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Hematologists often rely on the results of a positive direct antiglobulin test to confirm a diagnosis of autoimmune hemolytic anemia, but immune hemolytic anemia can occur when no immunoglobulin is detectable by routine methods. Negative DATs in these patients may be due to a small quantity of IgG on their red blood cells (RBCs) (below detectable levels), or when low-affinity anti-IgG is present, or when the autoantibodies are IgA or IgM in nature. A panel of tests developed to detect immunoglobulins on these patients' RBCs may be performed in a few specialized laboratories. These tests can be helpful in instances whereby the clinical picture of AIHA seems obvious, but the laboratory values are misleading.

Background The numerous antigens in the Kell blood group system result from missense nucleotide changes in KEL. Antibodies to antigens in this system can be clinically important. We describe six probands whose plasma contained antibodies to high-prevalence Kell antigens, and discuss their relationship.

TSEN (MNS33) is a low-incidence antigen in the MNS blood group system encoded by hybrid glycophorin genes. TSEN is expressed by a unique amino acid sequence that results from the junction of GPA(58) to GPB(27), if the GPB carries S antigen. Until this study, only one example of anti-TSEN had been found. Antibody screening red blood cells (RBCs) positive for both S and s (ref. No. C873) reacted with four patient sera. Initially, the RBCs had been typed as S+s+, but later were typed as S-s+ in another laboratory. Two other RBC samples, one from a volunteer blood donor (D.L.), the other from a patient whose serum contained anti-En(a)FR (J.S.), also gave anomalous results when tested with anti-S. We suspected the presence of TSEN-positive hybrids on all three RBC samples.Reactive sera (O.B., E.C., S.K., R.F.) were tested against RBCs with normal MNS phenotypes and with TSEN-positive RBCs. The RBCs of D.L., J.S. and C873 were tested with anti-S whose reactivity with S+s+ TSEN+ RBCs had been established previously, and with the original example of anti-TSEN. Immunoblotting was performed on the C873, D.L. and J.S. RBC membranes using a monoclonal antibody to an epitope common to both glycophorin A and glycophorin B.The sera from O.B., E.C., S.K. and R.F. were strongly reactive on the indirect antiglobulin test with TSEN+ RBCs. The RBCs of C873, D.L. and J.S. were typed as TSEN+. Immunoblotting pattern of D.L. and C873 were consistent with TSEN heterozygotes, while that of J.S. was consistent with a TSEN homozygote.Based on the estimated number of screening events with C873 RBCs, the incidence of anti-TSEN is approximately 1 in 20,000 sera. The antibody is found in patients with and without documented exposure to allogeneic RBCs. All known examples of anti-TSEN are IgG, but their clinical significance is not known.