@article{TEXTUAL,
      recid = {8556},
      author = {Xue, Jianmin and Gochuico, Bernadette R. and Alawad, Ahmad  Samer and Feghali-Bostwick, Carol A. and Noth, Imre and  Nathan, Steven D. and Rosen, Glenn D. and Rosas, Ivan O.  and Dacic, Sanja and Ocak, Iclal and Fuhrman, Carl R. and  Cuenco, Karen T. and Smith, Mary A. and Jacobs, Susan S.  and Zeevi, Adriana and Morel, Penelope A. and Pilewski,  Joseph M. and Valentine, Vincent G.},
      title = {The HLA Class II Allele DRB1*1501 Is Over-Represented in  Patients with Idiopathic Pulmonary Fibrosis},
      journal = {PLOS ONE},
      address = {2011-02-23},
      number = {TEXTUAL},
      abstract = {<p>Background: Idiopathic pulmonary fibrosis (IPF) is a  progressive and medically refractory lung disease with a  grim prognosis. Although the etiology of IPF remains  perplexing, abnormal adaptive immune responses are evident  in many afflicted patients. We hypothesized that  perturbations of human leukocyte antigen (HLA) allele  frequencies, which are often seen among patients with  immunologic diseases, may also be present in IPF  patients.</p><p>Methods/Principal Findings: HLA alleles  were determined in subpopulations of IPF and normal  subjects using molecular typing methods. HLA-DRB1*15 was  over-represented in a discovery cohort of 79 Caucasian IPF  subjects who had lung transplantations at the University of  Pittsburgh (36.7%) compared to normal reference  populations. These findings were prospectively replicated  in a validation cohort of 196 additional IPF subjects from  four other U.S. medical centers that included both  ambulatory patients and lung transplantation recipients.  High-resolution typing was used to further define specific  HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects  was similar among the 143 ambulatory patients and 132  transplant recipients (31.5% and 34.8%, respectively,  p = 0.55). The aggregate prevalence of DRB1*1501 in IPF  patients was significantly greater than among 285 healthy  controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI  1.3–2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91)  tended to have decreased diffusing capacities for carbon  monoxide (DL<sub>CO</sub>) compared to the 184 disease  subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%,  p = 0.036).</p><p>Conclusions/Significance: DRB1*1501 is  more prevalent among IPF patients than normal subjects, and  may be associated with greater impairment of gas exchange.  These data are novel evidence that immunogenetic processes  can play a role in the susceptibility to and/or  manifestations of IPF. Findings here of a disease  association at the HLA-DR locus have broad pathogenic  implications, illustrate a specific chromosomal area for  incremental, targeted genomic study, and may identify a  distinct clinical phenotype among patients with this  enigmatic, morbid lung disease.</p>},
      url = {http://knowledge.uchicago.edu/record/8556},
}