Biomedical Differences Between Human and Nonhuman Hominids: Potential Roles for Uniquely Human Aspects of Sialic Acid Biology

Abstract

Although humans are genetically very similar to the evolutionarily related nonhuman hominids (chimpanzees, bonobos, gorillas, and orangutans), comparative studies suggest a surprising number of uniquely human differences in the incidence and/or severity of biomedical conditions. Some differences are due to anatomical changes that occurred during human evolution. However, many cannot be explained either by these changes or by known environmental factors. Because chimpanzees were long considered models for human disease, it is important to be aware of these differences, which appear to have been deemphasized relative to similarities. We focus on the pathophysiology and pathobiology of biomedical conditions that appear unique to humans, including several speculative possibilities that require further study. We pay particular attention to the possible contributions of uniquely human changes in the biology of cell-surface sialic acids and the proteins that recognize them. We also discuss the metabolic incorporation of a diet-derived nonhuman sialic acid, which generates a novel xeno-autoantigen reaction, and chronic inflammation known as xenosialitis.

Detection of the dietary xenoglycan N-glycolylneuraminic acid (Neu5Gc) and anti-Neu5Gc antibodies within reproductive tracts of male and female infertility subjects

“…Such investigations will reveal to what extent xenosialitis, the contribution of the xenoglycan Neu5Gc to heightened or chronic inflammation, also affects human reproduction [18]and will point to potential mechanisms involved.…”

“…More sensitive detection methods have provided evidence for widespread anti-Neu5Gc antibodies in most humans tested, including IgM, IgA, and IgG antibodies [17]. There is mounting evidence that the dietary bioaccumulation of xenoglycan and production of targeting antibodies might underlie various forms of xenosialitis [18].…”

Metabolism of Vertebrate Amino Sugars with N-Glycolyl Groups

“…In striking contrast, the human immune system regards Neu5Gc-containing glycan structures as "foreign," resulting in a polyclonal humoral response, with circulating and varying titers of anti-Neu5Gc antibodies among all humans (29,30). The incorporation of dietary Neu5Gc in the face of an ongoing immune response against this non-human epitope makes Neu5Gc the first known example of a "xeno-autoantigen" (31,32). Interestingly, the major sites of Neu5Gc accumulation in humans (endothelia of blood vessels and epithelia lining the hollow organs) are also the locations where predominantly human-specific diseases involving chronic inflammation seem to occur (31).…”

“…The incorporation of dietary Neu5Gc in the face of an ongoing immune response against this non-human epitope makes Neu5Gc the first known example of a "xeno-autoantigen" (31,32). Interestingly, the major sites of Neu5Gc accumulation in humans (endothelia of blood vessels and epithelia lining the hollow organs) are also the locations where predominantly human-specific diseases involving chronic inflammation seem to occur (31). Notably, such chronic inflammationmediated human health issues (e.g.…”

“…However, in the face of the described Neu5Gc-degrading pathway, simple switching to a Neu5Gc-free diet should likely eliminate already accumulated Neu5Gc from the human body over time. Thus, adjusting the diet may further support current treatment of diseases involving chronic inflammation, which may be aggravated by xenosialitis (reaction of human anti-Neu5Gc antibodies with the non-human xeno-autoantigen Neu5Gc being expressed) (31). An alternative approach involves eliminating Neu5Gc by metabolic competition with Neu5Ac (87).…”