RESUMEN
OBJECTIVE: To determine the association between endoplasmic reticulum aminopeptidase (ERAP)1 and ERAP2 single-nucleotide polymorphisms (SNPs) and human leukocyte antigens (HLA)-B27+ or HLA-B15+ patients with spondyloarthritis (SpA). METHODS: 104 patients with SpA according to Assessment of Spondyloarthritis International Society criteria were included in the study. HLA typing was performed by PCR. The polymorphisms were determined by real-time PCR on genomic DNA using customised probes for SNPs rs27044, rs17482078, rs10050860 and rs30187 in ERAP1, and rs2910686, rs2248374 and rs2549782 in ERAP2. RESULTS: 70 of the104 patients with SpA were HLA-B27+ and 34 were HLA-B15+. The distribution of ERAP1 and ERAP2 SNPs between the HLA-B15+ and HLA-B27+ patients with SpA did not reveal differences. Likewise, no differences in the frequencies of ERAP1 SNP haplotypes and alleles HLA-B15 or HLA-B27 were found. Interestingly, however, the frequencies of three particular haplotypes formed by ERAP2 SNPs rs2549782/rs2248374/rs2910686 varied between HLA-B15+ and HLA-B27+ patients: the ERAP2 SNPs haplotype TGT was more common in HLA-B15+ patients with SpA (OR 2.943, 95% CI 1.264 to 6.585; P=0.009), whereas the ERAP2 SNP haplotypes TGC and CAT were more associated with HLA-B27+ patients with SpA: (OR 4.483, 95% CI 1.524 to 13.187; p=0.003) and (OR 9.014, 95% CI 1.181 to 68.807; p=0.009), respectively. CONCLUSION: An association was found between HLA-B15+ patients with SpA and haplotype TGT of ERAP2 SNPs. On the other hand, HLA-B27+ patients with SpA were associated with ERAP2 haplotypes TGC and CAT. These associations could be related to the clinical presentation of the disease, specifically with a peripheral or axial predominance, respectively.
Asunto(s)
Aminopeptidasas/genética , Predisposición Genética a la Enfermedad , Antígeno HLA-B15/genética , Antígeno HLA-B27/genética , Polimorfismo de Nucleótido Simple , Espondiloartritis/diagnóstico , Espondiloartritis/etiología , Adulto , Alelos , Autoinmunidad , Biomarcadores/sangre , Biomarcadores/metabolismo , Colombia , Citocinas/sangre , Citocinas/metabolismo , Femenino , Estudios de Asociación Genética , Genotipo , Antígeno HLA-B15/inmunología , Antígeno HLA-B27/inmunología , Prueba de Histocompatibilidad , Humanos , Mediadores de Inflamación , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fenotipo , Radiografía , Espondiloartritis/metabolismoRESUMEN
Characterization of an HLA-B*15:10:01 variant, HLA-B*15:10:01:05.
Asunto(s)
Antígeno HLA-B15/genética , Polimorfismo de Nucleótido Simple , Obtención de Tejidos y Órganos , Regiones no Traducidas 3'/genética , Alelos , Trasplante de Médula Ósea , Brasil , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Análisis de Secuencia de ADNRESUMEN
Characterization of the first HLA-B*15:31 variant, called HLA-B*15:31:01:02.
Asunto(s)
Antígeno HLA-B15/genética , Polimorfismo de Nucleótido Simple , Obtención de Tejidos y Órganos , Alelos , Trasplante de Médula Ósea , Brasil , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Intrones/genética , Masculino , Análisis de Secuencia de ADNRESUMEN
There is substantial evidence that non-B27 major histocompatibility complex (MHC) genes are associated with spondyloarthritis (SpA). Studies in Mexican and Tunisian populations demonstrated the association of SpA and human leukocyte antigen (HLA) B15. The purpose of this study was to evaluate the association of HLA-A, B, and DR antigens in a group of Colombian patients with a diagnosis of SpA. A total of 189 patients and 100 healthy subjects were included in the present study. All subjects underwent a complete characterization of HLA alleles A, B, and DR. Of the 189 studied patients, 35 were reactive arthritis (ReA), 87 were ankylosing spondylitis (AS), and 67 undifferentiated SpA (uSpA). According to the Assessment of Spondyloarthritis International Society (ASAS) criteria, 167 were axial SpA (axSpA) and 171 were peripheral SpA (pSpA). 63.8% were men, with a mean age of 35.9 ± 12.7 years. 40.7% (77/189) of patients were HLA-B27 positive of which 52.9% had AS and 42.5% axSpA. 23.2% (44/189) of patients were HLA-B15 positive: 23.8% were uSpA, 12.57% were axSpA, and 11.7% were pSpA. In addition, HLA-DRB1*01 was associated with AS (58.6%) and axSpA (42.5%). Also, HLA-DRB1*04 was present in 62 patients with AS (71.2%) and in 26 with axSpA (15.5%). In this population, we found a strong association between the presence of HLA-B27 and the diagnosis of axSpA and AS, but the HLA-B15 is also significantly associated with all subtypes of the disease, predominantly with pSpA. Additionally, HLA-DR1 and DR4 were associated in a cohort of patients with SpA from Colombia.
Asunto(s)
Artritis Reactiva/genética , Antígeno HLA-B15/genética , Antígeno HLA-B27/genética , Cadenas HLA-DRB1/genética , Espondilitis Anquilosante/genética , Adulto , Artritis Reactiva/diagnóstico , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Humanos , Masculino , México , Persona de Mediana Edad , Prohibitinas , Espondilitis Anquilosante/diagnóstico , Adulto JovenRESUMEN
HLA-B*15:04:04 differs from HLA-B*15:04:01 by one nucleotide at codon 238 (gat > gac).
Asunto(s)
Alelos , Donantes de Sangre , Exones , Antígeno HLA-B15/genética , Ensayos de Aptitud de Laboratorios/normas , Mutación Puntual , Secuencia de Bases , Transfusión Sanguínea , Brasil , Codón/química , Antígeno HLA-B15/inmunología , Haplotipos , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: Human leucocyte antigen (HLA) B27 and HLA-B15 are associated with spondyloarthritis (SpA). Recent Assessment of SpondyloArthritis international Society (ASAS) criteria emphasise a distinction between SpA with axial and peripheral patterns. We analysed whether HLA-A, HLA-B and HLA-DRB1 alleles could associate with these patterns. METHODS: We studied 100 healthy individuals and 178 patients with SpA according to European Spondyloarthropathy Study Group (ESSG) criteria. Patients were then classified according to ASAS criteria, the axial spondyloarthritis pattern (axSpA) being defined by ascertained sacroiliitis and the peripheral pattern (pSpA) by enthesitis and/or arthritis in extremities. A combined ax/p pattern was also considered. RESULTS: Only HLA-B27 and HLA-B15 alleles were associated with SpA. ASAS criteria for axSpA were met in 152 patients (12 with isolated axSpA and 140 with a combined ax/p patterns). When the ASAS peripheral criteria were applied, 161 patients met these criteria (13 with isolated pSpA and 148 with a combined ax/p pattern). HLA-B27 was found in 83% of patients with axSpA and 43% of ax/pSpA patients according to axASAS. HLA-B27 occurred in 7% controls but not in any patient with isolated pSpA. HLA-B15 was encountered in 31% of patients with isolated pSpA and 20% of ax/pSpA patients according to pASAS criteria. Moreover, 2 healthy controls, but none of our patients with isolated axSpA were positive for HLA-B15. CONCLUSIONS: Our data suggest that the presence of HLA-B15 favours the development of isolated/combined peripheral rather than isolated axSpA, while HLA-B27 promotes an isolated/combined axial disease and excludes a peripheral pattern. HLA-B15 should be considered in addition to HLA-B27 when diagnosing patients with SpA according to ASAS criteria.
Asunto(s)
Antígeno HLA-B15/genética , Antígeno HLA-B27/genética , Espondiloartritis/clasificación , Espondiloartritis/genética , Adulto , Femenino , Genotipo , Humanos , MasculinoRESUMEN
HLA-A*02:481 differs from HLA-A*02:01:01:01 by one nucleotide and was found in four unrelated Brazilians.