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Scleritis and multiple systemic autoimmune manifestations in chronic natural killer cell lymphocytosis associated with elevated TCRα/β+CD3+CD4CD8 double-negative T cells
  1. S Yeh1,
  2. Z Li1,
  3. H N Sen1,
  4. W-K Lim1,
  5. F Gill2,
  6. K Perkins3,
  7. V K Rao3,
  8. R B Nussenblatt1
  1. 1Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA
  2. 2Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
  3. 3National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to Robert B Nussenblatt, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Building 10, 10N112, 10 Center Drive, Bethesda, MD 20892, USA


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 γ, tumor necrosis factor α, IL1, monocyte chemotactic protein 1) and immunoregulatory cytokines (IL4, IL5 and IL10). An abnormal elevation of TCRα/β+ CD3+CD4CD8 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.

  • scleritis
  • thyroiditis
  • vitiligo
  • natural killer cell lymphocytosis
  • episcleritis
  • keratoconjunctivitis sicca
  • double-negative T cells
  • autoimmune lymphoproliferative syndrome

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  • Funding This research is supported by the Intramural Research Program of the National Eye Institute, National Institutes of Health and the National Institute for Allergy and Infectious Disease, National Institutes of Health. Dr Steven Yeh has received support from the Heed Ophthalmic Foundation. Other Funders: NIH.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the National Institutes of Health Institutional Review Board (Bethesda, Maryland, USA).

  • Provenance and peer review Not commissioned; externally peer reviewed.