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The missing link between autoimmune diseases and microchimerism


  • Hayashida, Kenji Second Department of Internal Medicine, Nagasaki University School of Medicine




autoimmune disease、 chronic graft-versus-host disease、 microchimerism、 gender bias、 bone marrow transplantation、 long-lived memory plasma cell、 mesenchymal stem cell、 H-Y antigen、 SPAG1、 anti-sperm antibody、 mitophagy、 exosome、 Eri15



Autoimmune diseases (AIDs) are characterized by being more common in females, but the cause is still unclear. Among the hypotheses explaining the reason, fetal microchimerism (Mc) involvement theory is the most convincing, but it is unclear how Mc cells impair recipients, and there is a significant missing link. The incidence of chronic graft-versus-host disease (cGVHD) after bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HSCT), which is the basis of the Mc theory of AIDs, also has a gender bias due to the combination of donor and recipient, but the cause is unknown. It is assumed that bone marrow cells (BMC) attacking allogeneic somatic cells (Soc) is the common cause of cGVHD and AIDs, and combining both genders gives gender bias. It is thought that examining which combination matches the actual gender bias and incidence of cGVHD and AIDs will validate the Mc etiology theory of AIDs.



The onset probability (OnP) is the sum of the encounter probabilities (EnP) of all combinations of BMC and allogeneic Soc caused by Mc. EnP is expressed as the product of the existence probability (ExP) of BMC and allogeneic Soc. ExP is expressed as the product of probabilities by factors such as the Mc pathway and cell aging involved in the existence of each cell. OnP was calculated for each gender combination of BMC and Soc to verify whether it matched the actual gender bias and incidence of cGVHD and AIDs.



The combination of female BMC attacking male Soc, a unidirectional heterosexual relationship, best matched the actual gender bias and incidence of cGVHD and AIDs.



The author hypothesized that the cause of AIDs is the same as cGVHD after BMT, and encounters between BMC and Soc in an allogeneic relationship brought about by Mc determine gender bias and incidence and simulated the encounter probability for each gender combination. As a result, it was found that assuming that female BMC attacks male Soc can  best explain the gender bias and incidence of cGVHD and AIDs. Furthermore, it is speculated that the target factor is H-Y antigen and the effector cell is H-Y antigen-specific long-lived memory plasma cells, and the author considered the missing link between AIDs and Mc.


I declare that I have no competing interests.

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Hayashida, Kenji、Second Department of Internal Medicine, Nagasaki University School of Medicine



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投稿日時: 2023-09-30 19:00:45 UTC

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