Gregoire Martin de Fremont1, Andrada Chiron2, Roman Krzysiek3, Salima Hacein-Bey-Abina2, Xavier Mariette4, Gaetane Nocturne5. 1. Rheumatology, AP-HP, Bicêtre Hospital, Le Kremlin Bicêtre, and Université Paris-Saclay, France. 2. Clinical Immunology Laboratory, AP-HP, Bicêtre Hospital, Le Kremlin Bicêtre, and UTCBS, CNRS UMR 8258, INSERM U1267, Faculté de Pharmacie de Paris, Université de Paris, France. 3. Université Paris-Saclay; Clinical Immunology Laboratory, AP-HP, Bicêtre Hospital, Le Kremlin Bicêtre, and INSERM UMR-996, Clamart, France. 4. Rheumatology, AP-HP, Bicêtre Hospital, Le Kremlin Bicêtre; Université Paris-Saclay, and Centre for Immunology of Viral Infections and Autoimmune Diseases (IMVA), Institut pour la Santé et la Recherche Médicale (INSERM) UMR 1184, Université Paris-Saclay, Le Kremlin-Bicêtre, France. 5. Rheumatology, AP-HP, Bicêtre Hospital, Le Kremlin Bicêtre; Université Paris-Saclay, and Centre for Immunology of Viral Infections and Autoimmune Diseases (IMVA), Institut pour la Santé et la Recherche Médicale (INSERM) UMR 1184, Université Paris-Saclay, Le Kremlin-Bicêtre, France. gaetane.nocturne@aphp.fr.
Abstract
OBJECTIVES: Obinutuzumab (OBZ) is a new humanised type II anti-CD20 monoclonal antibody (mAb) approved in onco-haematology. Its use as an alternative to rituximab (RTX) in case of immunisation in autoimmune diseases has not been fully assessed yet. Here we report the case of a patient suffering from a refractory cryoglobulinaemic vasculitis (CV) associated to Sjögren's syndrome (SS) and treated with OBZ. METHODS: Since the patient was immunised against RTX, she was treated with OBZ at relapse. Three days after the infusion of OBZ, she presented a vasculitis flare. Rheumatoid factor level, complement level and cryoprecipitation were evaluated on consecutive serum samples of the patients and after RTX and OBZ addition in vitro. RESULTS: No evidence for cross-reactivity between anti-RTX Abs and OBZ was found. However, we could observe in vitro that cryoprecipitation was worsened by the simultaneous presence of anti-RTX Abs and RTX. We suggest that the flare of CV after OBZ infusion could be linked to a large release of immune complexes following B cells lysis induced by OBZ. CONCLUSIONS: Based on our report, we think that the use of OBZ needs to be carefully discussed in patients with mixed CV.
OBJECTIVES: Obinutuzumab (OBZ) is a new humanised type II anti-CD20 monoclonal antibody (mAb) approved in onco-haematology. Its use as an alternative to rituximab (RTX) in case of immunisation in autoimmune diseases has not been fully assessed yet. Here we report the case of a patient suffering from a refractory cryoglobulinaemic vasculitis (CV) associated to Sjögren's syndrome (SS) and treated with OBZ. METHODS: Since the patient was immunised against RTX, she was treated with OBZ at relapse. Three days after the infusion of OBZ, she presented a vasculitis flare. Rheumatoid factor level, complement level and cryoprecipitation were evaluated on consecutive serum samples of the patients and after RTX and OBZ addition in vitro. RESULTS: No evidence for cross-reactivity between anti-RTX Abs and OBZ was found. However, we could observe in vitro that cryoprecipitation was worsened by the simultaneous presence of anti-RTX Abs and RTX. We suggest that the flare of CV after OBZ infusion could be linked to a large release of immune complexes following B cells lysis induced by OBZ. CONCLUSIONS: Based on our report, we think that the use of OBZ needs to be carefully discussed in patients with mixed CV.
Authors: Janina Paula T Sy-Go; Charat Thongprayoon; Loren P Herrera Hernandez; Ziad Zoghby; Nelson Leung; Sandhya Manohar Journal: Kidney Int Rep Date: 2021-09-04