Fibrosing mediastinitis complicating prior histoplasmosis is associated with human leukocyte antigen DQB1*04:02 - a case control study.
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.
Department of Medicine, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. stephen.b.strock@vanderbilt.edu.
Stephen B
SB
Strock
School of Anatomy, Physiology and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia. silvana.gaudieri@uwa.edu.au.|Institute for Immunology & Infectious Disease, Murdoch University, Health Research Centre, Discovery Way, Murdoch, WA, 6150, Australia. silvana.gaudieri@uwa.edu.au.
Silvana
S
Gaudieri
Institute for Immunology & Infectious Disease, Murdoch University, Health Research Centre, Discovery Way, Murdoch, WA, 6150, Australia. s.mallal@vanderbilt.edu.|Department of Infectious Disease and Pathology, Microbiology and Immunology, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. s.mallal@vanderbilt.edu.
Simon
S
Mallal
Department of Biostatistics, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. chang.yu@vanderbilt.edu.
Chang
C
Yu
Pulmonary and Critical Care Medicine, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. daphne.mitchell@vanderbilt.edu.
Daphne
D
Mitchell
Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. joy.cogan@vanderbilt.edu.
Joy
J
Cogan
Pulmonary and Critical Care Medicine, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. wendi.mason@vanderbilt.edu.
Wendi
W
Mason
DCI Laboratory - Transplant Immunology, 1616 Hayes St, Nashville, TN, 37203, USA. deborah.crowe@dciinc.org.
Deborah
D
Crowe
Pulmonary and Critical Care Medicine, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. jim.loyd@vanderbilt.edu.
James E
JE
Loyd
D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D059866:HLA-DQ beta-Chains / Q000235:genetics* / Q000276:immunology; D006658:Histoplasma; D006660:Histoplasmosis / Q000150:complications / Q000276:immunology*; D006801:Humans; D008297:Male; D008480:Mediastinitis / Q000150:complications / Q000276:immunology*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012598:Sclerosis / Q000150:complications / Q000276:immunology*; D013714:Tennessee
D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen