Transient and persistent expansions of large granular lymphocytes (LGL) and NK-associated (NKa) cells: the Yorkshire Leukaemia Group Study

• Published in: British journal of haematology Vol. 83; no. 3; p. 505
• Main Authors: Scott, C S, Richards, S J, Sivakumaran, M, Short, M, Child, J A, Hunt, K M, McEvoy, M, Steed, A J, Balfour, I C, Parapia, L A
• Format: Journal Article
• Language: English
• Published: England 01-03-1993
• Subjects: Adult; Antigens, CD - analysis; Cytoplasmic Granules - pathology; Genotype; Humans; Immunophenotyping; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Leukocyte Count; Lymphocytes - immunology; Lymphocytes - pathology; Lymphocytosis - blood; Lymphocytosis - genetics; Neutrophils - pathology; Time Factors
• ISSN: 0007-1048
• DOI: 10.1111/j.1365-2141.1993.tb04678.x

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 x 10(9)/l) of morphologically-defined large granular lymphocytes (LGL), and/or phenotypically-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 x 10(9)/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.