Background/Purpose: Autoimmune diseases, including systemic lupus erythematosus (SLE), juvenile dermatomyositis (JDM), and Autoimmune Encephallitis (AE) arise due to dysregulation of the immune system and a breakdown in tolerance to self-antigen. The immunological profile in autoimmune diseases, and within clinically heterogeneous diseases such as SLE, are not well characterized in pediatric populations (Van Nieuwenhove, 2019). A better understanding of changes in the immunological profile during autoimmune pathogenesis may provide insight into disease pathophysiology, enable more precise disease classification and improved diagnosis, and suggest important targets for novel therapies. Rituximab is an anti-CD20 cytolytic antibody that is approved in the US and EU for treatment of lymphoma and vasculitis, but widely used in pediatric patients with a variety of autoimmune diseases (including SLE, JDM, AE, NMO) to selectively deplete B cells. Recent studies suggest that rituximab is also associated with perturbations in non-target lymphocytes that correlate with clinical outcomes. Data on the reconstitution of CD20+ B cells after rituximab treatment is lacking, and there is no consensus on optimal dosing schedule or monitoring of lymphocytes during rituximab treatment. Therefore, this study aimed to characterize target B-cell reconstitution in pediatric autoimmune disease,  as well as to examine the off-target effects of rituximab in pediatric patients.

Methods: A retrospective review of patients aged 5-29 years of age treated with rituximab at a large tertiary hospital between 2014 and 2019 was performed. Peripheral blood lymphocytes including CD3+CD4+, CD3+CD8+, alpha/beta, gamma delta, memory and naive T cells, CD16+CD56+ NK cells, and CD19+ and CD20+ B cells were collected prior to and during rituximab treatment. Statistical analysis was performed using STATA/SE 16.0 (College Station, TX).

Results: 100 patients with autoimmune diagnosis codes, including SLE (n=24), JDM (n=14), and AE/NMO (n=57) who received rituximab were identified. The average number of lymphocyte enumeration panels performed per patient was 3 (range 1-11). Lymphocyte enumeration panels were collected 193 days from prior rituximab infusion (range 5-1696). Preliminary data showed there was no significant difference in CD4:CD8 T cell ratio across diagnoses. Initial results from the analysis of CD20+ B cell reconstitution in patients with SLE, JDM, and AE/NMO will be presented.

Conclusion: There is significant variability in the timing of lymphocyte monitoring during rituximab treatment. Further analysis of CD20+ B cell reconstitution can be used to generate standardized protocols for rituximab dosing interval protocols as well as lymphocyte monitoring interval.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunological-profiles-following-treatment-with-rituximab-in-autoimmune-disease/