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. 1994 May;47(5):399–404. doi: 10.1136/jcp.47.5.399

Clonality of CD3 negative large granular lymphocyte proliferations determined by PCR based X-inactivation studies.

A Kelly 1, S J Richards 1, M Sivakumaran 1, C Shiach 1, A D Stewart 1, B E Roberts 1, C S Scott 1
PMCID: PMC502013  PMID: 8027391

Abstract

AIMS--To examine persistent CD3-large granular lymphocytosis (LGL) cases for clonality, both by lineage specific (T cell receptor) and lineage independent (X-inactivation) molecular methods; and to find out whether X-inactivation studies are more appropriate than gene rearrangement studies for this subset of LGL disorders. METHODS--Patients were selected who had LGL of more than six months' duration and identified as CD3- by immunophenotyping. T cell receptor studies and, where possible, X-inactivation studies of the phosphoglycerate kinase (PGK) gene were carried out. Analysis of subpopulations was carried out on cases heterozygous for PGK by the use of a polymerase chain reaction (PCR) method for X-inactivation. RESULTS--Of 17 CD3- LGL cases studied, all were found to be germline for beta, gamma, and delta T cell receptor studies, and immunoglobulin heavy chain genes. However, six of these were analysed by X-inactivation of the PGK gene and two cases gave clonal band patterns but only within the CD3- subpopulation. CONCLUSIONS--Clonal analysis by the lineage independent method of X-inactivation allows clonal expansion undetected by T and B cell specific markers to be identified. It is therefore a more appropriate method for the analysis of CD3- LGL. This has implications for diagnosis in CD3- LGL disorders.

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