polimorfismo de Longitud del Fragmento de Restricción , Adulto , Brasil , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/etnología , Factor de Necrosis Tumoral alfa/sangre , Población BlancaRESUMEN
OBJECTIVES: To determine whether disease activity verified by laboratorial parameters is associated with a higher frequency of hypertension in patients with systemic lupus erythematosus (SLE) without renal impairment and to investigate factors that could influence this hypertension. METHOD: This study included 102 controls, 70 patients with inactive SLE, and 53 patients with active SLE without renal impairment. We evaluated T helper type 1 (Th1)/Th2 lineage cytokines, nitric oxide (NO), insulin resistance (IR), and oxidative stress. RESULTS: Patients with active SLE had a higher probability of developing hypertension compared to controls [odds ratio (OR) 3.833, 95% confidence interval (CI) 1.806-8.137, p < 0.0003] and patients with inactive SLE (OR 2.215, 95% CI 1.032-4.752, p = 0.0394). Active SLE patients had a higher interleukin (IL)-12/IL-4 ratio (p < 0.05) than both controls and inactive SLE patients. Protein oxidation was significantly higher in patients with active SLE than in the control group and in patients with inactive SLE (p < 0.01 and p < 0.05, respectively). Multivariate analysis revealed an association between the presence of hypertension and he levels of glucose (p = 0.0276), insulin (p = 0.0498), hydroperoxides (p = 0.0221), IFN-γ (p = 0.0494), IL-17 (p = 0.0272), IL-12/IL-10 (p = 0.0373), IFN-γ/IL-10 (p = 0.0142), IFN-γ/IL-4 (p = 0.0320), and adiponectin (p = 0.0433). CONCLUSIONS: Patients with active SLE without renal impairment had an increased frequency of high blood pressure (43.4%) compared with patients with inactive SLE (25.7%) and controls (16.7%). Hypertension was associated with serologically active disease and was influenced by an increased Th1/Th2 ratio and oxidative stress.
Asunto(s)
Hipertensión/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Estrés Oxidativo/fisiología , Células TH1/metabolismo , Células Th2/metabolismo , Adulto , Glucemia/metabolismo , Citocinas/sangre , Femenino , Humanos , Hipertensión/inmunología , Hipertensión/metabolismo , Insulina/sangre , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Masculino , Persona de Mediana Edad , Células TH1/inmunología , Células Th2/inmunologíaRESUMEN
To determine the association of the HLA in 50 patients with schizophrenia, schizoaffective disorder, 48 healthy controls, 41 biological relatives without psychiatric disease, and 48 biological relatives with mood disorder, the HLA genotype at the class I and class II were determined. The subjects were interviewed by structured diagnostic criteria categorized according to DSM-IV, axis I, (SCID-IV). Significant positive association was found with HLA-B.15 in patients, family with humor disorder and without mental disorder (p=0.003) and negative association of the HLA-B.35 in relatives without psychiatric disease (p=0.03). The HLA-B.15 frequency was significantly increased in a subgroup of patients with age at onset in the early 20s, lower educational achievement, occupational disability, chronically ill, more paranoid type. These findings suggest the existence of some involvement of an immunogenetic mechanism in a subgroup of schizophrenic, schizoaffective patients, and biological relatives.
Asunto(s)
Antígenos HLA/inmunología , Trastornos Psicóticos/inmunología , Esquizofrenia/inmunología , Logro , Adulto , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Empleo , Familia , Femenino , Genotipo , Antígenos HLA-DR/inmunología , Humanos , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/genética , Esquizofrenia/diagnóstico , Esquizofrenia/genéticaRESUMEN
We studied cadaver kidney transplant recipients to determine if their serum levels of donor-specific class I sHLA correlated with graft outcome. Testing of sHLA was performed by an ELISA sandwich assay using allospecific monoclonal trapping antibodies and anti-beta2-mu detecting antibody. Sufficient sHLA sensitivity (<1 ng/ml) was achieved by using two synergistic trapping antibodies. Suitable antibodies were available for A2 and B7, and data were collected for these two antigens. Stability of these sHLA was determined in plasma and serum as were ranges of normal and background levels. Background levels varied substantially. Five A2- recipients of A2+ grafts and 5 B7- recipients of B7+ grafts were studied with appropriate sHLA levels measured pre-transplant and at intervals post-transplant. Graft outcome was assessed by serum creatinines, renal biopsies and/or therapy for rejection. In the 5 patients (3 A2- and 2 B7-) whose post-transplant donor-specific sHLA never exceeded immunological complications (e.g., post-operative ATN, ureteral obstruction) did not affect the correlation. In the 5 patients with post-transplant levels exceeding pre-transplant levels, subsequent evidence of rejection was observed. Periodic measurement of donor-specific sHLA should be a useful instrument for monitoring renal allograft rejection.