Survey of Hanganutziu and Deicher Antibodies in Operated Patients

Higashihara, Tomoko; Takeshima, Toshio; Anzai, Mitsuaki; Tomioka, Minetoshi; Matsumoto, Kaoru; Nishida, Kazuhiro; Kitamura, Yoshihisa; Okinaga, Kota; Naiki, Masaharu

doi:10.1159/000235434

Cited by 27 publications

(22 citation statements)

References 7 publications

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“…While this article was in preparation, another group independently reported a high prevalence of anti-Neu5Gc antibodies in normal human sera, using a different approach (39). The findings of both studies stand in contrast to previous reports of the prevalence of anti-Neu5Gc antibodies in normal humans, ranging only from 0-10% for the IgG class to 3.8-13.8% for the IgM class (40)(41)(42). This disparity can be explained by the greater sensitivity and lower background of the assays we used, the use of an optimal control target (identical except for Neu5Ac in place of Neu5Gc), and the checks for specificity (blockade by chimpanzee but not human serum, or by free Neu5Gc but not free Neu5Ac).…”

Section: Discussionmentioning

confidence: 64%

“…Some other diseases such as hepatitis, liver cirrhosis, infectious mononucleosis, rheumatoid arthritis, syphilis, and lepromatous leprosy are claimed to be associated with ''Hanganutziu-Deicher'' heterophile anti-Neu5Gc antibodies (40)(41)(42). Such antibodies could play a role in initiation or progression or simply arise from immune dysregulation that allows preexisting memory B cells to expand.…”

Section: Discussionmentioning

confidence: 99%

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Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid

Tangvoranuntakul

Gagneux

Díaz

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

551

586

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Humans are genetically unable to produce the sialic acid N-glycolylneuraminic acid (Neu5Gc), because of a mutation that occurred after our last common ancestor with great apes. Although Neu5Gc is presumed absent from normal humans, small amounts have been claimed to exist in human tumors and fetal meconium. We have generated an antibody with high specificity and avidity for Neu5Gc. Fetal tissues, normal adult tissues, and breast carcinomas from humans showed reactivity to this antibody, primarily within secretory epithelia and blood vessels. The presence of small amounts of Neu5Gc was confirmed by MS. Absent any known alternate pathway for its synthesis, we reasoned that these small amounts of Neu5Gc might originate from exogenous sources. Indeed, human cells fed with Neu5Gc incorporated it into endogenous glycoproteins. When normal human volunteers ingested Neu5Gc, a portion was absorbed and eliminated in urine, and small quantities were incorporated into newly synthesized glycoproteins. Neu5Gc has never been reported in plants or microbes to our knowledge. We found that Neu5Gc is rare in poultry and fish, common in milk products, and enriched in red meats. Furthermore, normal humans have variable amounts of circulating IgA, IgM, and IgG antibodies against Neu5Gc, with the highest levels comparable to those of the previously known anti-␣-galactose xenoreactive antibodies. This finding represents an instance wherein humans absorb and metabolically incorporate a nonhuman dietary component enriched in foods of mammalian origin, even while generating xenoreactive, and potentially autoreactive, antibodies against the same molecule. Potential implications for human diseases are briefly discussed.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid

Tangvoranuntakul

Gagneux

Díaz

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

551

586

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“…These sugar nucleotides are the high energy donors necessary for the addition of sialic acid to glycoconjugates in the Golgi apparatus. Neu5Gc is found in large amounts in all mammals except humans, in whom it is even antigenic (21)(22)(23). Humans are evolutionarily most closely related to the African great apes, sharing nearly 99% genetic identity with Pan troglodytes (the chimpanzee) and Pan paniscus (the bonobo) and a somewhat lesser identity with Gorilla gorilla (the gorilla) and Pongo pygmaeus (the orangutan) (24 -30).…”

mentioning

confidence: 99%

Loss of N-Glycolylneuraminic Acid in Human Evolution

Linden¹,

Sjoberg²,

Juneja³

et al. 2000

Journal of Biological Chemistry

147

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The common sialic acids of mammalian cells are Nacetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). Humans are an exception, because of a mutation in CMP-sialic acid hydroxylase, which occurred after our common ancestor with great apes. We asked if the resulting loss of Neu5Gc and increase in Neu5Ac in humans alters the biology of the siglecs, which are Ig superfamily members that recognize sialic acids. Human siglec-1 (sialoadhesin) strongly prefers Neu5Ac over Neu5Gc. Thus, humans have a higher density of siglec-1 ligands than great apes. Siglec-1-positive macrophages in humans are found primarily in the perifollicular zone, whereas in chimpanzees they also occur in the marginal zone and surrounding the periarteriolar lymphocyte sheaths. Although only a subset of chimpanzee macrophages express siglec-1, most human macrophages are positive. A known evolutionary difference is the strong preference of mouse siglec-2 (CD22) for Neu5Gc, contrasting with human siglec-2, which binds Neu5Ac equally well. To ask when the preference for Neu5Gc was adjusted in the human lineage, we cloned the first three extracellular domains of siglec-2 from all of the great apes and examined their preference. In fact, siglec-2 had evolved a higher degree of recognition flexibility before Neu5Gc was lost in humans. Human siglec-3 (CD33) and siglec-6 (obesity-binding protein 1) also recognize both Neu5Ac and Neu5Gc, and siglec-5 may have some preference for Neu5Gc. Others showed that siglec-4a (myelin-associated glycoprotein) prefers Neu5Ac over Neu5Gc. Thus, the human loss of Neu5Gc may alter biological processes involving siglec-1, and possibly, siglec-4a or -5.

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“…They are called Hanganutziu and Deicher (HD) antigens. Cancer patients occasionally generate high-titre antibodies against HD antigens [9][10][11]. Chickens with Marek's disease lymphoma also express Neu5Gc [12] and the fact that chickens lack Neu5Gc was confirmed by the production of high-titre antibody in chickens immunized with Neu5Gc-containing gangliosides [13].…”

Section: Introductionmentioning

confidence: 99%

Evidence for a free N-acetylneuraminic acid-hydroxylating enzyme in pig mandibular gland soluble fraction

Mukuria

Mwangi

Waiyaki

et al. 1995

Biochemical Journal

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The activity of a free N-acetylneuraminic acid (Neu5Ac)-hydroxylating enzyme which converted Neu5Ac into N-glycolyl-neuraminic acid (Neu5Gc) was demonstrated in the soluble fraction of pig mandibular gland. The hydroxylation was possible only with NADPH as the electron donor. The apparent Km was 4.5 mM Neu5Ac. At 0.5 mM monovalent cations had no effect on the hydroxylation of Neu5Ac whereas bivalent cations gave varied inhibition capacities ranging from 14 to 75%. EDTA gave a time-dependent enhancement of activity. It was concluded that the enzyme does not require an exogenously added inorganic cofactor. Results from salt fractionation of the soluble fraction and the use of inhibitors such as mercurials suggested that the hydroxylation of Neu5Ac to Neu5Gc may involve other, as yet unknown, component(s) and the possibility of electrons donated by NADPH being transferred to activated molecular oxygen (second substrate). We propose to name this enzyme N-acetyl-neuraminic acid hydroxylase.

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Survey of Hanganutziu and Deicher Antibodies in Operated Patients

Cited by 27 publications

References 7 publications

Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid

Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid

Loss of N-Glycolylneuraminic Acid in Human Evolution

Evidence for a free N-acetylneuraminic acid-hydroxylating enzyme in pig mandibular gland soluble fraction

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