Already by 6 months of age, gut microbiota polysaccharides stimulate antibodies capable of binding ABO blood group antigens (1). In particular, anti-histo blood group B antibodies can bind gut microbiota () while the environmental trigger for anti-histo blood group A still remains undefined ( ).
Thus, rather than indicative of defense,as in structural similarity between microbial and histo-blood group antigens explains antibodies against the latter. The 20th century human invention of blood transfusion simply uncovers the scope of such cross-reactivity (4).
A dynamic snapshot of a person’s immunological history, circulating antibodies embody the immunological imprint of past antigenic encounters. However, which antigens specifically induce such circulating antibodies? Grouped under the umbrella term,, they’re found in circulation even in absence of explicit infection. In actuality, the term simply signifies unknown antigenic targets triggered such antibodies. Until recently, explicitly looking for such antigens was akin to looking for the proverbial needle in a haystack.
Now thoughapproaches that combine high-throughput computational and techniques are beginning to trace out the broad overlaps in structure within the universe of antigens, overlaps that antibodies and other receptors of the already so brilliantly glom onto when they bind their antigenic targets so specifically.
Such studies reveal how a contradiction of terms, specificity married to redundancy, could even come to be such a hallmark feature of the adaptive immune system receptors. For example, one study () suggests a universal architecture for the human anti-carbohydrate antibody repertoire, universal implying capacity to bind structurally similar across living organisms, be they microbes or mammals.
Back in the mid-20th century,proposed that modern-day geographic ABO distributions are the consequence of past epidemics (6). Though severely understudied, research spanning decades has in fact uncovered several examples of antibodies that cross-react on microbial and histo-blood group antigens.
- Exposure to bacterial antigens stimulates anti-histo blood group antigen antibody titers ( ), suggesting the two, bacterial and blood group antigens, are antigenically related.
- As far back as 1971, researchers discovered that blood group O and A volunteers fed E.coli O86 had spike in anti-blood group B antibody titers (1), clearly indicating antigenic similarity between E.coli O86 and blood group B antigens.
- Histo-blood group and viral antigen similarities have been reported for SARS ( ) ( ) and virus ( ).
Such cross-reactivity can co-exist with immunological tolerance to one’s own histo-blood group antigens since sources of antibodies, thewith receptors capable of binding them would get deleted through the process of developmentally dictated tolerance.
Longer Answer With Some Examples Of Antibodies Cross-Reactive to Histo-Blood Groups & Microbial Antigens
Table below fromlists some linkages between disease-causing/associated microbial agents and blood groups.
O blood group is associated with resistance to severe malaria (11). As well, high percentage of O blood group individuals in malaria-endemic regions suggests selective advantage of having this blood group (). Malaria seems to have exerted selective pressure in blood group distribution ( ).
Anti-Vibrio cholerae antibody response induced by cholera vaccines was lower in blood group O compared to A individuals (14,). Epidemiological studies have found O blood group correlates with cholera disease severity (16, 17) fueling the speculation cholera selection pressure may account for the extremely low and high prevalence of histo-blood groups O and B, respectively, among people living in the Gangetic Delta ( , 19).
Lewis Blood Group Antigen: Rotavirus & Norovirus
Rotavirus infectivity appears to be highly dependent on histo-blood groups (). Non-B and secretor blood groups tend to be more susceptible to norovirus and rotavirus infection-associated gastroenteritis ( , , ). In a test of norovirus vaccine candidates, anti-histo blood group antibody titers in placebo group individuals positively correlated with protection while vaccinees with higher pre-challenge anti-histo blood group antibody titers had lower frequency of severe disease ( ). OTOH, secretor phenotype is associated with influenza, respiratory syncytial virus, echovirus ( ).
Anti-histo blood group antibodies could even function to neutralize viruses such as HIV, albeit in a blood group-specific manner. For example, an anti-blood group A monoclonal antibody could neutralize HIV viruses isolated from peripheral blood lymphocytes from blood group A donors but not B or O donors (24,).
The biomedical literature is pockmarked with sporadic reports of various vaccines triggering increase in anti-histo blood group antibodies, pneumoccocal vaccine (26) and tetanus and diphtheria toxoids () being cases in point. Again antigenic similarity explains the data. Streptococcus pneumoniae‘s polysaccharide capsule and pig stomach pepsin used back then to produce toxoids, both contain an A-like substance ( ).
Lifestyle & Diet Influence Anti-Histo Blood Group Antibodies
Some volunteers who took probiotic supplements developed high anti-histo blood group B antibody titers (). Turned out some bacterial strains in these supplements had antigenic similarity to histo-blood group B antigens.
Children who are fed intravenously for a long time have low to practically non-existent ABO antibodies, especially anti-B (29). Being essentially ‘sterile’, such nutrition alters and reduces gut microbiota suggesting major source of triggers for anti-histo blood group antibodies are gut microbiota. Interesting then that mean ABO titers have declined dramatically among those on present-day diet of processed, ‘pasteurized’ food compared to historical controls (30).
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