In Vivo Dynamics of Immunoregulatory Lymphocyte Reconstitution: A Seven-year Longitudinal Study of Sustained Remission in Class IV Lupus Nephritis Following Rituximab Therapy

Background/Aim: Rituximab (RTX)-induced B-cell depletion is an established treatment for refractory lupus nephritis (LN). However, the in vivo kinetics of B-cell reconstitution and their association with sustained clinical remission remain poorly characterized. Because cluster of differentiation 19-positive (CD19+) B-cell monitoring provides a practical measure of immune reconstitution after RTX therapy, we investigated the longitudinal in vivo immunophenotypic recovery of B-cell subsets in a patient with refractory Class IV LN who achieved durable remission. Case Report: A 20-year-old woman presented in 2019 edema, nephrotic proteinuria (8.1 g/day), hematuria, hypoalbuminemia, anemia, and acute kidney injury. Laboratory investigations revealed an antinuclear antibody (ANA) titer >1:1,280, anti-double-stranded DNA (anti-dsDNA) antibodies of 2,525 IU/mL, and hypocomplementemia. Renal biopsy confirmed Class IV lupus nephritis with diffuse proliferative glomerulonephritis and a full-house immunofluorescence pattern. Treatment with intravenous methylprednisolone, RTX, hydroxychloroquine, and immunosuppressive therapy resulted in complete depletion of CD19+ B cells (46.83% to 0%), accompanied by marked reductions in anti-dsDNA antibody levels and improvement in renal function. During seven years of follow-up, CD19+ B cells gradually reconstituted to approximately 20%; however, sustained clinical remission was maintained, with stable renal function, persistently low anti-dsDNA antibody levels, normalization of complement levels, no renal flare, and progressive decline of Antinuclear antibody (ANA) titers to 1:40 and became undetectable. Conclusion: The case demonstrates a persistent dissociation between peripheral CD19+ B-cell repopulation and renal disease activity in vivo. The findings suggest that the quality of immune reconstitution, rather than the absolute number of CD19+ B cells, may be associated with sustained remission after RTX therapy and support the potential value of longitudinal immunophenotypic monitoring.