Volume 47, Issue 7 pp. 1306-1311

Two missense mutations in the CD44 gene encode two new antigens of the Indian blood group system

Joyce Poole

Joyce Poole

From the Bristol Institute for Transfusion Sciences and International Blood Reference Laboratory, National Blood Service, Bristol, UK; Sanquin Blood Supply, Diagnostic Services, Amsterdam, the Netherlands; Charité, Institut für Transusionsmedizin, Berlin, Germany; and the National Blood Service, Leeds Centre, Leeds, UK.

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Louise Tilley

Louise Tilley

From the Bristol Institute for Transfusion Sciences and International Blood Reference Laboratory, National Blood Service, Bristol, UK; Sanquin Blood Supply, Diagnostic Services, Amsterdam, the Netherlands; Charité, Institut für Transusionsmedizin, Berlin, Germany; and the National Blood Service, Leeds Centre, Leeds, UK.

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Nicole Warke

Nicole Warke

From the Bristol Institute for Transfusion Sciences and International Blood Reference Laboratory, National Blood Service, Bristol, UK; Sanquin Blood Supply, Diagnostic Services, Amsterdam, the Netherlands; Charité, Institut für Transusionsmedizin, Berlin, Germany; and the National Blood Service, Leeds Centre, Leeds, UK.

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Frances A. Spring

Frances A. Spring

From the Bristol Institute for Transfusion Sciences and International Blood Reference Laboratory, National Blood Service, Bristol, UK; Sanquin Blood Supply, Diagnostic Services, Amsterdam, the Netherlands; Charité, Institut für Transusionsmedizin, Berlin, Germany; and the National Blood Service, Leeds Centre, Leeds, UK.

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Marijke A.M. Overbeeke

Marijke A.M. Overbeeke

From the Bristol Institute for Transfusion Sciences and International Blood Reference Laboratory, National Blood Service, Bristol, UK; Sanquin Blood Supply, Diagnostic Services, Amsterdam, the Netherlands; Charité, Institut für Transusionsmedizin, Berlin, Germany; and the National Blood Service, Leeds Centre, Leeds, UK.

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José A.C.M. Van Der Mark-Zoet

José A.C.M. Van Der Mark-Zoet

From the Bristol Institute for Transfusion Sciences and International Blood Reference Laboratory, National Blood Service, Bristol, UK; Sanquin Blood Supply, Diagnostic Services, Amsterdam, the Netherlands; Charité, Institut für Transusionsmedizin, Berlin, Germany; and the National Blood Service, Leeds Centre, Leeds, UK.

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Norbert Ahrens

Norbert Ahrens

From the Bristol Institute for Transfusion Sciences and International Blood Reference Laboratory, National Blood Service, Bristol, UK; Sanquin Blood Supply, Diagnostic Services, Amsterdam, the Netherlands; Charité, Institut für Transusionsmedizin, Berlin, Germany; and the National Blood Service, Leeds Centre, Leeds, UK.

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Diane Armstrong

Diane Armstrong

From the Bristol Institute for Transfusion Sciences and International Blood Reference Laboratory, National Blood Service, Bristol, UK; Sanquin Blood Supply, Diagnostic Services, Amsterdam, the Netherlands; Charité, Institut für Transusionsmedizin, Berlin, Germany; and the National Blood Service, Leeds Centre, Leeds, UK.

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Mark Williams

Mark Williams

From the Bristol Institute for Transfusion Sciences and International Blood Reference Laboratory, National Blood Service, Bristol, UK; Sanquin Blood Supply, Diagnostic Services, Amsterdam, the Netherlands; Charité, Institut für Transusionsmedizin, Berlin, Germany; and the National Blood Service, Leeds Centre, Leeds, UK.

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Geoff Daniels

Geoff Daniels

From the Bristol Institute for Transfusion Sciences and International Blood Reference Laboratory, National Blood Service, Bristol, UK; Sanquin Blood Supply, Diagnostic Services, Amsterdam, the Netherlands; Charité, Institut für Transusionsmedizin, Berlin, Germany; and the National Blood Service, Leeds Centre, Leeds, UK.

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First published: 02 May 2007
Citations: 19
Geoff Daniels, PhD, FRCPath, Bristol Institute for Transfusion Sciences, National Blood Service, Southmead Road, Bristol BS10 5ND, UK; e-mail: [email protected].

Abstract

BACKGROUND: Blood samples were referred over a 10-year period from five patients whose serum samples contained antibodies to unidentified high-incidence antigens. Three patients (A, B, C) were of Moroccan origin and their antibodies and red blood cells (RBCs) were mutually compatible, but incompatible with those of the other two patients (D, E), who were of Pakistani origin. The antibodies and RBCs of D and E were mutually compatible, but incompatible with those of Patients A, B, and C. All the antibodies were detected during pregnancy.

STUDY DESIGN AND METHODS: Serologic tests, including the use of enzyme-treated and chemically modified RBCs, suggested a relationship to CD44 (Indian blood group system). The monoclonal antibody immobilization of erythrocyte antigens (MAIEA) assay with monoclonal CD44 antibodies, immunoblotting of RBC membranes, and CD44 gene sequencing were carried out.

RESULTS: Positive reactions in the MAIEA assay confirmed that the patients' antibodies are directed at CD44. Immunoblotting with two of the antibodies gave positive reactions of identical size to monoclonal anti-CD44 and failed to react with the RBCs of a CD44-deficient patient. One of the antibodies reacted with purified CD44. Sequencing of Exons 1 to 5 of CD44 revealed 255C>G in Exon 3 for A, B, and C encoding H85Q and 488C>A in Exon 5 for D and E encoding T163R.

CONCLUSION: Two novel CD44 antigens of high incidence have been identified: IN3 (INFI) and IN4 (INJA) in the IN (Indian) blood group system. Lack of IN3 and IN4 results from homozygosity for mutations encoding H85Q and T163R in CD44, respectively.

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