Abstract | BACKGROUND: METHODS: ELISA assays measured antibodies against Neu5Gc or Neu5Gc-glycans in plasma or serum samples from the Nurses' Health Studies, the Health Professionals Follow-up Study, and the European Prospective Investigation into Cancer and Nutrition, including inter-assay reproducibility, stability with delayed sample processing, and within-person reproducibility over 1-3 years in archived samples. We also assessed associations between antibody levels and coronary artery disease risk (CAD) or red meat intake. A glycan microarray was used to detected antibodies against multiple Neu5Gc-glycan epitopes. A nested case-control study design assessed the association between total anti-Neu5Gc antibodies detected in the glycan array assay and the risk of colorectal cancer (CRC). RESULTS: ELISA assays showed a wide range of anti-Neu5Gc responses and good inter-assay reproducibility, stability with delayed sample processing, and within-person reproducibility over time, but these antibody levels did not correlate with CAD risk or red meat intake. Antibodies against Neu5Gc alone or against individual Neu5Gc-bearing epitopes were also not associated with colorectal cancer (CRC) risk. However, a sialoglycan microarray study demonstrated positive association with CRC risk when the total antibody responses against all Neu5Gc-glycans were combined. Individuals in the top quartile of total anti-Neu5Gc IgG antibody concentrations had nearly three times the risk compared to those in the bottom quartile (Multivariate Odds Ratio comparing top to bottom quartile: 2.98, 95% CI: 0.80, 11.1; P for trend = 0.02). CONCLUSIONS: Further work harnessing the utility of these anti-Neu5Gc antibodies as biomarkers in red meat-associated diseases must consider diversity in individual antibody profiles against different Neu5Gc-bearing glycans. Traditional ELISA assays for antibodies directed against Neu5Gc alone, or against specific Neu5Gc-glycans may not be adequate to define risk associations. Our finding of a positive association of total anti-Neu5Gc antibodies with CRC risk also warrants confirmation in larger prospective studies.
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Authors | Annie N Samraj, Kimberly A Bertrand, Robert Luben, Zahra Khedri, Hai Yu, Dzung Nguyen, Christopher J Gregg, Sandra L Diaz, Sherilyn Sawyer, Xi Chen, Heather Eliassen, Vered Padler-Karavani, Kana Wu, Kay-Tee Khaw, Walter Willett, Ajit Varki |
Journal | PloS one
(PLoS One)
Vol. 13
Issue 6
Pg. e0197464
( 2018)
ISSN: 1932-6203 [Electronic] United States |
PMID | 29912879
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- Autoantigens
- Epitopes
- Neuraminic Acids
- Polysaccharides
- N-glycolylneuraminic acid
- N-Acetylneuraminic Acid
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Topics |
- Adult
- Aged
- Antibodies
(immunology)
- Atherosclerosis
(blood, immunology, pathology)
- Autoantigens
(immunology)
- Colorectal Neoplasms
(blood, epidemiology, immunology)
- Diabetes Mellitus, Type 2
(blood, epidemiology, immunology)
- Epitopes
(immunology)
- Female
- Humans
- Middle Aged
- N-Acetylneuraminic Acid
(immunology)
- Neuraminic Acids
(immunology, isolation & purification)
- Polysaccharides
(immunology, isolation & purification)
- Red Meat
(adverse effects)
- Risk Factors
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