RESUMEN
INTRODUCTION: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. CASE PRESENTATION: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. DISCUSSION/CONCLUSION: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.
RESUMEN
BACKGROUND: Primary cold agglutinin disease (CAD) is a monoclonal antibody (M-protein) and complement-mediated chronic hemolytic disease process. Antibody glycosylation can play a role in both antibody half-life and complement fixation. Recently, M-protein light chain (LC) glycosylation has been shown to be associated with AL amyloidosis. We hypothesized that M-protein LC glycosylation is also associated with cold agglutinin (CA) titers and CA-mediated hemolysis. STUDY DESIGN AND METHODS: A cross-sectional study of patients undergoing CA titer evaluation underwent mass spectrometric analysis for M-proteins and M-protein LC glycosylation. A subset of serum samples also underwent evaluation for the ability to trigger cold hemolysis in vitro. M-protein and M-protein LC glycosylation rates were compared across CA titer groups, clinical diagnosis, direct antiglobulin testing (DAT) results, and cold in vitro hemolysis rates. RESULTS: Both M-protein and M-protein LC glycosylation rates significantly differed across CA titer groups with the highest rates in those with elevated CA titers. M-protein LC glycosylation occurred almost exclusively on IgM kappa M-proteins and was significantly associated with positive DAT results and a clinical diagnosis of CAD. Cold in vitro hemolysis was demonstrated in two patients who both had a CA titer of more than 512 but there was no significant association with CA titer group or M-protein LC glycosylation status. CONCLUSION: M-protein LC glycosylation is significantly associated with higher CA titer levels. Given the role that antibody glycosylation can play in antibody half-life and complement fixation, further studies are needed to clarify the effects of LC glycosylation within the context of CAD.
