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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+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 patient9s disease. Further studies regarding NK cell dysfunction and ocular autoimmunity are needed.

Studies of the increased or decreased risk of specific physical diseases in patients with schizophrenia and affective disorder are reviewed. Existing data suggest further examination of the following relationships: (1) the presence in schizophrenics of increased incidence of gastrointestinal cancer and of cardiovascular and infectious diseases, and of decreased incidence of lung cancer and rheumatoid arthritis; and (2) the increased incidence of circulatory, respiratory, and atopic diseases, and of diabetes mellitus among patients with major affective disorder. A majority of the studies reviewed failed to meet methodologic standards necessary to provide conclusive evidence. An ongoing research project which generally meets these standards, the Oxford Record Linkage Study, is described.

Sanfilippo syndrome type A or mucopolysaccharidosis IIIA (MPS IIIA) results from the deficiency of the enzyme heparan N-sulfatase (NS, EC 3.10.1.1), required for the degradation of heparan sulfate. Molecular defects of 24 Italian MPS IIIA patients were recently reported by our group. We report here two novel mutations: 1040insT and Q365X and the expression studies on 15 of the identified defects. Transient expression of COS cells by cDNA mutagenized to correspond to heparan N-sulfatase mutations Y40N, A44T, 166delG, G122R, P128L, L146P, R150Q, D179N, R182C, R206P, P227R, 1040insT, 1093insG, E369K, R377C did not yield active enzyme, demonstrating the deleterious nature of the mutations. Western blot analysis and metabolic labeling experiments revealed, for cells transfected with wild-type enzyme, a precursor 62-kDa form and a mature 56-kDa form. Western blot resulted, for 11 mutations, in the presence of both forms, indicating a normal maturation of the mutant enzyme. Western blot, metabolic labeling and immunofluorescence experiments suggested, for mutations 166delG, L146P, 1040insT and 1093insG, an increased degradation of the mutant enzymes. (C) 2000 Published by Elsevier Science B.V.