Impact of HLA-G +3142C>G on the development of antibodies to blood group systems other than the Rh and Kell among sensitized patients with sickle cell disease.

BACKGROUND: Patients' inflammatory history is an important factor underlying red blood cell (RBC) alloimmunization, which is a frequent transfusion complication among individuals with sickle cell disease (SCD). HLA-G has been associated with different inflammatory and auto - immune diseases. Our goal was to verify whether the HLA-G + 3142 C>G and 14-bp Ins/Del variations are associated with RBC antibody development among SCD patients. METHODS: This was a single-center case-control study. SCD patients were randomly selected for the study and divided into two groups: 'Alloimmunized' and 'Nonalloimmunized' depending on the presence of irregular antibodies. The 'Alloimmunized'group was further divided into two subgroups according to the presence of only antibodies against the Rh and Kell blood group systems or the existence of antibodies to antigens of the other blood group systems. RESULTS: A total of 213 patients were included in the study (110 alloimmunized and 103 non-alloimmunized). The 'Alloimmunized' and 'Non-alloimmunized' groups did not differ statistically regarding the HLA-G + 14 bp Ins/Del ( p = 0.494) and + 3142 C>G ( p = 0.334). Individuals who had only antibodies against the Rh and Kell antigens had a frequency of HLA-G + 3142GG genotype almost twice as high compared to the groupwith antibodies against less immunogenic antigens ( p = 0.043). CONCLUSIONS: The genotype frequency of HLA-G + 3142 C>G differs among alloimmunized SCD patients, depending on the presence of antibodies against low immunogenic RBC antigens. This highlights a possible role played by the HLA-G molecule in the RBC alloimmunization process.

Direct antiglobulin test in the differential diagnosis of ABO hemolytic disease of the newborn: an important tool with high negative predictive value.

BACKGROUND: Hemolysis due to ABO incompatibility is an important differential diagnosis in newborns presenting with jaundice. Clinical studies evaluating ABO hemolytic disease of fetus and newborn (ABO-HDFN) question the diagnostic value of the direct antiglobulin test (DAT) in this situation. GOALS: To determine the clinical and laboratorial findings associated with the occurrence of ABO-HDFN and to evaluate the accuracy of DAT as a diagnostic tool. METHODS: This was a nested case control study with a cohort of 4122 newborns. Clinical and immunohematological data were retrieved from medical files including clinical and laboratorial factors associated with ABO-HDFN. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of positive DAT were calculated. RESULTS: Among the 4122 newborns, 44 had the diagnosis of ABO-HDFN. Positive DAT, group O mother and group A newborn were significantly associated with the occurrence of neonatal jaundice and this association persisted in a multivariable model (p-value <0.001). DAT presented 65.85 % sensitivity, 96.28 % specificity, 16.9 % PPV and 99.6 % NPV for the diagnosis of ABO-HDFN. There were no cases of positive DAT in cases other than O/A and O/B incompatibilities. The newborn hemoglobin was significantly lower in O/A incompatibility (p-value <0.001). CONCLUSION: Positive DAT, mother of group O and newborn of group A are independent risk factors associated with ABO-HDFN. DAT exhibited high NPV for the diagnosis of this complication. Thus, performing DAT in newborns with O/A and O/B incompatibilities is a cost-effective strategy that can be applied as routine by blood banks.