Nickerson C L, Luthra H S, David C S
Department of Immunology, Mayo Clinic, Rochester, MN 55905.
Ann Rheum Dis. 1990 Jun;49 Suppl 1:426-33.
Several MHC (major histocompatibility complex) genes are associated with increased incidence of disease. The strongest association is between the class I gene, HLA-B27, and ankylosing spondylitis (AS). HLA-B27 is also highly associated with Reiter's syndrome. As not all subjects with HLA-B27 develop AS or Reiter's syndrome, environmental factors may have a key role in the pathogenesis of these arthritic diseases. Several studies have implicated klebsiella in the development of AS, whereas Reiter's syndrome may result from infection with yersinia, shigella, salmonella, campylobacter, or chlamydia. Transgenic mice present a unique opportunity to study the association of specific MHC genes and disease. HLA-B27 transgenic mice were produced to study the association of HLA-B27, bacterial infection, and arthritic disease. Mice with the HLA-B27 gene are more susceptible to intravenous infection with Yersinia enterocolitica 0:8 WA than negative litter mates as shown by a higher incidence of spinal abscesses and mortality. Understanding the mechanism(s) responsible for this difference may yield valuable insights into the pathogenesis of HLA-B27 associated disease in humans.
几种主要组织相容性复合体(MHC)基因与疾病发病率增加相关。最强的关联存在于I类基因HLA - B27与强直性脊柱炎(AS)之间。HLA - B27也与赖特综合征高度相关。由于并非所有携带HLA - B27的个体都会患上AS或赖特综合征,环境因素可能在这些关节炎疾病的发病机制中起关键作用。多项研究表明克雷伯菌与AS的发病有关,而赖特综合征可能由耶尔森菌、志贺菌、沙门菌、弯曲杆菌或衣原体感染引起。转基因小鼠为研究特定MHC基因与疾病的关联提供了独特的机会。为了研究HLA - B27、细菌感染和关节炎疾病之间的关联,人们培育出了HLA - B27转基因小鼠。携带HLA - B27基因的小鼠比同窝阴性小鼠更容易受到小肠结肠炎耶尔森菌0:8 WA的静脉感染,表现为脊柱脓肿和死亡率更高。了解造成这种差异的机制可能会为人类HLA - B27相关疾病的发病机制提供有价值的见解。