ETA2024 Poster Presentations TED (10 abstracts)
1Graves Orbitopathy Center, Fondazione Irccs Cà Granda, Ospedale Maggiore Policlinico, University of Milan, Endocrinology, Milan, Italy; 2University of Milan, Clinical Sciences and Community Health; Endocrinology; Graves Orbitopathy Centre, Clinical Sciences and Community Health, Milan, Italy; 3University of Milan, Italy, Department of Clinical Sciences and Community Health, Milan, Italy; 4National Institute of Molecular Genetics (Ingm), Milan, Italy; 5University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy; 6Graves Orbitopathy Centre, Endocrine; Fondazione Irccs Ca Granda, University of Milan, University of Milan, Milan, Italy; 7University of Milan, Italy, Department of Clinical Sciences and Community Health; 8Graves Orbitopathy Center, Endocrinology Unit, Fondazione Irccs Cà Granda Ospedale Maggiore Policlinico, Milan, Italy, Italy; 9Ophthalmology, Fondazione Irccs Cà Granda, Ospedale Maggiore Policlinico, Graves Orbitopathy Center, Endocrinology Unit, Fondazione Irccs Cà Granda Ospedale Maggiore Policlinico, Milan, Italy, Italy; 10University of Milan, Fondazione Irccs Ca Granda, Clinical Sciences and Community Health, Milano, Italy; 11National Institute of Molecular Genetics (Ingm), Milan, Italy, Italy; 12Graves Orbitopathy Centre, Endocrine, Fondazione Irccs Ca Granda, University of Milan, Milan, Italy
Introduction: Rituximab is an anti-CD20 monoclonal antibody used as second-line treatment for patients with moderate-to-severe and active Thyroid Eye Disease (TED) and resistant to i.v. Methylprednisolone (ivMP). Rituximab induces B-cells depletion in the peripheral blood and in target organs of patients with TED. We report on a case of a patient with active TED successfully treated with two doses of Rituximab 500 mg i.v. after immunophenotypic characterization by flow cytometry of lymphocytes derived from blood and ultrasound-guided-fine-needle aspiration (US-FNA) of thyroid and neck lymph nodes (LNs). Analysis and immunophenotyping of retro-orbital tissue were also performed after decompression surgery.
Case report: A 55-year-old man with a history of TED, presented with activation of the right eye in January 2021 (CAS 4/10) that was treated with ivMP, resulting in disease inactivation (CAS 0/10), with residual marked proptosis. After 18 months he presented with active TED in the left eye (CAS 5/10). We performed a first immunophenotypic analysis which showed elevated count of CD19+ B-cells in the blood, thyroid and LNs. We then decided to treat him with a dose of Rituximab 500 mg i.v\. After 4 weeks, we detected no CD19+ B-cells in the blood and thyroid while, unexpectedly, we found a certain degree of residual infiltration in LNs. Treatment appeared to be ineffective (CAS 6/10). Based on the immunophenotype findings, we decided to administer a second dose of Rituximab 500 mg i.v., which led to complete and lasting inactivation of TED (CAS 0/10) and total B-cells depletion also in LNs. We also observed a progressive reduction of follicular T helper lymphocytes (Tfh) and Germinal-Center (GC) Tfh in LNs of the patient. After treatment CD4+ T lymphocytes showed a reduction of CD69 and CD40L expression, both in LNs and blood. Tissue obtained from orbital decompression 6 months after Rituximab therapy was characterized by B-cells infiltration with a reduction of naive B-cells and an increase of memory B-cells, when compared to orbital tissue from chronic TED.
Conclusions: We have shown the feasibility of personalized therapy in a patient with TED otherwise resistant to ivMP. Effectiveness of Rituximab was associated with reduction of B-cells in the blood, thyroid and cervical LNs. Our results also show that Rituximab not only predictably depletes B-cells, but also influences T-cells, with changes of subsets (Tfh and GC-Tfh cells) and modifications of the activation/co-stimulation status (CD40L and CD69 expression), which suggests a more complex mechanism of action.