@article{1bf8be4f930c48e4a4e1d186b6223985,
title = "Increasing Levels of Serum Heat Shock Protein 70 Precede the Development of AIDS-Defining Non-Hodgkin Lymphoma among Carriers of HLA-B8-DR3",
abstract = "Background:We hypothesized that carriage of presumably high Hsp70-producing gene variants on a specific human major histocompatibility complex haplotype, the 8.1 ancestral haplotype (8.1AH), may predispose HIV-infected individuals to AIDS-non-Hodgkin lymphoma (NHL).Setting:We compared serum Hsp70 levels in the years preceding the diagnosis of AIDS-NHL in a matched case-control study (n = 151 pairs) nested in the Multicenter AIDS Cohort Study.Methods:We tested the impact of 8.1AH-specific single-nucleotide polymorphism (SNP) and joint SNP-human leukocyte antigen extended haplotypes previously associated with AIDS-NHL in the Multicenter AIDS Cohort Study on the circulating Hsp70 levels in mixed linear models.Results:We report elevated serum levels of Hsp70 in the 4 years preceding the diagnosis of AIDS-NHL in cases that carry 8.1AH, but not in noncarrier cases and not in carrier- or non-carrier-matched controls. The strongest predictor of higher serum Hsp70 was the haplotype A-G-A-C formed by SNPs rs537160(A) and rs1270942(G) in the complement factor CFB gene cluster, and rs2072633(A) and rs6467(C) in nearby RDBP and CYP21A2 located 70 Kb apart from the Hsp70 gene cluster. The association with A-G-A-C haplotype (beta = 0.718; standard error = 0.182; P = 0.0002) and with other 8.1AH-specific haplotypes including the high-producing tumor necrosis factor-alpha haplotype rs909253(G)-rs1800629(A) (beta = 0.308; standard error = 0.140; P = 0.032) were observed only with NHL identified as an AIDS-defining condition, but not as a post-AIDS condition, nor in combined AIDS and post-AIDS cases.Conclusion:Our combined genetic and functional approach suggests that the altered level of Hsp70 is a correlate of 8.1AH-mediated AIDS-NHL. Further investigation of the Hsp70 gene cluster and nearby loci that are tagged by A-G-A-C could better elucidate the genetic determinants of the malignancy.",
keywords = "8.1AH, AIDS, HIV, HLA-B8, Hsp70, MHC haplotypes, lymphoma",
author = "Brahim Aissani and Otoniel Martinez-Maza and Kaslow, {Richard A.} and Wiener, {Howard W.} and Bream, {Jay H.} and Valentina Stosor and Martinson, {Jeremy J.} and Jacobson, {Lisa P.} and Sadeep Shrestha",
note = "Funding Information: Supported by subcontract (B.A.) to NIH/NCI P30-AI045008 (PI: Hoxie). Funding Information: Data in this article were collected by the MACS. MACS (Principal Investigators): Johns Hopkins University Bloom-berg School of Public Health (Joseph Margolick), U01-AI35042; Northwestern University (Steven Wolinsky), U01-AI35039; University of California, Los Angeles (Roger Detels), U01-AI35040; University of Pittsburgh (Charles Rinaldo), U01-AI35041; the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson), UM1-AI35043. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the National Cancer Institute (NCI). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI), and the National institute of Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR000424 (JHU CTSA). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NHI). Website located at http://www.statepi.jhsph.edu/macs/macs. html. Funding Information: Supported by subcontract (B.A.) to NIH/NCI P30-AI045008 (PI: Hoxie). The Multicenter AIDS Cohort Study (MACS) is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute and the National Heart, Lung, and Blood Institute. UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, and UO1-AI-35041. This work was also supported by the Pendleton Charitable Trust and the McCarthy Family Foundation (OMM), and by the Quetelet Endowed Professor Research Fund (SS). Publisher Copyright: {\textcopyright} 2019 The Author(s). Published by Wolters Kluwer Health, Inc.",
year = "2019",
month = jul,
day = "1",
doi = "10.1097/QAI.0000000000002027",
language = "English (US)",
volume = "81",
pages = "266--273",
journal = "Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "3",
}