Scleritis and multiple systemic autoimmune manifestations in chronic natural killer cell lymphocytosis associated with elevated TCRalpha/beta+CD3+CD4-CD8- double-negative T cells.
OBJECTIVE
Chronic natural killer lymphocytosis (CNKL) has been associated with systemic autoimmunity; however, its association with scleritis or ocular autoimmunity has not been characterised. The natural killer (NK) cell function and immunophenotype of a patient with CNKL who developed bilateral scleritis and multiple systemic autoimmune findings were evaluated.


METHODS
The ophthalmic records of a patient with CNKL and scleritis were reviewed over a 6-year period. Flow cytometry was performed to evaluate T cell, NK and B cell populations. NK cellular functions (ie, NK cytotoxicity and cytokine/chemokine production following interleukin 2 (IL2) stimulation) were evaluated.


RESULTS
A 56-year-old woman with vitiligo, psoriatic arthritis, thyroiditis, erythema nodosum, bilateral anterior scleritis and Sjogren syndrome was managed with multiple immunosuppressive medications, including prednisone, mycophenolate mofetil and methotrexate. Flow cytometry showed a persistent elevation of CD56(+)CD3(-) NK cells greater than 40%, which was consistent with CNKL. NK cell cytotoxicity assay identified a deficiency of K562 cell lysis in the patient (1.46 mean-fold greater in control vs patient). NK cytokine/chemokine production following IL2 stimulation was also deficient (2.5-32.5-fold greater in control). Cytokines/chemokines assessed included pro-inflammatory (interferon gamma, tumor necrosis factor alpha, IL1, monocyte chemotactic protein 1) and immunoregulatory cytokines (IL4, IL5 and IL10). An abnormal elevation of TCRalpha/beta(+) CD3(+)CD4(-)CD8(-) T cells suggestive of autoimmune lymphoproliferative syndrome was observed; however, apoptosis dysfunction was not found.


CONCLUSIONS
The association of increased but dysfunctional NK cells in the context of multiple systemic and ocular manifestations suggests a role of NK cells in the pathogenesis of our patient's disease. Further studies regarding NK cell dysfunction and ocular autoimmunity are needed.
Yeh
S
S
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Li
Z
Z
Sen
H N
HN
Lim
W-K
WK
Gill
F
F
Perkins
K
K
Rao
V K
VK
Nussenblatt
R B
RB
D001327:Autoimmune Diseases / Q000276:immunology*; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008218:Lymphocytosis / Q000276:immunology*; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D015423:Scleritis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016207:Cytokines; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta