PMID- 21373184
OWN - NLM
STAT- MEDLINE
DCOM- 20110901
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 2
DP  - 2011 Feb 23
TI  - The HLA class II Allele DRB1*1501 is over-represented in patients with idiopathic 
      pulmonary fibrosis.
PG  - e14715
LID - 10.1371/journal.pone.0014715 [doi]
LID - e14715
AB  - 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. 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(CO)) compared to the 184 disease subjects who lacked this allele 
      (37.8+/-1.7% vs. 42.8+/-1.4%, p = 0.036). 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.
FAU - Xue, Jianmin
AU  - Xue J
AD  - Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 
      United States of America.
FAU - Gochuico, Bernadette R
AU  - Gochuico BR
FAU - Alawad, Ahmad Samer
AU  - Alawad AS
FAU - Feghali-Bostwick, Carol A
AU  - Feghali-Bostwick CA
FAU - Noth, Imre
AU  - Noth I
FAU - Nathan, Steven D
AU  - Nathan SD
FAU - Rosen, Glenn D
AU  - Rosen GD
FAU - Rosas, Ivan O
AU  - Rosas IO
FAU - Dacic, Sanja
AU  - Dacic S
FAU - Ocak, Iclal
AU  - Ocak I
FAU - Fuhrman, Carl R
AU  - Fuhrman CR
FAU - Cuenco, Karen T
AU  - Cuenco KT
FAU - Smith, Mary A
AU  - Smith MA
FAU - Jacobs, Susan S
AU  - Jacobs SS
FAU - Zeevi, Adriana
AU  - Zeevi A
FAU - Morel, Penelope A
AU  - Morel PA
FAU - Pilewski, Joseph M
AU  - Pilewski JM
FAU - Valentine, Vincent G
AU  - Valentine VG
FAU - Gibson, Kevin F
AU  - Gibson KF
FAU - Kaminski, Naftali
AU  - Kaminski N
FAU - Sciurba, Frank C
AU  - Sciurba FC
FAU - Zhang, Yingze
AU  - Zhang Y
FAU - Duncan, Steven R
AU  - Duncan SR
LA  - eng
GR  - 1R01HL073241/HL/NHLBI NIH HHS/United States
GR  - 1P50 HL084948/HL/NHLBI NIH HHS/United States
GR  - P50 HL084948/HL/NHLBI NIH HHS/United States
GR  - 5T32 HL007563/HL/NHLBI NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - P50 HL084932/HL/NHLBI NIH HHS/United States
GR  - R01 HL073241/HL/NHLBI NIH HHS/United States
GR  - 1P50 HL084932/HL/NHLBI NIH HHS/United States
GR  - T32 HL007563/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20110223
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*15:01 antigen)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Aged
MH  - Alleles
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Female
MH  - Gene Frequency
MH  - Genetic Linkage
MH  - Genetic Predisposition to Disease
MH  - HLA-DR Antigens/*genetics
MH  - HLA-DRB1 Chains
MH  - Histocompatibility Antigens Class II/genetics
MH  - Humans
MH  - Idiopathic Pulmonary Fibrosis/epidemiology/*genetics
MH  - Male
MH  - Middle Aged
MH  - Prevalence
PMC - PMC3044131
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/03/05 06:00
MHDA- 2011/09/02 06:00
PMCR- 2011/02/23
CRDT- 2011/03/05 06:00
PHST- 2010/07/11 00:00 [received]
PHST- 2011/01/26 00:00 [accepted]
PHST- 2011/03/05 06:00 [entrez]
PHST- 2011/03/05 06:00 [pubmed]
PHST- 2011/09/02 06:00 [medline]
PHST- 2011/02/23 00:00 [pmc-release]
AID - 10-PONE-RA-20923R2 [pii]
AID - 10.1371/journal.pone.0014715 [doi]
PST - epublish
SO  - PLoS One. 2011 Feb 23;6(2):e14715. doi: 10.1371/journal.pone.0014715.