Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic acid <i>N</i>-glycolylneuraminic acid

Taylor, Rachel E.; Gregg, Christopher; Padler‐Karavani, Vered; Ghaderi, Darius; Yu, Hai; Huang, Shengshu; Sorensen, Ricardo U.; Chen, Xi; Inostroza, Jaime; Nizet, Victor; Varki, Ajit

doi:10.1084/jem.20100575

Cited by 139 publications

(161 citation statements)

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“…Unlike adult humans, Cmah(−/−) mice do not have circulating antibodies against Neu5Gc (19). However, they can be immunized against Neu5Gc using a mechanism similar to that which induces human anti-Neu5Gc antibodies: incorporation of Neu5Gc into the lipo-oligosaccharides of the human-specific commensal microbe Haemophilus influenzae (17). As with humans, immunization with this Neu5Gc-expressing bacterium generates an antiNeu5Gc response that varies among individual Cmah(−/−) mice.…”

Section: Resultsmentioning

confidence: 99%

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Sexual selection by female immunity against paternal antigens can fix loss of function alleles

Ghaderi

Springer

et al. 2011

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

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Humans lack the common mammalian cell surface molecule N-glycolylneuraminic acid (Neu5Gc) due to a CMAH gene inactivation, which occurred approximately three million years ago. Modern humans produce antibodies specific for Neu5Gc. We hypothesized that anti-Neu5Gc antibodies could enter the female reproductive tract and target Neu5Gc-positive sperm or fetal tissues, reducing reproductive compatibility. Indeed, female mice with a human-like Cmah(−/−) mutation and immunized to express anti-Neu5Gc antibodies show lower fertility with Neu5Gc-positive males, due to prezygotic incompatibilities. Human anti-Neu5Gc antibodies are also capable of targeting paternally derived antigens and mediate cytotoxicity against Neu5Gc-bearing chimpanzee sperm in vitro. Models of populations polymorphic for such antigens show that reproductive incompatibility by female immunity can drive loss-offunction alleles to fixation from moderate initial frequencies. Initially, the loss of a cell-surface antigen can occur due to drift in isolated populations or when natural selection favors the loss of a receptor exploited by pathogens, subsequently the same loss-offunction allele can come under sexual selection because it avoids being targeted by the female immune system. Thus, we provide evidence of a link between sexual selection and immune function: Antigenicity in females can select against foreign paternal antigens on sperm and rapidly fix loss-of-function alleles. Similar circumstances existed when the CMAH null allele was polymorphic in ancestral hominins, just before the divergence of Homo from australopithecines.glycan antigen | sialic acid | xeno-antigens

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Section: Resultsmentioning

confidence: 99%

“…1). Human antibody profiles against Neu5Gc are varied in level and composition, but all humans have circulating antibodies against Neu5Gc, which appear early in life (15)(16)(17). The antibody repertoire of females also extends to their reproductive tract, through which the sperm must pass and in which embryos must implant (18).…”

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confidence: 99%

Sexual selection by female immunity against paternal antigens can fix loss of function alleles

Ghaderi

Springer

et al. 2011

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

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“…However, besides α-Gal, a sialic acid named Neu5Gc is the only mammalian carbohydrate present in high amounts in beef, lamb, pork, and cow's milk [36]. Similar to α-Gal, Neu5Gc is found in most mammals including primates [37] but not in humans due to a mutation in the gene encoding the enzyme responsible for Neu5Gc synthesis.…”

Section: Features Of the Immune Response To Carbohydratesmentioning

confidence: 99%

The red meat allergy syndrome in Sweden

Apostolović¹,

Tran²,

Starkhammar³

et al. 2016

Allergo J

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SummaryIn the last decade, a novel type of food allergy presenting with severe allergic reactions several hours a er consumption of red meat has been recognized.e allergic responses are due to IgE antibodies directed against the carbohydrate epitope galactose-α-1,3-galactose (α-Gal) found in mammalian meat.is review presents the red meat allergy syndrome in Sweden, discusses the features of the immune response to carbohydrates, and highlights the presence of heat stable α-Gal-containing proteins in meat.e number of diagnosed red meat allergy cases in Sweden has increased signi cantly over the past few years. All patients have been tick bitten. Our recent work has shown that α-Gal is present in the Euro pean tick Ixodes ricinus (I. ricinus), thus potentially explaining the strong association between anti-α-Gal IgE and tick bites, with development of red meat allergy as a secondary phenomenon. Further studies using immunoproteomics have identi ed novel α-Gal-containing meat proteins that bound IgE from red meat allergic patients. Four of these proteins were stable to thermal processing pointing to the fact that the allergenicity of red meat proteins is preserved in cooked meat. In keeping with the fact that the α-Gal epitope is structurally related to the blood group B antigen, a positive association with the B-negative blood groups among our red meat allergic patients was noted. A selective IgE reactivity to the pure carbohydrate moiety was observed when investigating the speci city of the α-Gal immune response. IgE from red meat allergic patients does not recognize the other major mammalian carbohydrate, N-glycolylneuraminic acid (Neu5Gc), also present in high amounts in red meat. Furthermore, neither common cross-reactive carbohydrate determinants (CCDs) from plants nor venoms are targets of the IgE response in these patients.Taken together, the α-Gal carbohydrate has shown to be a potentially clinically relevant allergen that should be taken into account in the diagnosis of food allergy. Many new ndings in the eld of red meat allergy have been obtained during the past years, but further e orts to understand the process of digestion, absorption, and delivery of α-Gal-containing molecules to the circulation are needed. e red meat allergy syndrome in Sweden. Allergo Cite this as

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“…Intriguingly, the steep increase of MS prevalence in Japan after World War II has been attributed to the replacement of the Neu5GC-poor traditional Japanese food by the Neu5GC-rich Western diet (Yamamura and Miyake, 2013). Experiments in CMAHdeficient mice have shown that dietary Neu5Gc is incorporated in the gut flora and in the glycocalyx of various body tissues (Taylor et al, 2010). The dietary modified gut flora induces the production of heterophilic antibodies, which can bind Neu5Gc incorporated in tissue glycocalyx and in this way interfere with cellular interactions and communication (Taylor et al, 2010;Samraj et al, 2014).…”

Section: Modeling the Cause Of The Primary Lesionmentioning

confidence: 99%

“…Experiments in CMAHdeficient mice have shown that dietary Neu5Gc is incorporated in the gut flora and in the glycocalyx of various body tissues (Taylor et al, 2010). The dietary modified gut flora induces the production of heterophilic antibodies, which can bind Neu5Gc incorporated in tissue glycocalyx and in this way interfere with cellular interactions and communication (Taylor et al, 2010;Samraj et al, 2014).…”

Section: Modeling the Cause Of The Primary Lesionmentioning

confidence: 99%

The common marmoset (<i>Callithrix jacchus</i>): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain

et al. 2016

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Abstract. The increasing prevalence of chronic autoimmune-mediated inflammatory disorders (AIMIDs) in aging human populations creates a high unmet need for safe and effective medications. However, thus far the translation of pathogenic concepts developed in animal models into effective treatments for the patient has been notoriously difficult. The main reason is that currently used mouse-based animal models for the pipeline selection of promising new treatments were insufficiently predictive for clinical success. Regarding the high immunological similarity between human and non-human primates (NHPs), AIMID models in NHPs can help to bridge the translational gap between rodent and man. Here we will review the preclinical relevance of the experimental autoimmune encephalomyelitis (EAE) model in common marmosets (Callithrix jacchus), a small-bodied neotropical primate. EAE is a generic AIMID model projected on the human autoimmune neuro-inflammatory disease multiple sclerosis (MS).

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Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic acid N-glycolylneuraminic acid

Cited by 139 publications

References 60 publications

Sexual selection by female immunity against paternal antigens can fix loss of function alleles

Sexual selection by female immunity against paternal antigens can fix loss of function alleles

The red meat allergy syndrome in Sweden

The common marmoset (<i>Callithrix jacchus</i>): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain

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Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic acid N-glycolylneuraminic acid

Cited by 139 publications

References 60 publications

Sexual selection by female immunity against paternal antigens can fix loss of function alleles

Sexual selection by female immunity against paternal antigens can fix loss of function alleles

The red meat allergy syndrome in Sweden

The common marmoset (&lt;i&gt;Callithrix jacchus&lt;/i&gt;): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain

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The common marmoset (<i>Callithrix jacchus</i>): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain