(P-IG-15) Clinically Benign Antibody Directed at MN CHO in a Child with Sickle Cell Disease Complicates Finding Compatible Blood

Background/Case Studies: The MN CHO blood group collection (ISBT 213) consists of 6 antigens (Ag):Hu, M₁, Tm, Can, Sext, Sj. In 1934 Landsteiner [J Immunol 27,459] described an antibody (Ab) made from immunized rabbits that reacted only with RBCs from Blacks of African descent. The Ags are associated with atypical glycosylation of glycophorin A (GPA) dependent on GlcNAc- linked O-glycosidic oligosaccharides; the underlying genetic basis is unknown. Ab to MN CHO Ags aren’t associated with clinically significant hemolysis. We studied a sample from a 7-year-old with sickle cell disease (SCD) enrolled in a clinical trial providing RH genotype-matched RBCs from Black or Hispanic donors for chronic transfusion. At 7^th on-study transfusion, her plasma had a negative (neg) Ab screen but incompatible crossmatches (XM) with RH genotype-matched RBCs.

Study

Design/Methods: Serology was by standard hemagglutination including trypsin treated RBCs. Rare RBCs were from in-house collection. R0, Fy(a-b-) or S-s- test RBCs were presumed from Blacks. RBC units were from donors who self identified as Black or Hispanic and had RH genotype and PreciseType HEA.

Results/Findings: Patient plasma reacted 1+ in IgG gel XM; comparing the patient’s HEA phenotype with the HEA types of the incompatible RBC and 6 RBCs transfused prior provided no immediate insight on potential Ab. In IRL testing, mi+-1+ reactivity in PEG IAT with 3 of 7 RBCs was seen; 1 M₁+ RBC and 2 RH genotype-matched Black donors. This suggested an Ab to an Ag expressed on RBCs with atypical glycosylation. Trypsin treated RBCs were neg consistent with anti-M₁ or another MN CHO Ag. Additionally, 2 of 4 RBCs from Blacks,1 additional M₁+,1 Tm+ and 1 of 8 random RBCs reacted 1+ by IgG gel; trypsin treated RBCs were neg. On subsequent transfusion and splenectomy, 9 of 19 RH genotype-matched RBCs were XM incompatible (47%,Table 1); 8 donors self identified as Black and 1 as Hispanic, consistent with reported prevalence of MN CHO variant glycosylation.




Table 1 Compatibility testing

Transfusion #		# units needed	# units XM’d	# Incompatible	# Transfused
7		1	2	1	1
8		1	4	3	1
9		1	1	0	1
10		1	2	1	1
11		1	4	2	1
12		1	3	1	2
Splenectomy		1	3	1	0
Total		7	19	9	7

Conclusions: We identified a MN CHO Ab that was causative in crossmatch incompatibility in a transfusion dependent child with SCD. The Ags are expressed on GPA and represent altered glycosylation found on 25-45% of RBCs from Black donors vs < 1% in Caucasians. Like anti-M the Abs aren’t generally clinically significant. Patients with SCD often rely on a similar donor pool to find compatible Rh and K matched RBCs. It’s important to identify these specificities for clinical decision making, as crossmatch reactivity can drastically reduce the number of apparent compatible donors particularly for patients who require multiple antigen negative RBCs likely to be found in a minority donor pool.