Articles |

Sarcoidosis*: Association With Human Leukocyte Antigen Class II Amino Acid Epitopes and Interaction With Environmental Exposures FREE TO VIEW

Milton Rossman, MD; Bruce Thompson, PhD; Margaret Frederick, PhD; Boyani Cizman, PhD; Eleni Magira, MD; Dimitri Monos, PhD
Author and Funding Information

*From the Hospital of the University of Pennsylvania (Dr. Rossman), Philadelphia, PA; Clinical Trials & Surveys Corp (Drs. Thompson and Frederick), Baltimore, MD; and the Children’s Hospital of Philadelphia (Drs. Cizman, Magira, and Monos), Philadelphia, PA.

Correspondence to: Milton Rossman, MD, Department of Pulmonary Medicine, University of Pennsylvania, 421 Curie Blvd, 851 BRB II/III, Philadelphia, PA 19104-6160.

Chest. 2002;121(3_suppl):14S. doi:10.1378/chest.121.3_suppl.14S
Text Size: A A A
Published online

S arcoidosis is believed to be a hypersensitivity to unknown environmental agents that is mediated by CD4+ T cells. Since CD4+ T cells recognize peptide ligands from environmental agents that are presented to them by human leukocyte antigen (HLA) class II molecules, the affinity of HLA class II molecules for these ligands may be a determinant of the susceptibility to sarcoidosis. Blood was obtained from 474 case-control pairs from A Case-Control Etiologic Study of Sarcoidosis (ACCESS) study for HLA studies. Control subjects were pair-matched for age, sex, and self-designated race. DNA was extracted and analyzed for HLA DRB1, DQB1, and DPB1 alleles and for the presence of group DRB3, DRB4, or DRB5 alleles using a sequence-specific oligonucleotide probe and sequence-specific primer techniques. Statistical analyses were based on the proportion of informative pairs among cases and control subjects. We tested globally for significance in each of the following regions: DRB1 (53 alleles); DQB1 (19 alleles); and DPB1 (41 alleles). DRB1 was significantly associated with the entire cohort, African Americans (AAs) and whites (p < 0.0001, p < 0.009, and p < 0.001, respectively) for each group, and DPB1 was only significantly associated with AAs (p < 0.04). In addition, the presence of a DRB3 allele was significantly associated with the entire cohort and AAs (p < 0.01 and p < 0.01, respectively), the presence of a DRB4 allele was associated with the control subjects in the entire cohort, AAs, and whites (p < 0.01, p < 0.04, and p < 0.07, respectively), and the presence of a DRB5 allele was associated with control subjects in AAs (p < 0.03) but with sarcoidosis in whites (p < 0.01). Using logistic regression, among AAs three amino acid epitopes were significantly (p < 0.05) associated with sarcoidosis (DRB1 R71, F47, and DPB1 V76), and three were associated with the control population (DRB1 Q10, Y26, and DQB1 E74). In the white population, five amino acid epitopes were associated with sarcoidosis (DRB1 F47, A71, R70, DQB1 A57, and DPB1 F35), while two were associated with control subjects (DRB1 Q70 and DPB1 I65). These amino acid epitopes were tested for interactions with specific environmental and occupational exposures. Significant (p < 0.05) interactions were detected that either increased or decreased the risk for sarcoidosis. The results of these studies indicate that environmental and genetic factors interact in the predisposition for sarcoidosis and support the notion that sarcoidosis occurs after environmental exposures in a genetically susceptible population.

Abbreviations: AA = African American; HLA = human leukocyte antigen

This research was supported by National Heart, Lung, and Blood Institute Contracts NO1-HR-56065, 56066, 56067, 56068, 56069, 56070, 56071, 56072, 56073, 56074, and 56075.




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543