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Lymphoma

Genotypic evaluation of killer immunoglobulin-like receptors in NK-type lymphoproliferative disease of granular lymphocytes

Leukemia volume 21, pages 1060–1069 (2007)Cite this article

Abstract

Using polymerase chain reaction (PCR)-based sequence-specific primers, the killer immunoglobulin-like receptor (KIR) genotypes of 35 patients with natural killer (NK)-type lymphoproliferative disease of granular lymphocytes and of 50 normal subjects were investigated to evaluate whether genes coding for activating KIRs were more frequently detected in patients with NK-lymphoproliferative disease of granular lymphocytes (LDGL). Genotype frequency indicated that the most frequently found gene content was eight genes in controls and 14 in patients (P<0.05). The KIR genotype analysis revealed that patient and, surprisingly, control KIR genotypes preferentially consisted of type B haplotypes characterized by the presence of multiple-activating KIRs. Evidence was also provided that the same KIR genotype was shared by a variable number of patients. Interestingly, the recurrent genotypes observed in the patient group were not found in controls. Concerning inhibitory genes, KIR2DL5a and 2DL5b were more frequently detected in patients than in controls (P<0.01), likely representing a discrete feature of the genetic repertoire of the patients. KIR gene repertoire analysis in patients suggests that the susceptibility to NK-LDGL might be related to the presence of activating KIR genes and supports the concept that these receptors may be involved in the priming of granular lymphocytes (GL) proliferation. Population analysis might disclose a genetic background predisposing to this disease.

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Acknowledgements

We thank Drs D Senitzer and JY Sun (Duarte, CA, USA) for providing synthetic oligonucleotides for multiplex PCR-SSP, Professor A Moretta for giving mAbs for KIRs cytofluorimetric analysis and the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA, Rome, Italy) who supplied us with epidemiological data about LDGL disease in the Italian population. We are grateful to Dr Martin Donach for editing this paper. This study was supported in part by the Associazione Italiana per la Ricerca sul Cancro (AIRC), the Ministero dell'Istruzione dell'Università e della Ricerca (MIUR) and the Consiglio Nazionale delle Ricerche (CNR), the Fondo per gli Investimenti della Ricerca di Base (FIRB), the Fondo Regionale Regione Veneto, and grants from IOV.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Padua University School of Medicine, Hematology and Clinical Immunology Branch, Padova, Italy

    E Scquizzato, A Teramo, M Miorin, M Facco, F Piazza, L Trentin, C Agostini, R Zambello & G Semenzato

  2. V Medical Clinic, University of Padua, Padova, Italy

    F Noventa

  3. Venetian Institute of Molecular Medicine (VIMM), Centro Interdipartimentale di Ricerca per lo studio di segnali cellulari, Padova, Italy

    E Scquizzato, A Teramo, M Facco, F Piazza, L Trentin, C Agostini, R Zambello & G Semenzato

  4. Istituto Oncologico Veneto (IOV), Padova, Italy

    E Scquizzato, A Teramo, M Miorin, M Facco, F Piazza, L Trentin, C Agostini, R Zambello & G Semenzato

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Correspondence to G Semenzato.

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Scquizzato, E., Teramo, A., Miorin, M. et al. Genotypic evaluation of killer immunoglobulin-like receptors in NK-type lymphoproliferative disease of granular lymphocytes. Leukemia 21, 1060–1069 (2007). https://doi.org/10.1038/sj.leu.2404634

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