[Clinical significance of irregular antibodies]

Antibodies directed against red blood cell antigens other than those of the ABO system are referred to as irregular antibodies. Among these, IgG-type immune antibodies that are active at 37°C are considered to have high clinical significance. Irregular antibodies are typically detected using the indirect anti-globulin test (IAT), which offers high sensitivity for IgG detection. Although detection of irregular antibodies in the IAT is considered clinically significant, not all IAT-positive antibodies cause hemolytic transfusion reactions (HTR) or hemolytic disease of the fetus and newborn (HDFN). IgG is classified into four subclasses-IgG1 through IgG4. In this study, the characteristics of irregular antibodies were analyzed according to their subclasses using flow cytometry, and a monocyte phagocytosis assay was performed. The results revealed that both the IgG3-only and the IgG1+IgG3 combination types were strongly associated with adverse hemolytic effects and had high clinical relevance. Furthermore, in cases of HDFN, higher levels of IgG3 on fetal red blood cells correlated with increased phagocytosis rates and more severe disease progression. These findings suggest that IgG subclass analysis may serve as an important indicator for predicting the severity of HTR and HDFN.