LMP7 polymorphism may modify the presentation and clinical impact of minor histocompatibility antigens in matched related hematopoietic stem cell transplantation

• DOI: 10.1016/j.cellimm.2021.104329
• Publication Date: 2021-03-09T20:49:35Z
• Authors: Ghada I. Mossallam; Raafat Abdel Fattah; Mahmoud Bokhary; Manar Moneer; Hossam K. Mahmoud
• Keywords: Adult; Male; Antigen Presentation; 0303 health sciences; Polymorphism, Genetic; Adolescent; Genotype; Incidence; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Middle Aged; 3. Good health; Minor Histocompatibility Antigens; 03 medical and health sciences; Child, Preschool; Histocompatibility; Acute Disease; Humans; Female; Genetic Predisposition to Disease; Child; Oligopeptides; Genetic Association Studies

Differential expression of minor histocompatibility antigens between the recipient and donor determines their disparity and can be modified by immunoproteasomes that regulate their processing and presentation. We examined the impact of HA-1 and HA-8 disparity, and immunoproteasome LMP7 polymorphism in 130 pairs. In multivariate analysis, HA-1 disparity showed a statistically significant association with an increased incidence of acute graft-versus-host disease (aGVHD) II-IV (p = 0.043, HR: 3.71, 95%CI = 1.04-13.26), while LMP7-Q/Q showed a trend toward increased incidence of aGVHD compared to LMP7-Q/K and K/K genotypes (p = 0.087, HR: 2.36, 95%CI = 0.88-6.31). All HA-1 and HA-8 disparate patients who developed aGVHD had the LMP7-Q/Q genotype. No significant association could be detected between HA-1, HA-8, or LMP7 and chronic GVHD, relapse-free survival (RFS), overall survival (OS), or transplant-related mortality (TRM). In conclusion, we suggested an association between the HA-1 disparity and the risk of developing aGVHD with a possible modifying effect of LMP7.