TY - JOUR
T1 - Scleritis and multiple systemic autoimmune manifestations in chronic natural killer cell lymphocytosis associated with elevated TCRα/ β+CD3+CD4-CD8- double-negative T cells
AU - Yeh, S.
AU - Li, Z.
AU - Sen, H. N.
AU - Lim, W. K.
AU - Gill, F.
AU - Perkins, K.
AU - Rao, V. K.
AU - Nussenblatt, R. B.
PY - 2010/6
Y1 - 2010/6
N2 - Background/aims: 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 g, tumor necrosis factor α, IL1, monocyte chemotactic protein 1) and immunoregulatory cytokines (IL4, IL5 and IL10). An abnormal elevation of TCRα/β+ CD3+CD4 -CD8- T cells suggestive of autoimmune lymphoproliferative syndrome was observed; however, apoptosis dysfunction was not found. Conclusion: 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.
AB - Background/aims: 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 g, tumor necrosis factor α, IL1, monocyte chemotactic protein 1) and immunoregulatory cytokines (IL4, IL5 and IL10). An abnormal elevation of TCRα/β+ CD3+CD4 -CD8- T cells suggestive of autoimmune lymphoproliferative syndrome was observed; however, apoptosis dysfunction was not found. Conclusion: 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.
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U2 - 10.1136/bjo.2009.171264
DO - 10.1136/bjo.2009.171264
M3 - Article
C2 - 20508050
AN - SCOPUS:77953762020
SN - 0007-1161
VL - 94
SP - 748
EP - 752
JO - British Journal of Ophthalmology
JF - British Journal of Ophthalmology
IS - 6
ER -