Transient and persistent expansions of large granular lymphocytes (LGL) and NK-associated (NKa) cells: the Yorkshire Leukaemia Group Study.
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.
Scott
C S
CS
Yorkshire Leukaemia Diagnostic Unit, Cookridge Hospital, Leeds.
Richards
S J
SJ
Sivakumaran
M
M
Short
M
M
Child
J A
JA
Hunt
K M
KM
McEvoy
M
M
Steed
A J
AJ
Balfour
I C
IC
Parapia
L A
LA
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D003594:Cytoplasmic Granules / Q000473:pathology*; D005838:Genotype; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology*; D007958:Leukocyte Count; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology*; D008218:Lymphocytosis / Q000097:blood* / Q000235:genetics; D009504:Neutrophils / Q000473:pathology; D013997:Time Factors
D015703:Antigens, CD