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Allergy, immunity, and infection

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G219 T CELL RECEPTOR OLIGOCLONALITY IN THE PRESENCE AND ABSENCE OF RECOMBINASE ACTIVATING GENE DEFECTS IN OMENN SYNDROME (OS)

A. R. Gennery1, A. P. Williams2, E. Hodges2, A. Villa3, J. J. M. van Dongan4, A. J. Cant1, J. L. Smith2. 1Department of Paediatrics, Newcastle General Hospital, Newcastle upon Tyne, NE4 6BE; 2Wessex Immunology Service, Southampton University Hospitals, Southampton SO16 6YD; 3ITBA, CNR, Cervi 93, Italy; 4Erasmus University, Rotterdam, 3000 DR Rotterdam, The Netherlands

Introduction: OS, a form of severe combined immunodeficiency syndrome characterised by hepatosplenomegaly, lymphadenopathy, an erythematous rash, eosinophilia, and elevated IgE, is characterised by oligoclonal T cell expansions and defects in the recombinase genes RAG1 and RAG2. We describe nine cases of OS with typical clinical and immunological features but with a RAG defect being identified in only two cases.

Method: Two colour flow cytometry using monoclonal antibodies against CD3 and TCRVβ families was used to map TCRVβ usage. T and B clonal cell populations were examined in peripheral blood lymphocytes (PBLs) by PCR and sequencing of TCRβ/TCRγ T cell and IgH FR2/FR3 B cell products. Nine OS patients were investigated and their RAG, RAG2, and Artemis genes were sequenced and compared with results from age matched controls.

Results: All nine OS patients showed absent TCRVβ families; four had predominant TCRVβ families. Six patients had oligoclonal TCR gene rearrangements, including one with oligoclonal TCRGD rearrangements. One child had a functional IGH rearrangement, an observation not previously reported. A RAG gene mutation was identified in only two patients.

Conclusion: In a clinically homogeneous population of OS patients, oligoclonal T cell expansions were seen in six of eight individuals and clonal B cells were found in another. Molecular characterisation identified only two individuals with a deficiency in the recombinase gene RAG1 and none with a deficiency in artemis. This suggests that …

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