Anti-Tn-reactive immunoglobulin M (IgM) might form the first line of defense against SARS-CoV-2 infection (COVID-19): A proposed immunobiological background

The anti-Tn-reactive immunoglobulin M (IgM) might be identical to the nonimmune, germline-encoded blood group A-reactive isoagglutinin, expressed by the ancient poly- and autoreactive germline-encoded immunoglobulin M (IgM) in humans, which is serologically identical to anti-A from the C57BL/10 mouse and hardly arises in response to A-allelic genetic activities. This antibody, which does not occur in sera from blood group A individuals, may reflect the functions of metazoan defense proteins or lectins, which are considered non-self/self-recognition molecules that monitor expression of the cross-species evolutionary serological Tn antigen (<em>O</em>-GalNAcα1-Ser/Thr-R). Tn (T nouvelle) is an intermediate structure, almost exclusively expressed in tumor tissues and represents a key point of non-self-/self-recognition in metazoan species, while its complementary protein in human plasma, the anti-Tn-reactive IgM, mediates growth process monitoring. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades the human body via a trans-species Tn formation. The viral serine molecule, mobilized from the viral spike (S) protein by the host transmembrane protease serine subtype 2 (TMPRSS2) enzyme, was identified as a fusion molecule, essential for SARS-CoV-2 infection, wherein the syngeneic serine might be replaced by the pathogen molecule and the key point of nonself/self-recognition become the target of infection and source of aggressive autoimmunization. While it was argued that anti-Tn is protective against SARS-CoV-2, the hypothetical, cross-species enzyme-substrate competition between the host and viral serine molecule occurs preferentially in blood group A and the other non-O blood groups, whereas in blood group O(H), the foreignness of the hybrid Tn epitope is recognized as non-self by the corresponding anti-Tn-reactive IgM, which in concert with secondary anti-Tn-reactive immunoglobulin G (IgG) forms the first line of defense. <br>