Scleritis and multiple systemic autoimmune manifestations in chronic natural killer cell lymphocytosis associated with elevated TCR / +CD3+CD4-CD8- double-negative T cells

Abstract

Background/Aims Chronic natural killer lymphocytosis (CNKL) has been associated with systemic autoimmunity, but its association with scleritis or ocular autoimmunity has not been characterized. We evaluated the natural kill cell (NK) function and immunophenotype of a patient with CNKL who developed bilateral scleritis and multiple systemic autoimmune findings. 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 (i.e. NK cytotoxicity and cytokine/chemokine production following IL-2 stimulation) were evaluated. Results A 56-year-old female 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 IL-2 stimulation was also deficient (2.5–32.5 fold greater in control). Cytokines/chemokines assessed included pro-inflammatory (IFN-γ, TNF-α, IL-1, MCP-1) and immunoregulatory cytokines (IL-4, IL-5 and IL-10). An abnormal elevation of TCRα/β+ CD3+CD4−CD8− T-cells suggestive of autoimmune lymphoproliferative syndrome was observed but 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.

How I treat autoimmune lymphoproliferative syndrome

“…In contrast, elevation of TCR␣␤ ϩ DNT cells Ͼ 3% of the total lymphocytes (or Ͼ 5% of T lymphocytes) is seldom seen in any conditions other than ALPS. 37,38 One of the primary additional criteria is an abnormal lymphocyte apoptosis assay. However, it is no longer considered essential for the diagnosis of ALPS, as patients with both somatic FAS mutations and germline FASL mutations can present with normal in vitro FAS-induced apoptosis assays.…”

Autoimmune Lymphoproliferative Syndrome (ALPS): A Case Report

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Immunopathological Analysis of a Mouse Model of Arthritis-Associated Scleritis and Implications for Molecular Targeted Therapy for Severe Scleritis

“…Systemic inflammatory diseases associated with posterior scleritis include rheumatoid arthritis, anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis, and thyroiditis [ 21 , 22 , 23 ]. Posterior scleritis with visual loss requires urgent treatment to avoid permanent visual impairment.…”