RESUMO
Anti-nuclear antibodies to speckled 100 kDa (sp100) and glycoprotein 210 (gp210) are specific serologic markers of primary biliary cholangitis (PBC) of uncertain/controversial clinical or prognostic significance. To study the genetic determinants associated with sp100 and gp210 autoantibody subphenotypes, we performed a genome-wide association analysis of 930 PBC cases based on their autoantibody status, followed by a replication study in 1,252 PBC cases. We confirmed single-nucleotide polymorphisms rs492899 (P = 3.27 × 10-22 ; odds ratio [OR], 2.90; 95% confidence interval [CI], 2.34-3.66) and rs1794280 (P = 5.78 × 10-28 ; OR, 3.89; 95% CI, 3.05-4.96) in the human major histocompatibility complex (MHC) region associated with the sp100 autoantibody. However, no genetic variant was identified as being associated with the gp210 autoantibody. To further define specific classical human leukocyte antigen (HLA) alleles or amino acids associated with the sp100 autoantibody, we imputed 922 PBC cases (211 anti-sp100-positive versus 711 negative cases) using a Han Chinese MHC reference database. Conditional analysis identified that HLA-DRß1-Asn77/Arg74, DRß1-Ser37, and DPß1-Lys65 were major determinants for sp100 production. For the classical HLA alleles, the strongest association was with DRB1*03:01 (P = 1.51 × 10-9 ; OR, 2.97; 95% CI, 2.06-4.29). Regression analysis with classical HLA alleles identified DRB1*03:01, DRB1*15:01, DRB1*01, and DPB1*03:01 alleles can explain most of the HLA association with sp100 autoantibody. Conclusion: This study indicated significant genetic predisposition to the sp100 autoantibody, but not the gp210 autoantibody, subphenotype in PBC patients. Additional studies will be necessary to determine if these findings have clinical significance to PBC pathogenesis and/or therapeutics.
Assuntos
Anticorpos Antinucleares/genética , Antígenos Nucleares/imunologia , Autoantígenos/imunologia , Cirrose Hepática Biliar/genética , Idoso , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Cirrose Hepática Biliar/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
The emergency treatment of thoracic injuries varies of general conditions and modern warfare. However, there are no unified battlefield treatment guidelines for thoracic injuries in the Chinese People's Liberation Army (PLA). An expert consensus has been reached based on the epidemiology of thoracic injuries and the concept of battlefield treatment combined with the existing levels of military medical care in modern warfare. Since there are no differences in the specialized treatment for thoracic injuries between general conditions and modern warfare, first aid, emergency treatment, and early treatment of thoracic injuries are introduced separately in three levels in this consensus. At Level I facilities, tension pneumothorax and open pneumothorax are recommended for initial assessment during the first aid stage. Re-evaluation and further treatment for hemothorax, flail chest, and pericardial tamponade are recommended at Level II facilities. At Level III facilities, simple surgical operations such as emergency thoracotomy and debridement surgery for open pneumothorax are recommended. The grading standard for evidence evaluation and recommendation was used to reach this expert consensus.