Two chicken monoclonal antibodies specific for heterophil Hanganutziu-Deicher antigens

Asaoka, Hideyuki; Nishinaka, Shigeyuki; Wakamiya, Nobutaka; Matsuda, Haruo; Murata, Masayoshi

doi:10.1016/0165-2478(92)90205-3

Cited by 55 publications

(8 citation statements)

References 12 publications

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“…Indeed, chemo-enzymatically synthesized α2-3 or α2-6 linked sialoside pairs (i.e., identical glycans with either Neu5Gc or Neu5Ac) (78, 79) were used to analyze anti-Neu5Gc antibodies, revealing complex patterns of IgG, IgM, and IgA reactivities with marked variations in the antibody profiles within the normal human population (73). In retrospect, this also explains prior successes in obtaining monoclonal antibodies with specificities for particular Neu5Gc-containing molecules (74, 80–84). …”

Section: Origins and Implications Of The Human Immune Response Againsmentioning

confidence: 72%

“…The discrepancy with the earlier studies was likely due to the different methods of detection and/or antigens used in the assays. One of the cancer-associated H–D antigens used as the ELISA detection target in earlier studies was the ganglioside GM3(Neu5Gc) (4, 74, 75), an antigen against which antibodies in healthy humans tend to be low. Also, in some studies the antibody binding signal in normal subjects was simply assumed to be non-specific and subtracted as background (30, 76).…”

Section: Origins and Implications Of The Human Immune Response Againsmentioning

confidence: 99%

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Involvement of a Non-Human Sialic Acid in Human Cancer

et al. 2014

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Sialic acids are common monosaccharides that are widely expressed as outer terminal units on all vertebrate cell surfaces, and play fundamental roles in cell–cell and cell–microenvironment interactions. The predominant sialic acids on most mammalian cells are N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac). Neu5Gc is notable for its deficiency in humans due to a species-specific and species-universal inactivating deletion in the CMAH gene encoding the hydroxylase that converts CMP-Neu5Ac to CMP-Neu5Gc. However, Neu5Gc is metabolically incorporated into human tissues from dietary sources (particularly red meat), and detected at even higher levels in some human cancers. Early life exposure to Neu5Gc-containing foods in the presence of certain commensal bacteria that incorporate dietary Neu5Gc into lipooligosaccharides can lead to generation of antibodies that are also cross-reactive against Neu5Gc-containing glycans in human tissues (“xeno-autoantigens”). Such anti-Neu5Gc “xeno-autoantibodies” are found in all humans, although ranging widely in levels among individuals, and displaying diverse and variable specificities for the underlying glycan. Experimental evidence in a human-like Neu5Gc-deficient Cmah−/−mouse model shows that inflammation due to “xenosialitis” caused by this antigen–antibody interaction can promote tumor progression, suggesting a likely mechanism for the well-known epidemiological link between red meat consumption and carcinoma risk. In this review, we discuss the history of this field, mechanisms of Neu5Gc incorporation into tissues, the origin and specificities of human anti-Neu5Gc antibodies, their use as possible cancer biomarkers, implications of xenosialitis in cancer initiation and progression, and current and future approaches toward immunotherapy that could take advantage of this unusual human-specific phenomenon.

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Section: Origins and Implications Of The Human Immune Response Againsmentioning

confidence: 72%

Section: Origins and Implications Of The Human Immune Response Againsmentioning

confidence: 99%

Involvement of a Non-Human Sialic Acid in Human Cancer

et al. 2014

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“…Many years later, similar antibodies were also found in patients with autoimmune diseases, such as rheumatoid arthritis and Kawasaki disease and various types of cancer (Nishimaki et al, 1978a; Nishimaki et al, 1978b; Arita et al, 1982; Ikuta et al, 1982; Hokke et al, 1990; Gathuru et al, 1989; Higashihara et al, 1991). Subsequent studies then showed that these antibodies were directed against Neu5Gc and could target carcinoma antigens such as the monosialoganglioside (Neu5Gc)GM3 (Higashi et al, 1977; Asaoka et al, 1992; Malykh et al, 2001b). Because (Neu5Gc)GM3 was a well-known target for anti-Neu5Gc antibodies, it was used as capture antigen to detect anti-Neu5Gc antibodies in human individuals.…”

Section: Existing Theories To Explain Increased Disease Risks Of Rmentioning

confidence: 99%

Human risk of diseases associated with red meat intake: Analysis of current theories and proposed role for metabolic incorporation of a non-human sialic acid

Alisson-Silva

Kawanishi

Varki

2016

Molecular Aspects of Medicine

130

103

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One of the most consistent epidemiological associations between diet and human disease risk is the impact of red meat consumption (beef, pork, and lamb, particularly in processed forms). While risk estimates vary, associations are reported with all-cause mortality, colorectal and other carcinomas, atherosclerotic cardiovascular disease, type II diabetes, and possibly other inflammatory processes. There are many proposed explanations for these associations, some long discussed in the literature. Attempts to explain the effects of red meat consumption have invoked various red meat-associated agents, including saturated fat, high salt intake, Trimethylamine–N-oxide (TMAO) generation by microbiota, and environmental pollutants contaminating red meat, none of which are specific for red meat. Even the frequently mentioned polycyclic aromatic carcinogens arising from high temperature cooking methods are not red meat specific, as these are also generated by grilling poultry or fish, as well as by other forms of cooking. The traditional explanations that appear to be more red meat specific invoke the impact of N-nitroso compounds, heme iron, and the potential of heme to catalyze endogenous nitrosation. However, heme can be denatured by cooking, high levels of plasma hemopexin will block its tissue delivery, and much higher amounts of heme likely originate from red blood cell breakdown in vivo. Therefore, red meat-derived heme could only contribute to colorectal carcinoma risk, via direct local effects. Also, none of these mechanisms explain the apparent human propensity i.e., other carnivores have not been reported at high risk for all these diseases. A more recently proposed hypothesis involves infectious agents in beef from specific dairy cattle as agents of colorectal cancer. We have also described another mechanistic explanation for the human propensity for risk of red-meat associated diseases that is consistent with most observations: metabolic incorporation of a non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) into the tissues of red meat consumers and the subsequent interaction with inflammation-provoking antibodies against this “xenoautoantigen”. Overall, we conclude that while multiple mechanisms are likely operative, many proposed theories to date are not specific for red meat, and that the viral and xenoautoantigen theories deserve further consideration. Importantly, there are potential non-toxic dietary antidotes, if the xenoautoantigen is indeed correct.

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“…Chicken anti-NeuGc monoclonal IgG Abs (HU/Ch2-7; Pharma Foods International Co., Ltd., Kyoto, Japan) were used for the detection of NeuGc Ag in the hepatectomized liver tissues. 10,11 HU/Ch2-7, which reacted strongly with NeuGc Ag, was specifically directed toward an antigenic epitope containing NeuGc. 11 The sections were incubated with HU/Ch2-7 in phosphatebuffered saline (PBS) overnight.…”

Section: Immunohistochemistry Assaymentioning

confidence: 99%

Heterophile carbohydrate antigen N‐glycolylneuraminic acid as a potential biomarker in patients with hepatocellular carcinoma

et al. 2023

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Background and ObjectivesHepatocellular carcinoma (HCC) has a high recurrence rate even after radical hepatectomy. More optimal biomarkers may help improve recurrence and prognosis.MethodsWe investigated whether the oncological properties of N‐glycolylneuraminic acid (NeuGc) can participate in the prognosis of HCC. We evaluated the NeuGc antigen (Ag) expression in the HCC tissues and measured the preoperative anti‐NeuGc IgG antibodies (Abs) in the sera of the patients with HCC. We compared the clinical characteristics and survival rate in the hepatectomized patients (initial; n = 66, recurrent; n = 34) with and without the NeuGc Ag or Abs.ResultsMultivariate analyses showed positive expression of NeuGc Ag in HCC tissues (Odds ratio; initial = 6.3, recurrent = 14.0) and higher titers of preoperative anti‐NeuGc Ab (Odds ratio; initial = 4.9; recurrent = 3.8), which could be the predictive factors related to early recurrence. Both the NeuGc Ag‐positive and Ab‐positive groups in the initial hepatectomized patients exhibited significantly shorter recurrent free survival compared to those in the negative groups.ConclusionsOur findings suggested that anti‐NeuGc Ab titers and NeuGc Ag expression in the HCC tissues can be used as the predictive factors for the postoperative recurrence and prognosis of HCC.

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Two chicken monoclonal antibodies specific for heterophil Hanganutziu-Deicher antigens

Cited by 55 publications

References 12 publications

Involvement of a Non-Human Sialic Acid in Human Cancer

Involvement of a Non-Human Sialic Acid in Human Cancer

Human risk of diseases associated with red meat intake: Analysis of current theories and proposed role for metabolic incorporation of a non-human sialic acid

Heterophile carbohydrate antigen N‐glycolylneuraminic acid as a potential biomarker in patients with hepatocellular carcinoma

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