The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis
Publication Date
February 23, 2011
Journal
PLOS ONE
Authors
Jianmin Xue, Bernadette R. Gochuico, Ahmad Samer Alawad, Carol A. Feghali Bostwick, et al
Volume
6
Issue
2
Pages
e14715
DOI
https://dx.plos.org/10.1371/journal.pone.0014715
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0014715
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/21373184
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044131
Europe PMC
http://europepmc.org/abstract/MED/21373184
Web of Science
000287657500003
Scopus
79952009858
Mendeley
http://www.mendeley.com/research/hla-class-ii-allele-drb11501-overrepresented-patients-idiopathic-pulmonary-fibrosis-2
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Mendeley | Further Information

{"title"=>"The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis", "type"=>"journal", "authors"=>[{"first_name"=>"Jianmin", "last_name"=>"Xue", "scopus_author_id"=>"8519864400"}, {"first_name"=>"Bernadette R.", "last_name"=>"Gochuico", "scopus_author_id"=>"6602363685"}, {"first_name"=>"Ahmad Samer", "last_name"=>"Alawad", "scopus_author_id"=>"40560946800"}, {"first_name"=>"Carol A.", "last_name"=>"Feghali-Bostwick", "scopus_author_id"=>"55666589500"}, {"first_name"=>"Imre", "last_name"=>"Noth", "scopus_author_id"=>"6508328036"}, {"first_name"=>"Steven D.", "last_name"=>"Nathan", "scopus_author_id"=>"7005532622"}, {"first_name"=>"Glenn D.", "last_name"=>"Rosen", "scopus_author_id"=>"35793972400"}, {"first_name"=>"Ivan O.", "last_name"=>"Rosas", "scopus_author_id"=>"16418008900"}, {"first_name"=>"Sanja", "last_name"=>"Dacic", "scopus_author_id"=>"56575670400"}, {"first_name"=>"Iclal", "last_name"=>"Ocak", "scopus_author_id"=>"16231039300"}, {"first_name"=>"Carl R.", "last_name"=>"Fuhrman", "scopus_author_id"=>"7005624812"}, {"first_name"=>"Karen T.", "last_name"=>"Cuenco", "scopus_author_id"=>"6506157707"}, {"first_name"=>"Mary A.", "last_name"=>"Smith", "scopus_author_id"=>"55574214708"}, {"first_name"=>"Susan S.", "last_name"=>"Jacobs", "scopus_author_id"=>"15020746600"}, {"first_name"=>"Adriana", "last_name"=>"Zeevi", "scopus_author_id"=>"7102794825"}, {"first_name"=>"Penelope A.", "last_name"=>"Morel", "scopus_author_id"=>"7202417595"}, {"first_name"=>"Joseph M.", "last_name"=>"Pilewski", "scopus_author_id"=>"7004250270"}, {"first_name"=>"Vincent G.", "last_name"=>"Valentine", "scopus_author_id"=>"7003857529"}, {"first_name"=>"Kevin F.", "last_name"=>"Gibson", "scopus_author_id"=>"7202666589"}, {"first_name"=>"Naftali", "last_name"=>"Kaminski", "scopus_author_id"=>"7005152640"}, {"first_name"=>"Frank C.", "last_name"=>"Sciurba", "scopus_author_id"=>"7003987414"}, {"first_name"=>"Yingze", "last_name"=>"Zhang", "scopus_author_id"=>"55739972400"}, {"first_name"=>"Steven R.", "last_name"=>"Duncan", "scopus_author_id"=>"56744127600"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "doi"=>"10.1371/journal.pone.0014715", "sgr"=>"79952009858", "scopus"=>"2-s2.0-79952009858", "pmid"=>"21373184", "pui"=>"361332443"}, "id"=>"0d7291ac-ed2b-37a6-a305-ab33ec98e3ae", "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.\\n\\nMETHODS/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).\\n\\nCONCLUSIONS/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.", "link"=>"http://www.mendeley.com/research/hla-class-ii-allele-drb11501-overrepresented-patients-idiopathic-pulmonary-fibrosis-2", "reader_count"=>18, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Other"=>5, "Student > Master"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Other"=>5, "Student > Master"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>9, "Agricultural and Biological Sciences"=>3, "Computer Science"=>2, "Nursing and Health Professions"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Computer Science"=>{"Computer Science"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>1, "Mexico"=>1}, "group_count"=>3}

Scopus | Further Information

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  • {"files"=>["https://ndownloader.figshare.com/files/795979"], "description"=>"<p>*included patients with other autoimmune syndromes. Approximately fifty (50) HLA-A, 85 HLA-B, 45 HLA-C, 44 HLA-DR, and 16 HLA-DQ distinct polymorphisms (alleles and suballeles) are currently known to be expressed in Caucasian populations <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014715#pone.0014715-National1\" target=\"_blank\">[29]</a>.</p>", "links"=>[], "tags"=>["studies", "hla", "allele", "frequencies"], "article_id"=>466311, "categories"=>["Medicine", "Immunology"], "users"=>["Jianmin Xue", "Bernadette R. Gochuico", "Ahmad Samer Alawad", "Carol A. Feghali-Bostwick", "Imre Noth", "Steven D. Nathan", "Glenn D. Rosen", "Ivan O. Rosas", "Sanja Dacic", "Iclal Ocak", "Carl R. Fuhrman", "Karen T. Cuenco", "Mary A. Smith", "Susan S. Jacobs", "Adriana Zeevi", "Penelope A. Morel", "Joseph M. Pilewski", "Vincent G. Valentine", "Kevin F. Gibson", "Naftali Kaminski", "Frank C. Sciurba", "Yingze Zhang", "Steven R. Duncan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014715.t004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Published_studies_of_HLA_allele_frequencies_in_IPF_/466311", "title"=>"Published studies of HLA allele frequencies in IPF.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 20:20:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/795783"], "description"=>"<p>DRB1*1501 was significantly over-represented in the cumulative IPF population (n = 275) compared to healthy controls (n = 285).</p>", "links"=>[], "tags"=>["prevalence", "ipf"], "article_id"=>466108, "categories"=>["Medicine", "Immunology"], "users"=>["Jianmin Xue", "Bernadette R. Gochuico", "Ahmad Samer Alawad", "Carol A. Feghali-Bostwick", "Imre Noth", "Steven D. Nathan", "Glenn D. Rosen", "Ivan O. Rosas", "Sanja Dacic", "Iclal Ocak", "Carl R. Fuhrman", "Karen T. Cuenco", "Mary A. Smith", "Susan S. Jacobs", "Adriana Zeevi", "Penelope A. Morel", "Joseph M. Pilewski", "Vincent G. Valentine", "Kevin F. Gibson", "Naftali Kaminski", "Frank C. Sciurba", "Yingze Zhang", "Steven R. Duncan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014715.g001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DRB1_1501_prevalence_in_IPF_and_controls_/466108", "title"=>"DRB1*1501 prevalence in IPF and controls.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 20:19:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/795883"], "description"=>"<p>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 (DL<sub>CO</sub>%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 DL<sub>CO</sub>%predicted values (e.g., “noise”) between the various participating medical centers (see also <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014715#pone-0014715-t001\" target=\"_blank\">Table 1</a>).</p>", "links"=>[], "tags"=>["immunology/genetics of the immune system", "immunology/immune response", "respiratory medicine/interstitial lung diseases"], "article_id"=>466226, "categories"=>["Medicine", "Immunology"], "users"=>["Jianmin Xue", "Bernadette R. Gochuico", "Ahmad Samer Alawad", "Carol A. Feghali-Bostwick", "Imre Noth", "Steven D. Nathan", "Glenn D. Rosen", "Ivan O. Rosas", "Sanja Dacic", "Iclal Ocak", "Carl R. Fuhrman", "Karen T. Cuenco", "Mary A. Smith", "Susan S. Jacobs", "Adriana Zeevi", "Penelope A. Morel", "Joseph M. Pilewski", "Vincent G. Valentine", "Kevin F. Gibson", "Naftali Kaminski", "Frank C. Sciurba", "Yingze Zhang", "Steven R. Duncan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014715.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Associations_of_DRB1_1501_and_lung_function_/466226", "title"=>"Associations of DRB1*1501 and lung function.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 20:19:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/796117"], "description"=>"<p>HLA allele prevalences (the percentages of subjects with one or more copies of the allele) in the initial U. Pgh. IPF transplant recipient population (n = 79) were compared to those of a normal reference population (n = 196). DRB1*15 was the most over-represented of the common HLA Class II alleles among the IPF (bold) relative to the controls. These initial findings prompted further study by recruitments of IPF validation cohorts from four other medical centers and high resolution typing of the DRB1*15 allele (see text).</p>", "links"=>[], "tags"=>["ii", "allele", "prevalence", "ipf"], "article_id"=>466455, "categories"=>["Medicine", "Immunology"], "users"=>["Jianmin Xue", "Bernadette R. Gochuico", "Ahmad Samer Alawad", "Carol A. Feghali-Bostwick", "Imre Noth", "Steven D. Nathan", "Glenn D. Rosen", "Ivan O. Rosas", "Sanja Dacic", "Iclal Ocak", "Carl R. Fuhrman", "Karen T. Cuenco", "Mary A. Smith", "Susan S. Jacobs", "Adriana Zeevi", "Penelope A. Morel", "Joseph M. Pilewski", "Vincent G. Valentine", "Kevin F. Gibson", "Naftali Kaminski", "Frank C. Sciurba", "Yingze Zhang", "Steven R. Duncan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014715.t002", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HLA_Class_II_Allele_Prevalence_in_the_Initial_IPF_Cohort_/466455", "title"=>"HLA Class II Allele Prevalence in the Initial IPF Cohort.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 20:21:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/796188"], "description"=>"<p>Parentheses denote percentages within respective control and IPF subject cohorts. *denotes p values for the 3×2 chi-square comparisons of the three genotype distributions among controls vs. IPF within the discovery or replication cohorts, respectively. The p value of the cumulative 3×2 chi-square comparison (the three genotype group distributions among all controls vs. all IPF subjects) is 0.0015.</p>", "links"=>[], "tags"=>["immunology/genetics of the immune system", "immunology/immune response", "respiratory medicine/interstitial lung diseases"], "article_id"=>466520, "categories"=>["Medicine", "Immunology"], "users"=>["Jianmin Xue", "Bernadette R. Gochuico", "Ahmad Samer Alawad", "Carol A. Feghali-Bostwick", "Imre Noth", "Steven D. Nathan", "Glenn D. Rosen", "Ivan O. Rosas", "Sanja Dacic", "Iclal Ocak", "Carl R. Fuhrman", "Karen T. Cuenco", "Mary A. Smith", "Susan S. Jacobs", "Adriana Zeevi", "Penelope A. Morel", "Joseph M. Pilewski", "Vincent G. Valentine", "Kevin F. Gibson", "Naftali Kaminski", "Frank C. Sciurba", "Yingze Zhang", "Steven R. Duncan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014715.t003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genotype_distribution_of_DRB1_1501_/466520", "title"=>"Genotype distribution of DRB1*1501.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 20:21:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/796049"], "description"=>"<p>Tx: transplant recipients; Amb: ambulatory clinic outpatients; hx: history. U.Pgh. Tx includes the 79 subjects of the initial discovery cohort, as well as an additional 19 recipients of lung transplantations for end-stage IPF that have occurred at that institution since the initial discovery compilation. FVC%p denotes forced vital capacity, as a percentage of predicted normal values; DL<sub>CO</sub>%p denotes diffusing capacity for carbon monoxide as a percentage of predicted normal values. Values among U. Pgh. Tx, Inova, and Stanford subjects are based on last determinations immediately prior to their lung transplantations.</p><p>*<0.003 for U. Pgh. (both Tx. and OP) and/or U. Chicago vs. all others;</p><p>**<0.003 for NIH vs. all other groups; U. Pgh. Tx vs. all Amb subpopulations.</p><p>***p<0.004 for NIH vs. all Tx cohorts, U. Pgh. Tx vs. all Amb groups.</p>", "links"=>[], "tags"=>["immunology/genetics of the immune system", "immunology/immune response", "respiratory medicine/interstitial lung diseases"], "article_id"=>466386, "categories"=>["Medicine", "Immunology"], "users"=>["Jianmin Xue", "Bernadette R. Gochuico", "Ahmad Samer Alawad", "Carol A. Feghali-Bostwick", "Imre Noth", "Steven D. Nathan", "Glenn D. Rosen", "Ivan O. Rosas", "Sanja Dacic", "Iclal Ocak", "Carl R. Fuhrman", "Karen T. Cuenco", "Mary A. Smith", "Susan S. Jacobs", "Adriana Zeevi", "Penelope A. Morel", "Joseph M. Pilewski", "Vincent G. Valentine", "Kevin F. Gibson", "Naftali Kaminski", "Frank C. Sciurba", "Yingze Zhang", "Steven R. Duncan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0014715.t001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IPF_Subject_Characteristics_/466386", "title"=>"IPF Subject Characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 20:20:49"}

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