POS0266 CELLULAR IMMUNE RESPONSE PERSISTENCE AFTER COVID-19 MRNA VACCINES AMONG PATIENTS WITH RHEUMATOID ARTHRITIS UNDER RITUXIMAB

Abstract

BackgroundHumoral response induced by anti-SARS-CoV-2 mRNA vaccine is significantly lower or even absent in patients with inflammatory rheumatic diseases treated with anti-CD20 therapies such as Rituximab (RTX) than in those treated with cytokine therapies (e.g., anti-TNF or anti-IL6) [1]. However, a specific cellular immune response exists 1 or 2 months after vaccination (2, 3). As cytotoxic T cells are considered as essential components of the antiviral defense arsenal, and since it is not clear when to do booster shots, analysis of thespecific T response over the long term could be a useful decision-making tool.ObjectivesThis study aims to compare the spike-specific T lymphocytes response in a cohort of Rheumatoid Arthritis (RA) patients under RTX or other therapies (csDMARDs, anti-TNF). Our secondary goal was to assess the retention of this response up to 18 months after the last COVID boost (vaccine or infection).MethodsPatients.Our study cohort included 75 consecutive adult patients with ACPA positive RA, followed at the rheumatology department of Sainte Marguerite Hospital (Marseille, France), prospectively enrolled from April 2022 to October 2022. RA patients fulfilled the 2010 ACR/EULAR criteria for RA and had received at least two doses of SARS-COV-2 mRNA vaccine, whether they had or not a history of COVID.Samples.Heparin-anticoagulated single blood sample was collected for each patient to assess CD19+ cell count, IgG level, and SARS-CoV-2 serology. Cellular immune response was assessed by flow cytometry with a previously described procedure [4]. Briefly, 250 µL of whole blood were incubated per condition, including a negative control, Spike peptides from JPT* collection and CEFX peptides (mix of viral peptides) as a positive control. Marker expression was measured with a three-laser 13-color CytoFLEX flow cytometer. T lymphocytes were divided into T4 lymphocytes (LT4) or T8 lymphocytes (LT8) depending on CD8 expression. Finally, CD69, CD154, CD137 and CD107a expressions were monitored to characterize LT4 or LT8 activation.Ethics.All patients gave informed written consent for this study in accordance with Helsinki declaration. Patient data were pseudo-anonymized. Sample collection was approved by the national ethics committee under the number DC-2008-327.ResultsPatient characteristics: 51 RA patients were treated with RTX, 24 were treated with csDMARDs or other bDMARDs.Humoral response against SARS CoV 2: 30/51 (59%) RA RTX patients versus 13/14 (93%) non RTX patients had a humoral immune response (p = 0.024) with a median titer of 130 BAU/mL versus 688 BAU/mL.T cell specific response: LT4 and LT8 Spike-specific responses were defined by the difference of response between Spike peptides from SARS CoV 2 stimulation and no peptides stimulation. The response was divided into quartiles, patients in the upper 3 quartiles were considered to have a specific response. In RA RTX patients, specific LT8 response was shown in 90% of patients versus 42% in non RTX patients (p < 0.0001), and specific LT4 response was shown in 76 % of patients versus 75% in non RTX patients (p = 0.42).Long term T cell specific response(Figure 1). RA patients treated with RTX maintained a specific LT4 and LT8 response against Spike peptides with no decrease up to 18 months after the last SARS-COV-2 boost (vaccine dose or COVID 19 infection).ConclusionSpecific LT4 response against Spike peptides was similar in the RTX treated and non-treated RA patients. This was even stronger for the specific LT8 response. The Spike specific T-cell response was maintained in both groups up to 18 months after the last vaccine dose or COVID infection independently to the specific humoral response. This method of analyzing the specific T response against the Spike protein could be used in personalized medicine to decide when revaccination is necessary in a given patient.