Association of the CD45 C77G Polymorphism with Development of Autoimmune Disease and Transplant-Related Outcomes

Introduction The CD45 C77G (SNP# rs17612648) polymorphism is present in ∼3% of individuals of European ancestry, impairs formation of the CD45RO isoform, and has been controversial regarding its association with autoimmune disease. Methods We analyzed clinical samples from 2019 to 2022 in the UAB Cellular Immunobiology Laboratory, identifying patients with the characteristic flow cytometry pattern for this polymorphism. Results We identified 23 pediatric females (PF) and 22 pediatric males (PM) with C77G, compared with 817 PF and 1,057 PM with C77C. Similarly, we identified 38 adult females (AF) and 10 adult males (AM) with C77G, compared with 1,001 AF and 314 AM with C77C. The frequency of adults with C77G analyzed in our lab was significantly greater than that of the general Alabama population (p = 0.0025). While the frequency of AF with C77G was greater than PF with C77G (p = 0.0051), it was comparable with AF with C77C relative to male counterparts (p = 0.7314). Autoimmune conditions or serologic markers (positive ANA or RF) were present in 33% (15/45) of pediatric and 52% (25/48) of adult C77G patients. Pediatric C77G patients with autoimmunity had significantly more hematological/oncological comorbidities (3/15, 20%; p = 0.0321) and history of organ transplant (6/15, 40%; p = 0.0035) compared with pediatric C77G patients without autoimmunity (0/30, 0% and 1/30, 3%, respectively). Three pediatric C77G autoimmune patients had received hematopoietic stem cell transplant (HSCT) for aplastic anemia or leukemia, with two developing severe graft-versus-host disease (alloimmunity) and the other developing Graves’ disease requiring thyroidectomy. Additional pediatric C77G patients with autoimmunity include two thymic transplant recipients that developed complications during the T cell reconstitution period (one with transverse myelitis, the other with macrophage activation syndrome and autoimmune hemolytic anemia). Adult autoimmune and non-autoimmune C77G populations did not differ in overall comorbidities, and no adult C77G patient had a history of hematopoietic cell or solid organ transplantation. Conclusions The presence of the CD45 C77G polymorphism in pediatric patients with autoimmune/alloimmune disease, particularly following HSCT or thymic transplant, suggests a potential role for this variant in influencing T cell maturation within the thymus and in predisposing for autoimmunity.