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>

抗Tn反应性免疫球蛋白M（anti-Tn-reactive immunoglobulin M, IgM）可能与非免疫性、生殖系编码（germline-encoded）的血型A反应性同种凝集素（isoagglutinin）完全一致，该凝集素由人类古老的多反应性且自身反应性的生殖系编码免疫球蛋白M（IgM）表达，其血清学特性与C57BL/10小鼠（C57BL/10 mouse）来源的抗A抗体一致，且几乎不会因A等位基因的遗传活性而诱导产生。这类抗体不存在于A型血个体的血清中，其功能可能对应后生动物（metazoan）防御蛋白或凝集素（lectin）——这类分子被认为是非己/己识别分子（non-self/self-recognition molecules），用于监测跨物种进化血清学Tn抗原（Tn antigen，化学结构为O-GalNAcα1-Ser/Thr-R）的表达。
Tn（T nouvelle）是一种中间结构，几乎仅在肿瘤组织中表达，是后生动物体内非己/己识别的关键位点；而人类血浆中对应的抗Tn反应性IgM则介导生长过程的监测。
严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2, SARS-CoV-2）通过跨物种Tn形成机制入侵人体。研究证实，宿主跨膜蛋白酶丝氨酸亚型2（transmembrane protease serine subtype 2, TMPRSS2）可从病毒刺突蛋白（spike protein, S蛋白）上解离出病毒丝氨酸分子，该分子是病毒感染必需的融合分子（fusion molecule）；此时同源丝氨酸（syngeneic serine）可被病原体分子替代，而非己/己识别的关键位点便成为感染的靶点以及侵袭性自身免疫（autoimmunization）的诱因。
尽管有观点认为抗Tn对SARS-CoV-2具有防护作用，但宿主与病毒丝氨酸分子之间的假想跨物种酶-底物竞争（enzyme-substrate competition）更易发生在A型血（blood group A）及其他非O型血人群中；而在O(H)型血（blood group O(H)）人群中，杂交Tn表位（epitope）的异源性会被相应的抗Tn反应性IgM识别为非己，这类IgM与继发性抗Tn反应性免疫球蛋白G（immunoglobulin G, IgG）协同构成机体的第一道防御防线。