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Hum Immunol. 2018 Aug;79(8):632-637. doi: 10.1016/j.humimm.2018.06.001. Epub 2018 Jun 4.

IGHG, IGKC, and FCGR genes and endogenous antibody responses to GARP in patients with breast cancer and matched controls.

Author information

1
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, United States. Electronic address: pandeyj@musc.edu.
2
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, United States.
3
Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, United States.
4
Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
5
Department of Surgery, Nagano Matsushiro General Hospital, Nagano, Japan.
6
Nikkei Disease Prevention Center, São Paulo, Brazil.
7
Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Abstract

Glycoprotein-A repetitions predominant (GARP) is a transmembrane protein that is highly expressed in breast cancer. Its overexpression correlates with worse survival, and antibodies to GARP appear to play a protective role in a mouse model. No large-scale studies of immunity to GARP in humans have yet been undertaken. In this investigation, using a large multiethnic cohort (1738 subjects), we aimed to determine whether the magnitude of anti-GARP antibody responsiveness was significantly different in patients with breast cancer from that in matched healthy controls. We also investigated whether the allelic variation at the immunoglobulin GM (γ marker), KM (κ marker), and Fcγ receptor (FcγR) loci contributed to the interindividual variability in anti-GARP IgG antibody levels. A combined analysis of all subjects showed that levels of anti-GARP antibodies were significantly higher in patients with breast cancer than in healthy controls (mean ± SD: 7.4 ± 3.5 vs. 6.9 ± 3.5 absorbance units per mL (AU/μL), p < 0.0001). In the two populations with the largest sample size, the probability of breast cancer generally increases as anti-GARP antibody levels increase. Several significant individual and epistatic effects of GM, KM, and FcγR genotypes on anti-GARP antibody responsiveness were noted in both patients and controls. These results, if confirmed by independent investigations, will aid in devising personalized GARP-based immunotherapeutic strategies against breast cancer and other GARP-overexpressing malignancies.

KEYWORDS:

FcγR genes; GARP; GM/KM allotypes; Humoral immunity

PMID:
29879453
PMCID:
PMC6063529
[Available on 2019-08-01]
DOI:
10.1016/j.humimm.2018.06.001
[Indexed for MEDLINE]

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