Molecular Basis of Two Novel High Incidence Antigenson CD44 (Indian Blood Group System)

URN to cite this document:: urn:nbn:de:bvb:355-epub-513581
DOI to cite this document:: 10.5283/epub.51358

Poole, J. ; Tilley, L. ; Warke, N. ; Banks, J. ; Ahrens, Norbert

; Armstrong, D. ; Williams, M. ; Daniels, G.

Date of publication of this fulltext: 18 Jan 2022 07:35

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Abstract

Abstract

Introduction
CD44 is a ubiquitous glycoprotein that carries theantigens of the Indian (IN) blood group system, Inaand Inb.INantigens are weakly expressed onIn(Lu)Lu(a-b-) cells. A novelCD44 antigen/antibody was previously reported in two unrelatedMoroccan females (referred to here as cases A and B) [Pooleetal. (2002)Transfusion Medicine,12(Suppl. 1), 32]. We report afurther example of this novel antigen, two examples of anotherhigh incidence CD44 antigen and the molecular basis of both.
Case studies
We studied an antibody to an unidentified high inci-dence antigen in the serum of a pregnant Moroccan female (caseC). Her red cells and serum were mutually compatible with theantibodies and red cells from A and B and presumed to be CD44related. Two further cases of suspected CD44 antibodies werefound in the sera of pregnant females (cases D and E). The redcells and antibodies of D and E were mutually compatible butincompatible with those of A, B and C.
Results
The antibodies in C, D and E reacted strongly with allpanel cells by indirect antiglobulin test but were negative afterpapain treatment.In(Lu)Lu(a-b-) cells were negative or weaklyreactive. The antibodies were positive in the monoclonal antibodyimmobilisation of erythrocyte antigens (MAIEA) assay usingmonoclonal antibodies to CD44. The red cells of C and E hadweaker expression of Inbthan control cells. Sequencing of exons1–5 of theCD44gene revealed a single mutation in exon 3 for C(255C > G resulting in H85Q in the protein). Her mother, babyand two sisters were heterozygous 255C > G and two sisters hadthe wild type 255C. Sequencing of exon 3 ofCD44showed Aand B to be homozygous for the same 255C > G mutation.Sequencing of exons 1–5 ofCD44revealed a single mutation inexon 5 for D and E (488C > A resulting in T163R in the pro-tein). The father and two siblings of E were also homozygous488C > A and their red cells were compatible with E’s antibody.E’s mother and two siblings were heterozygous for 488C > A.
Conclusions
We report two novel CD44 antigens, which we pro-pose to be IN3 and IN4 in the IN blood group system. Lack ofIN3 results from a 255C > G mutation predicting H85Q inCD44. A, B and C made anti-IN3 during pregnancy. Absence ofIN3 antigen has only been found in Moroccans. Lack of IN4results from a 488C > A mutation predicting T163R in CD44.D and E made anti-IN4 during pregnancy.

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