Emergence of long-lived autoreactive plasma cells in the spleen of primary warm auto-immune hemolytic anemia patients treated with rituximab

A reservoir of rituximab-resistant splenic memory B cells contributes to relapses after B-cell depletion therapy

“…Analysis of the molecular program of these cells will probably provide a part of the answer. We can speculate that RTX, by modifying the microenvironment, enable the emergence of a particular transcriptional program in memory B cells favoring their survival, as previously described for LLPC (Mahévas et al, , 2015Thai et al, 2018).…”

“…Because analysis of secondary lymphoid organs after RTX administration is limited in humans, it remains to be demonstrated whether our findings can be generalized to other autoimmune diseases where RTX is effective. However, as mentioned before, RTX-resistant B cell populations mainly composed of memory B cells have been described in several auto-immunes diseases including RA (Ramwadhdoebe et al, 2019) and AIHA (Mahévas et al, 2015), as well as after preventive treatments of humoral graft rejection (Kamburova et al, 2013;Ramos et al, 2007;Wallin et al, 2014), suggesting that persistence of autoreactive clones is not limited to ITP.…”

Emerging Role of the Spleen in the Pharmacokinetics of Monoclonal Antibodies, Nanoparticles and Exosomes

“…This effect could account for therapeutic effects of this monoclonal antibody both as an antineoplastic drug in splenic localization of B-cell neoplasms [55,56] and as an immunosuppressive agent in organ transplantation recipients [57,58], as well as in patients with autoimmune diseases, such as autoimmune thrombocytopenic purpura and systemic lupus erythematosus [59,60,61,62,63]. The relevance of rituximab distribution in the spleen for its pharmacological effect as an immunosuppressant agent is highlighted by the evidence that long-lived CD20 + plasma cells have been identified in the spleen of patients with autoimmune thrombocytopenic purpura or with primary warm auto-immune hemolytic anemia that are resistant to this monoclonal antibody [64,65]. This suggests that when rituximab does not deplete plasma cells in the spleen, it is therapeutically ineffective.…”

The value of rituximab treatment in primary Sjögren's syndrome

“…In contrast to the B cell-associated cytokines mentioned above, serum BAFF levels increase after B cell depletion therapy, likely due to unavailability of BAFF receptors as a consequence of the absence of B cells [22]. This rise in BAFF levels may be unfavorable for the patient due to enhanced survival of autoreactive B cell clones and skewing of newly formed B cells towards an autoreactive phenotype [23,24]. Therefore, the efficacy of therapy combining B cell depletion and BAFF-blockade is currently under investigation (NCT02631538).…”