Association of altered E RHCE*CE(697G, 712G, 733G, 744C) with altered D RHD*46C

OCHOA, GORKA; NOGUÉS, NÚRIA; MUÑIZ-DÍAZ, EDUARDO; TARRAGÓ, MARCEL; COTE, J; GOLDMAN, M; VEGE, S; WESTHOFF, C; VIETZ, C; LUJÁN BRAJOVICH, MELINA ELIANA; TRUCCO BOGGIONE, CAROLINA; COTORRUELO, CARLOS

Cancún

Congreso; XXXIIst International Congress of the ISBT; 2012

International Society of Blood Transfusion

Background The uncommon RHCE*cE(697G,712G,733G,744C) allele encodes an altered form of E antigen associated with RBC serologic E typing discrepancies (1). RHD*46C>T encodes a Trp16Arg change and RBCs have very weak or undetectable D antigen (2,3). A number of RHD and RHCE genetic variants have been found in association (in cis). Examples include RHD*DAR with RHCE*ceAR, and RHD*DIVa with RHCE*ceTI. Here we investigate the RHCE alleles in samples with variant RHD*46C, including the index cases (2,3). Materials & Methods Standard direct or indirect agglutination techniques in tube or gel and standard adsorption-elution techniques were used for serological tests. Antibody reagents and reactivity of the RBCs are listed. For molecular tests, we performed standard DNA sequencing, cDNA sequencing, PCR-RFLP, Rhesus box analysis, or allele-specific hybridization on an oligonucleotide microarray (BloodChip, Progenika). Results Anti-D Anti-E RH alleles Sample ID Ethnicity Reagent or Clone Reactivity Reagent or Clone Reactivity RHD RHCE A209-826 Caucasian(a) D175-2/D415 1E4 0 MS260 4+ RHD*46C RHCE*cE P3x249 0 deleted(b) RHCE*ce P3x61/P3x21223B10/P3x290/P3x35 0 ALBAclone Partial D 1+/0 Inconclusive 09-413 Caucasian(a) D175-2/D415 1E4 0 F561/1B11/2F6-4 0 RHD*46C RHCE*cE(697G,712G,733G,744C) GAMA401/F8D8 0 MS258/MS906(c) 3+ deleted(b) RHCE*ce MAD2 0 C2 3+ MF ALBAclone Partial D Inconclusive ML09-560 Caucasian D175-2/D415 1E4 0 GAMA402 0 RHD*46C RHCE*cE(697G,712G,733G,744C) GAMA401/F8D8 1+w/0(d) Single source 0 deleted RHCE*ce MS201/MS26 0 Single source 0 TH28/MS26 0 Single source 2+ MAD2 0 Single source 3+ DPK1 + P3x61/P3x21223B10/P3x290/P3x35 + D16 Caucasian(a) TH28/MS26 0 MS260 4+ RHD*46C RHCE*cE(697G,712G,733G,744C) RUM-1 1+/0 MS80/MS258 0 deleted(b) RHCE*ce ALBAclone Partial D Inconclusive C7 Caucasian(a) TH28/MS26 0 MS260 4+ RHD*46C RHCE*cE Adsorption-Elution + deleted(b) RHCE*ce C17 Caucasian(a) TH28/MS26 0 MS260 4+ RHD*46C RHCE*cE Adsorption-Elution + deleted(b) RHCE*ce (a) Most likely Caucasian, although some Native American ascent cannot be ruled out (b) Determined by family studies or by Rhesus box analysis (c) Anti-E reactivity associates with MS906 (d) Anti-D reactivity at IS (GAMA401 IgM) MF: Mixed Field. Conclusions In six unrelated and geographically disparate samples with variant RHD*46C, three had variant RHCE*cE(697G,712G,733G,744C) in cis, and three had conventional RHCE*cE, presumed in cis. The low population frequency of both variant alleles strongly suggest a genetic association between them. Description of in cis associations is important for the identification of antibodies to high-frequency antigens in the Rh system, and facilitates matching efforts for patients with rare or uncommon genotypes.