PMID- 25940591 OWN - NLM STAT- MEDLINE DCOM- 20151209 LR - 20201209 IS - 1471-2334 (Electronic) IS - 1471-2334 (Linking) VI - 15 DP - 2015 May 5 TI - Fibrosing mediastinitis complicating prior histoplasmosis is associated with human leukocyte antigen DQB1*04:02 - a case control study. PG - 206 LID - 10.1186/s12879-015-0943-7 [doi] LID - 206 AB - 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((R)) (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. FAU - Strock, Stephen B AU - Strock SB AD - Department of Medicine, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. stephen.b.strock@vanderbilt.edu. FAU - Gaudieri, Silvana AU - Gaudieri S AD - School of Anatomy, Physiology and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia. silvana.gaudieri@uwa.edu.au. AD - Institute for Immunology & Infectious Disease, Murdoch University, Health Research Centre, Discovery Way, Murdoch, WA, 6150, Australia. silvana.gaudieri@uwa.edu.au. FAU - Mallal, Simon AU - Mallal S AD - Institute for Immunology & Infectious Disease, Murdoch University, Health Research Centre, Discovery Way, Murdoch, WA, 6150, Australia. s.mallal@vanderbilt.edu. AD - Department of Infectious Disease and Pathology, Microbiology and Immunology, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. s.mallal@vanderbilt.edu. FAU - Yu, Chang AU - Yu C AD - Department of Biostatistics, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. chang.yu@vanderbilt.edu. FAU - Mitchell, Daphne AU - Mitchell D AD - Pulmonary and Critical Care Medicine, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. daphne.mitchell@vanderbilt.edu. FAU - Cogan, Joy AU - Cogan J AD - Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. joy.cogan@vanderbilt.edu. FAU - Mason, Wendi AU - Mason W AD - Pulmonary and Critical Care Medicine, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. wendi.mason@vanderbilt.edu. FAU - Crowe, Deborah AU - Crowe D AD - DCI Laboratory - Transplant Immunology, 1616 Hayes St, Nashville, TN, 37203, USA. deborah.crowe@dciinc.org. FAU - Loyd, James E AU - Loyd JE AD - Pulmonary and Critical Care Medicine, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN, 37232, USA. jim.loyd@vanderbilt.edu. LA - eng GR - UL1 RR024975/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150505 PL - England TA - BMC Infect Dis JT - BMC infectious diseases JID - 100968551 RN - 0 (HLA-DQ beta-Chains) RN - 0 (HLA-DQB1 antigen) RN - Mediastinal Fibrosis SB - IM MH - Adult MH - Case-Control Studies MH - Cohort Studies MH - Female MH - Gene Frequency MH - HLA-DQ beta-Chains/*genetics/immunology MH - *Histoplasma MH - Histoplasmosis/complications/*immunology MH - Humans MH - Male MH - Mediastinitis/complications/*immunology MH - Polymerase Chain Reaction MH - Prevalence MH - Sclerosis/complications/*immunology MH - Tennessee PMC - PMC4424560 EDAT- 2015/05/06 06:00 MHDA- 2015/12/15 06:00 PMCR- 2015/05/05 CRDT- 2015/05/06 06:00 PHST- 2015/01/08 00:00 [received] PHST- 2015/04/27 00:00 [accepted] PHST- 2015/05/06 06:00 [entrez] PHST- 2015/05/06 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] PHST- 2015/05/05 00:00 [pmc-release] AID - 10.1186/s12879-015-0943-7 [pii] AID - 943 [pii] AID - 10.1186/s12879-015-0943-7 [doi] PST - epublish SO - BMC Infect Dis. 2015 May 5;15:206. doi: 10.1186/s12879-015-0943-7.