Antibodies against high frequency Gerbich 2 antigen (anti-Ge2): A real challenge in cross matching lab.

Transfusion management of patients' alloimmunized against high-prevalence erythrocyte antigens is often problematic in emergency situations. Gerbich (Ge) is very common blood group system and Gerbich-2 (Ge-2) antigen present in high frequency and outside Papua New Guinea population, Ge-2 negative population almost nil. To manage such kind of problems with real emergencies, implementation of rare donor registry program, cryopreservation of red cells of rare donors and biological cross matching to assess significance of these antibodies is warranted.

Introduction

Transfusion management of patients’ alloimmunized against high-prevalence erythrocyte antigens is often problematic in emergency situations.

Gerbich (Ge) is very common blood group system and outside Papua New Guinea, Ge negativity is very uncommon. They are located on either or both of the red cell membrane sialoglycoproteins, glycophorin C (GPC) and glycophorin D (GPD) or on closely related glycophorins.

Rosenfield et al., Cleghorn et al., McLoughlin et al., and Race et al., in their studies, screened 28,331 blood samples from White population of English, Danes, New Zealand and California respectively with anti-Ge-2 antisera and none of them found negative to Ge-2 antigen, i.e. 100% positivity in the white studied population.[1] On the other hand Booth et al.,[2] studied Melanesians of Papua New Guinea in Sepik, Morobe regions and Highlands in 3,110 blood samples, of them 700 (22.5%) were negative for Ge-2 antigen, indicating Papua New Guinea race had highest Ge-2 antigen negative in the world.

Anti Ge-2 is the most common Gerbich alloantibody. It is the antibody characteristic of Ge: –2, 3, 4 phenotype (Yus), but is also the most frequently encountered antibody in the Ge: –2, –3, 4 phenotype (Gerbich) and Ge: –2, –3, –4 phenotype (Leach).

Studies supported that harmless nature of Ge antibodies but in few studies suggested that antibodies to Gerbich antigen may be a rare cause of hemolytic disease of fetus and newborn.[34]

Case Report

A 27-year-old Saudi Arabian woman P 2+0 was admitted in gynecology and obstetrics department with the diagnosis of dysfunctional uterine bleeding (DUB) with ovarian cyst, requested 2 units of packed red cells on 26-06-2005. On blood grouping, she was typed as O Rh D+ve and her hemoglobin was 11.2 gm/dl. In cross matching laboratory, her serum was found to be reactive with O Rh D+ve packed cells units tested in indirect Coombs’ testing (IAT) phase with polyspecific (IgG + C3d) Coombs’ gel card (DiaMed AG, Switzerland) with 3+ agglutination, but no incompatibility in immediate spin and 37° C phase in tube technique. More than 90–O Rh D+ve units were cross matched, none of them found compatible to this patient.

On laboratory workup, her direct Coombs’ test (DCT) and auto control (AC) were negative and antibody screening (3 cells) and antibody identification by 11 cells panel (DiaMed AG, Switzerland) showed uniform 3+ agglutinations with all 3 screening, as well as 11 panel cells in indirect Coombs’ testing (IAT) phase with polyspecific (IgG + C3d) Coombs’ reagent, but no agglutinations in immediate spin and 37° C phase.

Panels of Rare Antisera (Diamed AG, Switzerland) were used for the presence of alloantibodies. Her probable Rh genotype was R2R2 (DcE/DcE) with extended phenotype of Le (a–b+), P1+, M+, N+, S+, s–, K– k+, Fy (a+b–), Jk (a+b+), Ge: –2, 3, 4 (Yus Phenotype).

On identification panel anti – Ge2 antibodies were identified, which was reactive in indirect antiglobulin phase (IAT). The presence of common alloantibodies were excluded by using papain treated cells, however, unable to exclude the presence of anti–s antibodies. We concluded that this patient should receive Ge–2 and s antigen negative blood.

Because of rarity of Ge–2 negative donors, patients siblings were call for screening, six siblings were tested and none of them found compatible to the patient. Patient's hemoglobin was 11.2 gm/dl and after consultation with director of gynecology and obstetrics department, two units of autologous whole blood were collected on day 0 and 14 from surgery date. The patients also prescribed oral iron preparation to boost her hemoglobin. Surgery was done on day 30, calculated from the dated of first unit collection. Two autologous whole blood units were issued and transfused to the patient peri–operatively. The surgery was successful and we did not receive further request for this patient.

Discussion

In immunohematology, there is a number of RBC blood groups of very high frequency for which the transfusion significance of alloimmunization is uncertain. High frequency antigens classify as having frequency greater than 90% while those antigens have frequency in excess of 99% described as “Public antigens”, on the other hand antigens having frequency less than 1% called “Low frequency antigens” and less than 0.25% defined as “Private antigens”.[1]

Gerbich system began as a simple inherited blood group antigen and consists of 11 antigens, six of very high frequency, present in >90% of population (Ge 2, Ge 3, and Ge 4, GEPL, GEAT, and GETI), while five are of low frequency, present in <1% of population (Wb, Lsa, Ana, Dha, and GEIS). The antibodies that Ge negative individuals produce may be immune or occur without red cell stimulation. Anti-Ge is usually IgG but may have an IgM component.[4] There are three rare phenotypes described, in which red cells lack one or more of the three high frequency Gerbich antigens, Ge: –2, 3, 4 (Yus Phenotype), Ge: –2, –3, 4 (Gerbich Phenotype) and Ge: –2, –3, –4 (Leach Phenotype).[1]

Our patient's origin was Saudi Arabia and her Ge phenotype was Ge: –2, 3, 4 (Yus Phenotype). This phenotype has been found in white population (including Arabs, a Turkish Cypriot, and a Middle East Jews) and in black people (including Ethiopian Jews). Family studies demonstrates that Yus phenotype is inherited.[2]

Conclusion

The clinical significance of the high frequency antibodies is variable. To manage such kind of problems with real emergencies, we should think seriously for the implementation of rare donor registry program and cryopreservation of red cells of rare donors, which is in process of implementation at our center, as well as serious note on the implementation of biological cross matching to assess significance (i.e., harmful or harmless nature) of these antibodies, if high frequency antigen negative blood is not available.