RESUMEN
HLA-DQA1*01:03:11 differs from HLA-DQA1*01:03:01:02 by one nucleotide substitution in codon 59 in exon 2.
Asunto(s)
Nucleótidos , Humanos , Alelos , Cadenas alfa de HLA-DQ/genética , Exones/genéticaRESUMEN
HLA-DRB1*04:04:20 differs from HLA-DRB1*04:04:01:04 by one nucleotide substitution in codon 135 in exon 3.
Asunto(s)
Nucleótidos , Humanos , Alelos , Exones/genética , Cadenas HLA-DRB1/genéticaRESUMEN
HLA-DRB4*01:01:12 differs from HLA-DRB4*01:01:01:01 by one nucleotide substitution in codon 175 in exon 3.
Asunto(s)
Alelos , Secuencia de Bases , Exones , Cadenas HLA-DRB4 , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Prueba de Histocompatibilidad/métodos , Análisis de Secuencia de ADN/métodos , Cadenas HLA-DRB4/genética , Codón , Alineación de SecuenciaRESUMEN
HLA-B*14:121 differs from HLA-B*14:01:01:01 by one nucleotide substitution in codon 319 in exon 6.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-B , Humanos , Alelos , Prueba de Histocompatibilidad , Codón , Antígenos HLA-B/genética , Análisis de Secuencia de ADNRESUMEN
HLA-C*05:286 differs from HLA-C*05:01:01:02 by one nucleotide substitution in codon 283 in exon 5.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Prueba de Histocompatibilidad , Codón , Análisis de Secuencia de ADNRESUMEN
HLA-B*51:394Q differs from HLA-B*51:01:01:05 by one nucleotide substitution in codon 339 in exon 7.
Asunto(s)
Antígenos HLA-B , Humanos , Alelos , Prueba de Histocompatibilidad , Codón , Antígenos HLA-B/genética , Análisis de Secuencia de ADNRESUMEN
HLA-C*01:263 differs from HLA-C*01:02:01:01 by one nucleotide substitution in codon 98 in exon 3.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Prueba de Histocompatibilidad , Codón , Análisis de Secuencia de ADNRESUMEN
HLA-DRB1*08:126 differs from HLA-DRB1*08:04:01:01 by one nucleotide substitution in codon 152 in exon 3.
Asunto(s)
Alelos , Secuencia de Bases , Exones , Cadenas HLA-DRB1 , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Cadenas HLA-DRB1/genética , Prueba de Histocompatibilidad/métodos , Análisis de Secuencia de ADN/métodos , Codón , Alineación de SecuenciaRESUMEN
HLA-DRB3*02:194 differs from HLA-DRB3*02:02:01:02 by one nucleotide substitution in codon 78 in exon 2.
Asunto(s)
Secuencia de Bases , Humanos , Cadenas HLA-DRB3/genética , Alelos , Prueba de Histocompatibilidad , Codón , Análisis de Secuencia de ADN , Cadenas HLA-DRB1RESUMEN
HLA-DQA1*05:112 differs from HLA-DQA1*05:05:01:01 by one nucleotide substitution in codon -7 in exon 1.
Asunto(s)
Alelos , Secuencia de Bases , Exones , Cadenas alfa de HLA-DQ , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Cadenas alfa de HLA-DQ/genética , Prueba de Histocompatibilidad/métodos , Análisis de Secuencia de ADN/métodos , Codón , Alineación de SecuenciaRESUMEN
ABSTRACT: Chronic graft-versus-host disease (cGVHD) is a debilitating, autoimmune-like syndrome that can occur after allogeneic hematopoietic stem cell transplantation. Constitutively activated B cells contribute to ongoing alloreactivity and autoreactivity in patients with cGVHD. Excessive tissue damage that occurs after transplantation exposes B cells to nucleic acids in the extracellular environment. Recognition of endogenous nucleic acids within B cells can promote pathogenic B-cell activation. Therefore, we hypothesized that cGVHD B cells aberrantly signal through RNA and DNA sensors such as Toll-like receptor 7 (TLR7) and TLR9. We found that B cells from patients and mice with cGVHD had higher expression of TLR7 than non-cGVHD B cells. Using ex vivo assays, we found that B cells from patients with cGVHD also demonstrated increased interleukin-6 production after TLR7 stimulation with R848. Low-dose B-cell receptor (BCR) stimulation augmented B-cell responses to TLR7 activation. TLR7 hyperresponsiveness in cGVHD B cells correlated with increased expression and activation of the downstream transcription factor interferon regulatory factor 5. Because RNA-containing immune complexes can activate B cells through TLR7, we used a protein microarray to identify RNA-containing antigen targets of potential pathological relevance in cGVHD. We found that many of the unique targets of active cGVHD immunoglobulin G (IgG) were nucleic acid-binding proteins. This unbiased assay identified the autoantigen and known cGVHD target Ro-52, and we found that RNA was required for IgG binding to Ro-52. Herein, we find that BCR-activated B cells have aberrant TLR7 signaling responses that promote potential effector responses in cGVHD.