Clinical Research Article | Published:

Rituximab modulates T- and B-lymphocyte subsets and urinary CD80 excretion in patients with steroid-dependent nephrotic syndrome

Pediatric Research (2018) | Download Citation

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Abstract

Background

Rituximab, a monoclonal antibody targeting B lymphocytes, effectively sustains remission in steroid-dependent nephrotic syndrome (SDNS). We studied its effects on lymphocyte subsets and urinary CD80 excretion (uCD80) in patients with SDNS.

Methods

Blood and urine samples were collected from 18 SDNS patients before rituximab, and after 1 month and 1 year or at first relapse. T and B lymphocytes and uCD80 were determined by flow cytometry and ELISA, respectively.

Results

Treatment was associated with reduction in counts of Th17, Th2, and memory T cells, and increased T-regulatory (Treg) cells. The Th17/Treg ratio declined from baseline (median 0.6) to 1 month (0.2, P = 0.006) and increased during relapse (0.3, P = 0.016). Ratios of Th1/Th2 cells at baseline, 1 month after rituximab, and during relapse were 7.7, 14.0 (P = 0.0102), and 8.7, respectively. uCD80 decreased 1 month following rituximab (45.5 vs. 23.0 ng/g creatinine; P = 0.0039). B lymphocytes recovered earlier in relapsers (60.0 vs.183.0 days; P < 0.001). Memory B cells were higher during relapse than remission (29.7 vs.18.0 cells/µL; P = 0.029).

Conclusion

Rituximab-induced sustained remission and B-cell depletion was associated with reduced numbers of Th17 and Th2 lymphocytes, and increased Treg cells; these changes reversed during relapses. Recovery of B cells and memory B cells predicted the occurrence of a relapse.

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Acknowledgements

D.B., A.S., and A.B. conceived the study. D.B. performed all the experiments. A.B., A.S., and P.H. contributed clinical samples. D.B. and A.B. wrote and edited the manuscript; A.B. supervised the project. All authors read and approved the manuscript. This work was supported in part by grants from the Indian Council of Medical Research (5/4/7-12/1-NCD-II) and the British Council (UKIERI-TRP-2012/13-001) to A.B.

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Affiliations

  1. Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India

    • Divya Bhatia
    • , Aditi Sinha
    • , Pankaj Hari
    • , Savita Saini
    • , Mamta Puraswani
    • , Himanshi Saini
    •  & Arvind Bagga
  2. Pediatric Biology Center, Translational Health Science & Technology Institute, Faridabad, India

    • Shailaja Sopory
  3. Department of Transplant Immunology & Immunogenetics, All India Institute of Medical Sciences, New Delhi, India

    • Dipendra K Mitra

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The authors declare no competing interests.

Corresponding author

Correspondence to Arvind Bagga.

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DOI

https://doi.org/10.1038/s41390-018-0088-7

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