Colin Scott1, Stephen J. Richards1, Muttuswamy Sivakumaran2, Michael Short2, J. A. Child3, K M Hunt4, Marian T. McEvoy5, A J Steed6, Ian Balfour7, L A Parapia8, B. A. McVerry9, A. G. Bynoe10, M. C. Galvin11, D. R. Norfolk3, B. E. Roberts3
1Yorkshire Leukaemia Diagnostic Unit, Cookridge Hospital
2Molecular Haematology Unit, Leeds General Infirmary, and Departments of Haematology
3Leeds General Infirmary
4St Lukes Hospital, Bradford
5Harrogate General Hospital
6Halifax General Hospital
7Scarborough General Hospital.
8Bradford Royal infirmary
9St James' Hospital, Leeds
10Wharfedale General Hospital
11Pinderfields Hospital
Tóm tắt
Summary. A survey of 870 different adult blood samples (primarily from patients with non‐haematological disorders) found that 269 (31%) had increased proportions (>25%) and/or absolute numbers (>1.0 × 109/l) of morphologically‐defined large granular lymphocytes (LGL), and/or pheno‐typically‐defined NK‐associated (NKa) cells. Of these, 112 were re‐analysed at least 6 months after initial presentation and were classified as‘persistent’(92/112) or ‘transient’(20/112) according to whether or not the original abnormality was still present. Lymphocyte counts in most patients with persistent abnormalities were within normal limits (18/92) or slightly increased (68/92), with only six having a lymphocytosis exceeding 10.0 × 109/l. With the exception of five persistent LGL expansions in which the granular lymphocytes did not express NKa determinants (designated LGL+NKa‐), the remaining 87 cases could be phenotypically grouped according to their primary abnormality as CD8+NKa+ (n = 33), CD4+ NKa+ (n=14), CD8dim+NKa+ (n=7) or CD8−NKa+ (n=33). TCR genotypic studies in 58 patients showed that the 16 patients with rearranged TCR components were restricted to the CD8+NKa+ group and that, in most of these, the CD8+ fraction showed abnormal relative CD16/CD56 expression. Persistent neutropenia (n=15) also appeared to be associated with primary abnormalities of CD8+NKa+ cells (12/15). with 10 of these additionally showing rearranged TCR genes. In contrast, persistently increased CD8dim+NKa+ and CD8–NKa+ components did not appear to phenotypically differ from their corresponding ‘counterparts’in normal bloods or in patients with transient LGL/NKa+ abnormalities. This survey has therefore established that persistent LGL/NKa+ abnormalities are considerably more common than suggested in published work, that a high proportion of patients with expanded CD8+NKa+ components, with quite diverse clinical histories, show evidence of clonal lymphoid populations, and that the clonal nature of such disorders appears to be associated with abnormal NKa phenotypic patterns.
