G Rotondo Dottore1, L Torregrossa2, G Lanzolla1, S Mariotti3, F Menconi1, P Piaggi4, L Cristofani Mencacci5, C Posarelli6, M N Maglionico6, I Dallan5, M Figus6, M Nardi6, C Marcocci1, F Basolo2, M Marinò7. 1. Department of Clinical and Experimental Medicine, Endocrinology Units, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, 56124, Italy. 2. Department of Surgical, Medical and Molecular Pathology, Pathology Unit, University of Pisa and University Hospital of Pisa, Via Paradisa 2, Pisa, 56124, Italy. 3. Retired. Formerly Department of Medical Sciences and Public Health, University of Cagliari, SS 554 Bivio per Sestu, Monserrato, 09042, Italy. 4. Department of Information Engineering, University of Pisa and University Hospital of Pisa, Via G. Caruso 16, Pisa, 56122, Italy. 5. Department of Surgical, Medical and Molecular PathologyENT Unit I, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, 56124, Italy. 6. Department of Surgical, Medical and Molecular PathologyOphthalmology Unit I, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, 56124, Italy. 7. Department of Clinical and Experimental Medicine, Endocrinology Units, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, 56124, Italy. michele.marino@med.unipi.it.
Abstract
OBJECTIVE: The extent to which mononuclear cells and TSH-receptor autoantibodies (TRAb) contribute to Graves' orbitopathy (GO) is not completely defined. Here we investigated the relationship between the immunohistochemical phenotype of orbital infiltrating cells and GO features in a large number of patients. METHODS: We conducted an observational cohort study in 76 consecutive patients with GO (16 men and 60 women) who underwent orbital decompression over a period of 18 consecutive months. An ophthalmological evaluation was performed in all patients, as well as immunohistochemistry for CD3, CD4, CD8, CD56 (T-cell markers), CD25 (T and B-cell marker), CD20, CD19 (B-cell markers), and CD138 (plasmacell marker) in specimens collected at decompressive surgery. RESULTS: Having established cutoff values for each marker, cell infiltrates were found in 60 patients (78.9%; CD3: 39.4%, CD4 55.2%, CD8 50%, CD56: 0%, CD25: 28.9%, CD20: 51.3%, CD19: 25%, CD138: 26.3%). Eleven (14.4%) stained exclusively for CD138 (plasmacells). Patients with CD4-positive mononuclear cells had a significantly greater GO clinical activity score (CAS) (mean difference 1.07, 95% CI - 0.33 to - 1.82, P = 0.004 by univariate, P = 0.05 by multivariate analysis). CAS as well as the remaining GO features were not affected significantly by the mononuclear cell subpopulations in multivariate analyses. CONCLUSIONS: Mononuclear cell infiltrates are present in the majority of GO patients, with a small percentage represented exclusively by plasmacells. CD4 cells exert a major role on GO activity. These findings may represent a further advancement in the comprehension of GO pathogenesis.
OBJECTIVE: The extent to which mononuclear cells and TSH-receptor autoantibodies (TRAb) contribute to Graves' orbitopathy (GO) is not completely defined. Here we investigated the relationship between the immunohistochemical phenotype of orbital infiltrating cells and GO features in a large number of patients. METHODS: We conducted an observational cohort study in 76 consecutive patients with GO (16 men and 60 women) who underwent orbital decompression over a period of 18 consecutive months. An ophthalmological evaluation was performed in all patients, as well as immunohistochemistry for CD3, CD4, CD8, CD56 (T-cell markers), CD25 (T and B-cell marker), CD20, CD19 (B-cell markers), and CD138 (plasmacell marker) in specimens collected at decompressive surgery. RESULTS: Having established cutoff values for each marker, cell infiltrates were found in 60 patients (78.9%; CD3: 39.4%, CD4 55.2%, CD8 50%, CD56: 0%, CD25: 28.9%, CD20: 51.3%, CD19: 25%, CD138: 26.3%). Eleven (14.4%) stained exclusively for CD138 (plasmacells). Patients with CD4-positive mononuclear cells had a significantly greater GO clinical activity score (CAS) (mean difference 1.07, 95% CI - 0.33 to - 1.82, P = 0.004 by univariate, P = 0.05 by multivariate analysis). CAS as well as the remaining GO features were not affected significantly by the mononuclear cell subpopulations in multivariate analyses. CONCLUSIONS: Mononuclear cell infiltrates are present in the majority of GO patients, with a small percentage represented exclusively by plasmacells. CD4 cells exert a major role on GO activity. These findings may represent a further advancement in the comprehension of GO pathogenesis.
Authors: M de Carli; M M D'Elios; S Mariotti; C Marcocci; A Pinchera; M Ricci; S Romagnani; G del Prete Journal: J Clin Endocrinol Metab Date: 1993-11 Impact factor: 5.958
Authors: A Basolo; A M Poma; D Bonuccelli; A Proietti; E Macerola; C Ugolini; L Torregrossa; R Giannini; P Vignali; F Basolo; F Santini; A Toniolo Journal: J Endocrinol Invest Date: 2022-02-15 Impact factor: 4.256