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Fibrosing mediastinitis complicating prior histoplasmosis is associated with human leukocyte antigen DQB1*04:02 − a case control study

Strock, S.B., Gaudieri, S., Mallal, S., Yu, C., Mitchell, D., Cogan, J., Mason, W., Crowe, D. and Loyd, J.E. (2015) Fibrosing mediastinitis complicating prior histoplasmosis is associated with human leukocyte antigen DQB1*04:02 − a case control study. BMC Infectious Diseases, 15 (1).

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Abstract

Background
Fibrosing mediastinitis (FM) is an idiosyncratic reaction to infection with Histoplasma capsulatum with a prevalence of 3:100,000 people infected. The rarity of post-histoplasmosis fibrosing mediastinitis (PHFM) in areas where H. capsulatum is endemic suggests that an abnormal immunological host response may be responsible for the development of fibrosis. Our group previously reported an association between subjects with PHFM and human leukocyte antigen (HLA)-A*02. We sought to confirm or extend those findings with application of high resolution HLA typing in a cohort of subjects with PHFM.

Methods
High-resolution HLA typing was performed on DNA samples from a new cohort 34 patients with PHFM. Control cohorts included 707 subjects from the “European American” subset of the National Marrow Donor Program® (NMDP) and 700 subjects from Dialysis Clinic, Inc. (DCI). The carriage frequencies of the HLA alleles identified in the PHFM, NMDP, and DCI cohorts were calculated and then all were compared.

Results
We found an increase in the carriage frequency of HLA-DQB1*04:02 in PHFM subjects relative to the controls (0.15 versus 0.07 in DCI and 0.05 in NMDP; p = 0.08 and 0.03). Multiple logistic regression showed that DQB1*04:02 was statistically significant (p = 0.04), while DQB1*03:02 and C*03:04 had point estimates of OR > 1, though they did not reach statistical significance. The HLA-A*02 association was not replicated.

Conclusions
HLA-DQB1*04:02 is associated with PHFM, which supports the premise that an aberrant host immune response contributes to the development of PHFM.

Publication Type: Journal Article
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Publisher: BioMed Central
Copyright: © 2015 Strock et al.
URI: http://researchrepository.murdoch.edu.au/id/eprint/26736
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