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Peer-reviewedCC BY-NC-ND 4.0In Vivo

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

11 affiliations
  1. 1School of Medicine, National Defense Medical University, Taipei, Taiwan, R.O.C.
  2. 2Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan, R.O.C.
  3. 3Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark
  4. 4The Finsen Laboratory, Rigshospitalet/National University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  5. 5School of Pharmacy, National Defense Medical University, Taipei, Taiwan, R.O.C.
  6. 6Graduate Institute of Life Sciences, National Defense Medical University, Taipei, Taiwan, R.O.C.
  7. 7Department of Internal Medicine, Linkou Chang-Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
  8. 8Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
  9. 9Cancer Center, Hualien Tzu-Chi Hospital, Hualien, Taiwan, R.O.C.
  10. 10Department of Engineering Medicine, Shizuoka Center for Molecular Intelligence, Hamamatsu, Shizuoka, Japan
  11. 11Rheumatology/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan, R.O.C.

Abstract

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.

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BibTeX
@article{hung2026vivo,
  title = {{In Vivo Dynamics of Immunoregulatory Lymphocyte Reconstitution: A Seven-year Longitudinal Study of Sustained Remission in Class IV Lupus Nephritis Following Rituximab Therapy}},
  author = {SHAU-JIE HUNG and JENG-WEI LU and YI-JUNG HO and SHAN-WEN LUI and TING-YU HSIEH and WUN-LONG JHENG and FENG-CHENG LIU},
  journal = {In Vivo},
  year = {2026},
  month = oct,
  doi = {10.21873/invivo.14532},
  url = {https://doi.org/10.21873/invivo.14532},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - In Vivo Dynamics of Immunoregulatory Lymphocyte Reconstitution: A Seven-year Longitudinal Study of Sustained Remission in Class IV Lupus Nephritis Following Rituximab Therapy
AU  - SHAU-JIE HUNG
AU  - JENG-WEI LU
AU  - YI-JUNG HO
AU  - SHAN-WEN LUI
AU  - TING-YU HSIEH
AU  - WUN-LONG JHENG
AU  - FENG-CHENG LIU
PY  - 2026
DA  - 2026/10/29
JO  - In Vivo
DO  - 10.21873/invivo.14532
UR  - https://doi.org/10.21873/invivo.14532
AB  - 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.
SN  - 0258-851X
SN  - 1791-7549
ER  -