Prognostic Significance of Anti-D IgG Subclasses with Severity of Hemolytic Disease of Fetus and Newborn

Aim: According to the literature, HDFN cases with IgG1 and IgG3 have more severity compared to IgG2 and IgG4.The aim of this study was to investigate the influence of subclasses to IgG anti-D on the intensity of Hemolytic Disease of Fetus and Newborn (HDFN) in North Macedonia.

Materials and Methods: In retrospective and prospective studies, in a period of 10 years, from 2004 to 2014, there have been immunohematology tests performed on 22,009 samples on serums of pregnant women. The tests were performed with column agglutination method for: ABO blood groups, Rh phenotype, detection and identification of alloantibodies.

Results: From the total number of anti-D IgG1, IgG3 senzibilised pregnant women at 37.78% IgG1 and IgG3 were the reason for severe HDFN. At 17.77% of the total, cases with only IgG1 detected were responsible for varying intensities of hemolytic disease of the fetus (HDF), ranging from serious to mild, depending on the titer levels. The correlation of the titer to anti-D antibodies in the mother’s serum and the intensity of HDFN were researched in 48 newborns. The titers between 1:8 and 1:32 resulted in 3 cases of HDFN with symptoms of severe disease and in 4 cases there were no signs of HDFN. At 12 women that had a titer between 1:32 and 1:512, five of the newborns developed severe HDFN, and seven had symptoms of mild and weak intensity form. In 3 cases, the titer was higher than 512, and out of them one newborn had weak symptoms of HDFN, one developed severe HDFN and one ended with fetal death. Only in one case, the titer reached a value higher than 1000, and it ended with a fetal death.

Conclusions: The titers of the pregnant women's serum that are lower than 32 in most cases are not the cause for HDFN, instead of higher than 1000 which are usually provoke severe symptoms, so we can say that titers lower than 32 and those higher than 1000 can well predict HDFN. The titers of anti-D antibodies between 64 and 512 have no exact predictive value, by themselves. IgG1 and IgG3 subclasses of anti-D have no predictive value by themselves, and cannot foresee the outcome of HDFN. The severity of HDFN was significantly higher when IgG1 &/or IgG3 were present alone or in combination, compared to cases with the absence of IgG1 or IgG3. The research study results suggest that IgG1 and IgG3 should be included in a multi-parameter protocol for evaluation of the HDFN intensity. They can give a real assessment of the expected HDFN intensity in combination with the titer height and the significance of the antibodies.