Natural killer cell dysfunction in patients with systemic-onset juvenile rheumatoid arthritis and macrophage activation syndrome.
OBJECTIVE
To assess natural killer (NK) and cytotoxic functions in patients with systemic-onset juvenile rheumatoid arthrithis (soJRA) complicated by macrophage activation syndrome (MAS).


METHODS
NK cells (CD56+/TCRalphabeta-), NK T cells (CD56+/TCRalphabeta+) and CD8+ cells were assessed for perforin expression by flow cytometry. NK cytotoxic activity was measured after coincubation of mononuclear cells with an NK-sensitive K562 cell line.


RESULTS
Two major patterns of immunologic abnormalities were detected. Four of 7 patients had decreased NK activity, low NK cell numbers, and mildly increased levels of perforin expression in CD8+ and CD56+ cytotoxic cells. Three remaining patients with MAS, however, had decreased NK activity associated with low levels of perforin expression in all cytotoxic cell populations, a pattern indistinguishable from that in carriers of perforin-deficient familial hemophagocytic lymphohistiocytosis. Remarkably, two of these patients had previous episodes of MAS.


CONCLUSIONS
NK dysfunction is an immunologic abnormality common to both familial hemophagocytic lymphohistiocytosis and MAS of soJRA. The extent of NK cell abnormalities in soJRA needs to be further investigated.
Grom
Alexei A
AA
William S. Rowe Division of Rheumatology, and the Division of Hematology/Oncology, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. groma0@chmcc.org
Villanueva
Joyce
J
Lee
Susan
S
Goldmuntz
Ellen A
EA
Passo
Murray H
MH
Filipovich
Alexandra
A
D000293:Adolescent; D001171:Arthritis, Juvenile / Q000276:immunology*; D019002:CD56 Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D004252:DNA Mutational Analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008262:Macrophage Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013577:Syndrome; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology
D019002:CD56 Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin