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J J Blizzard

Publications and source records attributed to J J Blizzard.

7 recordsLinked to original sources

Lymphocyte subpopulations in Graves' ophthalmopathy.

We assessed the percentages of T-lymphocyte subsets, B lymphocytes, monocytes, and granulocytes in the mononuclear cell preparations of euthyroid patients with minimal and severe Graves' ophthalmopathy. Patients with active Werner class 4-5 and class 6 ophthalmopathy had statistically significant elevations of suppressor/cytotoxic T8+ lymphocytes. During successful corticosteroid therapy, the number of T8+ lymphocytes returned to the normal range. Mirroring these results, the T4/T8 ratio was initially depressed in patients with class 4-5 ophthalmopathy and increased during therapy. Our previous observations noted a decreased number of rosette-forming T lymphocytes in patients with severe ophthalmopathy. In this study, however, there were normal percentages of T3+ and T11+ lymphocytes, suggesting that the T lymphocytes are present in peripheral blood but they cannot form rosettes. There was a slight reduction of the percentage of the T11+ (erythrocyte receptor) lymphocytes in the patients with class 4-5 ophthalmopathy; however, it was not statistically significant. No significant differences were evident in any of the other T-lymphocyte subsets, B lymphocytes, monocytes, or granulocytes studied. We conclude that Graves' ophthalmopathy is characterized by a surface membrane defect associated with increased percentages of suppressor/cytotoxic T8+ lymphocytes. Successful corticosteroid therapy reverses these findings.

Adult

Association of HLA antigen BW35 with severe Graves' ophthalmopathy.

Human leukocyte antigens (HLA) in patients with Graves' disease were investigated according to the ophthalmic classification system of the American Thyroid Association. All prior HLA studies of Graves' disease have disregarded the patients' specific ophthalmic manifestations. Examination of 18 A and 34 B loci antigens disclosed an increased frequency (corrected P = 0.002, relative risk = 13.1) of HLA-BW35 in patients improving with oral corticosteroids who have severe extraocular muscle and orbital inflammation (class 4-5) when compared to a geographically and racially matched control population. No statistically significant associations were found when patients without ophthalmic manifestations or with other categories of Graves' ophthalmopathy were compared to controls. The association of severe Graves' ophthalmopathy with HLA-BW35 may provide immunologic evidence to explain both the unpredictable association of the orbital and thyroid disturbances of Graves' disease as well as the unpredictable response of the orbital inflammation to oral corticosteroids.

Adrenal Cortex Hormones

The clinical immunology of Graves' ophthalmopathy.

Graves' ophthalmopathy is frequently a diagnostic and therapeutic dilemma for practicing ophthalmologists. We have reviewed the clinical immunology of this disorder with regard to clinical manifestations, humoral immunity, and cellular immunity. Special emphasis with applicable clinical and laboratory data is given to the hypothesis that Graves' thyrotoxicosis and ophthalmopathy may be frequently associated diseases rather than disorders caused by a common pathogenetic mechanism. Dysthyroidism may be the substrate for the development of the ophthalmopathy, but the two disorders probably are caused by different immunopathogenetic mechanisms.

Autoimmune Diseases

Graves' ophthalmopathy--immunologic parameters related to corticosteroid therapy.

Patients with severe Graves' ophthalmopathy may or may not improve with systemic corticosteroids. In an attempt to find immunologic distinctions to correspond with this clinical phenomenon, we have evaluated various parameters in corticosteroid-responsive and corticosteroid-resistant individuals. Percentages and absolute numbers of thymus-derived active and total rosette-forming cells (A-RFC and T-RFC) underwent statistically significant (p < 0.001) increases during successful prednisone therapy in 17 patients . B lymphocytes and complement receptor mononuclear cells did not significantly change with steroid therapy. In the second group, five patients therapeutically resistant to corticosteroids presented with elevated A-RFC and normal T-RFC. When treated with oral prednisone, these patients' A-RFC decreased (p < 0.001), and the T-RFC were unchanged. Corticosteroids increased the lymphoblast transformation response to phytohemagglutinin (PHA) of a steroid-responsive patient, whereas steroids decreased the PHA lymphoblast transformation response of a corticosteroid-resistant patient. A disease activity index to correlate the clinical and immunologic data has been devised. The findings may allow the clinician to predict which patients with Graves' ophthalmopathy are likely to benefit corticosteroid therapy and which patients may be managed better by other methods.

Adult

E-rosette formation in Graves' ophthalmopathy.

We investigated the lymphocyte characteristics of 77 Graves' disease patients with and without infiltrative ophthalmopathy. Thirteen patients with infiltrative ophthalmopathy without prior antithyroid therapy and 20 euthyroid patients with progressive ophthalmopathy demonstrated decreased percentages of active and total erythrocyte rosette-forming lymphocytes compared to thyrotoxic patients without eye disease and to a control population (p less than 0.001). There was no significant difference in rosette-forming cells between untreated thyrotoxic and treated euthyroid patients with ophthalmopathy. No lymphocytotoxic antibodies or rosette inhibitory factor was present in the sera of patients with infiltrative ophthalmopathy. Untreated and treated patients with lid retraction and mild proptosis without extraocular muscle disease had decreased active rosette-forming cells (p less than 0.001) but normal total rosette-forming cells. Five patients with infiltrative ophthalmopathy who failed to improve with systemic corticosteroids demonstrated elevated active but normal total rosette-forming cells. Differences in rosette formation between ophthalmic and nonophthalmic Graves' disease may represent an associated cell-mediated abnormality that may explain why control of the thyrotoxic state need not correlate with the ophthalmic manifestations of the disorder.

Adult