Limits...
The HLA class II Allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis.

Xue J, Gochuico BR, Alawad AS, Feghali-Bostwick CA, Noth I, Nathan SD, Rosen GD, Rosas IO, Dacic S, Ocak I, Fuhrman CR, Cuenco KT, Smith MA, Jacobs SS, Zeevi A, Morel PA, Pilewski JM, Valentine VG, Gibson KF, Kaminski N, Sciurba FC, Zhang Y, Duncan SR - PLoS ONE (2011)

Bottom Line: 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).DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

ABSTRACT

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.

Show MeSH

Related in: MedlinePlus

Associations of DRB1*1501 and lung function.A.) Forced vital capacities, as percentages of predicted normal values (FVC%predicted), did not show a consistent association with the presence or absence of DRB1*1501 among the IPF subjects. Aggregate mean values are denoted by horizontal bars linked by dashed lines. B.) Diffusing capacities, as percentages of predicted normal values (DLCO%predicted), were decreased among those IPF subjects with DRB1*1501 vs. those patients who did not have this allele, at each participating center. These differences were significant in comparisons of the cumulative (aggregate) IPF populations, despite considerable overall differences of DLCO%predicted values (e.g., “noise”) between the various participating medical centers (see also Table 1).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3044131&req=5

pone-0014715-g002: Associations of DRB1*1501 and lung function.A.) Forced vital capacities, as percentages of predicted normal values (FVC%predicted), did not show a consistent association with the presence or absence of DRB1*1501 among the IPF subjects. Aggregate mean values are denoted by horizontal bars linked by dashed lines. B.) Diffusing capacities, as percentages of predicted normal values (DLCO%predicted), were decreased among those IPF subjects with DRB1*1501 vs. those patients who did not have this allele, at each participating center. These differences were significant in comparisons of the cumulative (aggregate) IPF populations, despite considerable overall differences of DLCO%predicted values (e.g., “noise”) between the various participating medical centers (see also Table 1).

Mentions: There were no apparent associations between the presence (n = 91) or absence (n = 184) of DRB1*1501 among the IPF patients and either age (66±1 vs. 67±1 years) or gender (75% vs. 73% males), for the DRB1*1501+ and DRB1*1501 subjects, respectively. Similarly, FVC%p did not consistently differ between the IPF patients with and without DRB1*1501 (Figure 2A).


The HLA class II Allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis.

Xue J, Gochuico BR, Alawad AS, Feghali-Bostwick CA, Noth I, Nathan SD, Rosen GD, Rosas IO, Dacic S, Ocak I, Fuhrman CR, Cuenco KT, Smith MA, Jacobs SS, Zeevi A, Morel PA, Pilewski JM, Valentine VG, Gibson KF, Kaminski N, Sciurba FC, Zhang Y, Duncan SR - PLoS ONE (2011)

Associations of DRB1*1501 and lung function.A.) Forced vital capacities, as percentages of predicted normal values (FVC%predicted), did not show a consistent association with the presence or absence of DRB1*1501 among the IPF subjects. Aggregate mean values are denoted by horizontal bars linked by dashed lines. B.) Diffusing capacities, as percentages of predicted normal values (DLCO%predicted), were decreased among those IPF subjects with DRB1*1501 vs. those patients who did not have this allele, at each participating center. These differences were significant in comparisons of the cumulative (aggregate) IPF populations, despite considerable overall differences of DLCO%predicted values (e.g., “noise”) between the various participating medical centers (see also Table 1).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3044131&req=5

pone-0014715-g002: Associations of DRB1*1501 and lung function.A.) Forced vital capacities, as percentages of predicted normal values (FVC%predicted), did not show a consistent association with the presence or absence of DRB1*1501 among the IPF subjects. Aggregate mean values are denoted by horizontal bars linked by dashed lines. B.) Diffusing capacities, as percentages of predicted normal values (DLCO%predicted), were decreased among those IPF subjects with DRB1*1501 vs. those patients who did not have this allele, at each participating center. These differences were significant in comparisons of the cumulative (aggregate) IPF populations, despite considerable overall differences of DLCO%predicted values (e.g., “noise”) between the various participating medical centers (see also Table 1).
Mentions: There were no apparent associations between the presence (n = 91) or absence (n = 184) of DRB1*1501 among the IPF patients and either age (66±1 vs. 67±1 years) or gender (75% vs. 73% males), for the DRB1*1501+ and DRB1*1501 subjects, respectively. Similarly, FVC%p did not consistently differ between the IPF patients with and without DRB1*1501 (Figure 2A).

Bottom Line: 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).DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus