Martha Rae Combs

Erythrocyte autoantibodies in paediatric patients with sickle cell disease receiving transfusion therapy: frequency, characteristics and significance

The formation of erythrocyte autoantibodies following transfusion therapy has been described in case reports and small series. To determine the frequency, serological characteristics, and clinical significance of this phenomenon in paediatric patients with sickle cell disease, we analysed the patient database at the Duke University Pediatric Hematology Clinic. We identified children who received multiple erythrocyte transfusions, then reviewed clinical records to identify children who developed erythrocyte autoantibodies in association with transfusions. Among 184 paediatric patients who received multiple erythrocyte transfusions, 14 children (7.6%) developed warm (IgG) erythrocyte autoantibodies. Median transfusion exposure at the time of autoantibody formation was 24 erythrocyte units, range 3–341 units. The autoantibody reacted as a panagglutinin in 11 cases but had anti‐e specificity in three patients. Surface complement also was detected in five patients. Clinically significant haemolysis was documented in four patients, each of whom had both surface IgG and C3 detected. The development of erythrocyte autoantibodies was associated with the presence of erythrocyte alloantibodies. Formation of warm erythrocyte autoantibodies in association with transfusions is not rare in paediatric patients with sickle cell disease. Clinicians should be aware of this complication and recognize that the presence of surface C3 is often associated with significant haemolysis.

Lack of clinical significance of “enzyme-only” red cell alloantibodies

In a retrospective study on samples from 10,000 recently transfused patients, 35 samples were found to contain an antibody that reacted with ficin‐treated red cells but was not demonstrable by low‐ionic‐ strength saline solution and indirect antiglobulin test (LISS‐IAT). In those 35 patients, the specificity of the antibody was such that each patient would have been transfused with antigen‐negative blood had the antibody reacted in LISS‐IAT. Tests on red cells from the units already transfused showed that 19 patients had among them received, by chance, 32 antigen‐positive and 74 antigen‐negative units. The remaining 16 patients had among them received 57 units that were, again by chance, all antigen negative. One patient given antigen‐positive blood suffered a delayed transfusion reaction; in two others the antibodies became LISS‐IAT active after transfusion. However, similar changes to the LISS‐ IAT‐active state were seen with two antibodies of patients given only antigen‐negative blood. Also found in the 10,000 patients were 28 clinically insignificant antibodies, 77 sera in which the antibody was too weak to identify, and 216 autoantibodies that reacted only with ficin‐treated red cells. These data support a belief, generally held in the United States but not necessarily elsewhere, that the use of protease‐treated red cells for routine pretransfusion tests creates far more work than the accrued benefits justify.

Lack of Duffy antigen expression is associated with organ damage in patients with sickle cell disease

BACKGROUND: The Duffy glycoprotein (Fy) on red blood cells (RBCs) has been hypothesized to promote clearance of inflammatory cytokines, which may play a role in the pathogenesis of vasoocclusion in sickle cell disease (SCD). Persons with the African‐type Fy(a–b–) phenotype—whose RBCs lack expression of Duffy—may less efficiently clear inflammatory cytokines. Therefore, the Duffy‐negative genotype may be associated with more severe disease among patients with SCD.

Alloimmunization in sickle cell disease: changing antibody specificities and association with chronic pain and decreased survival.

Alloimmunization remains a significant complication of transfusion and has been associated with multiple factors, including inflammation, an important pathophysiologic mechanism in sickle cell disease (SCD). We explored whether alloimmunization is associated with disease severity in SCD.

JMH variants: serologic, clinical, and biochemical analyses in two cases

BACKGROUND: JMH is a high‐frequency red cell blood group antigen that resides on a 76‐ to 80‐kDa glycosylphosphatidylinositol‐linked protein also known as CDw108. Antibodies with JMH specificity are often autoimmune and are usually, if not always, clinically benign. Some individuals with JMH‐variant antigen produce alloantibodies to JMH, but little evidence concerning their clinical significance is available. This article reports on two patients who express a JMH‐variant antigen and produced alloanti‐JMH.

Rh haplotypes that make e but not hrB usually make VS.

Background and objectives: The Rh phenotypes hrB– and VS+ are both rare in Whites but more common in Blacks. The high‐incidence antigen hrB is present on most red cells that are e+. The presence of VS on red cells is associated with an aberrant expression of e, often called eS. Materials and methods: Using conventional serologic methods, including a monoclonal anti‐hrB‐like antibody, we studied 65 e+ samples that were apparently hrB–. Results: Of the 65, we found that 59 (91%) were VS+. Recent findings have indicated that in VS+ persons a change from leucine to valine occurs at amino acid 245 of the RHCE‐encoded polypeptide. While this residue is predicted to lie within the red cell membrane bilayer, the change presumably affects alanine 226 (that is present when e is expressed) in such a way that eS is seen. Conclusions: Our findings suggest that the change from e to eS may result in nonexpression or marked depression of expression of hrB that is, perhaps, an epitope of e. While the molecular basis of the hrB– phenotype is not known, it is unlikely that the leucine‐to‐valine change at residue 245, resulting in the aberrant form of e, explains all hrB– samples. First, hrB– VS+ and hrB– VS– samples must differ. Second, some hrB– VS+ samples are C+, some are C–. Presumably diverse molecular bases are involved in hrB– phenotypes.

IgA‐mediated autoimmune hemolytic anemia in an infant

Autoimmune hemolytic anemia (AIHA) is characterized by the presence of autoantibodies, most frequently of the IgG isotype, directed against erythrocyte surface antigens. The direct antiglobulin test (DAT) is the critical laboratory test for the diagnosis of AIHA, but is negative in 3–11% of cases. In these cases of DAT negative AIHA, a wider spectrum of clinical data including more specialized testing for erythrocyte autoantibodies may be required. We describe the unique and challenging case of an infant with corticosteroid‐responsive, DAT negative AIHA, in which specialized gel card testing identified an isolated IgA autoantibody on the erythrocyte surface. Pediatr Blood Cancer 2011;56:837–839.