Table 1.

Clinical correlations between died-induced A-GcAbs and pathologies.

Pathologies	Aim/rational	Clinical findings	Significance and limits	References
Malignancy	Investigate whether anti-Neu5Gc antibodies increase the risk of colorectal cancer (CRC).	No correlation was found between antibodies against Neu5Gc alone or against individual Neu5Gc-bearing epitopes and CRC. However, a sialoglycan microarray study demonstrated a positive association of CRC risk and total anti-Neu5Gc-glycan antibody responses.	Whilst a correlation of CRC with the total anti-Neu5Gc antibody response has been demonstrated, a link with causation is still lacking.High Neu5Gc loading of malignant cells may also boost anti-NeuGc levels.	(4)
	Investigate whether anti-Neu5Gc elicited by rabbit IgGs are associated with a higher incidence of colon carcinoma.	There was no evidence that exposure to high levels of elicited anti-Neu5Gc antibodies is associated with a higher incidence of colon carcinoma.	This study relies on indirect evidence: ATG-treated renal allograft recipients have high-level anti-Neu5Gc antibodies.	(28)
Vascular diseases	Investigate if the levels of A-GcAbs correlate with chronic vascular lesions.	No correlation of A-GcAbs with coronary artery disease (CAD).	Case-control study using three tests for A-GcAbs (835 CAD vs. 1869 controls).	(21)
	Investigate if the levels of A-GcAbs correlate with acute vascular lesions.	No acute vascular pathology reported in young type 1 diabetic patients with extremely high titers of elicited A-GcAbs.	Deals with elicited A-GcAbs.	(18, 27)
		Inverse correlation of A-GcAbs and arterial lesions in Kawasaki disease.	Case-control study.No reported vascular pathologies.	(29)
		Increase A-GcAbs in acute EBV primo infection (IMN).	No reported vascular lesion in IMN.	(30)
Infertility	A-GcAbs could block the capacitation and migration of Neu5Gc-loaded spermatozoid, and egg fecundation and implantation in the female uterine tract exhibiting Neu5Gc.	No correlation between the presence of Neu5Gc or A-GcAbs in uterine tract and semen quality or uterine pathology.	Only a minority of men, even from infertile couples, incorporated Neu5Gc in sperm.Interesting hypothesis but limited number of cases studied yet.	(31)
Asthma	Investigate whether exposure to Neu5Gc is involved in the protection against allergy, asthma, and inflammatory bowel disease observed in children exposed to farm environment.	Farmers' children had elevated levels of anti-Neu5Gc antibodies that were inversely correlated with wheezing and asthma in non-atopic subjects.	Significant limit: the authors speculate that Neu5Gc behaves in vitro as an anti-inflammatory molecule in humans. However, free circulating Neu5C is controversial in vivo.	(32)
Multiple sclerosis	Possible effect on Brain Blood Barrier permeability	A-GcAb reactivity towards some Neu5Gc-bearing synthetic glycans in MS patients.	No increase of A-GcAbs in the blood of MS patients in another study.	(30, 33)