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Kidney Week

Abstract: SA-PO831

Type 2 Innate Lymphoid Cells Are Activated in Steroid-Resistant Nephrotic Syndrome

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Lu, Liangjian, Khoo Teck Puat-National University Children’s Medical Institute, National University Health System, Singapore, Singapore
  • Chan, Chang-Yien, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
  • Zhang, Yaochun, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
  • Teo, Sharon, Khoo Teck Puat-National University Children’s Medical Institute, National University Health System, Singapore, Singapore
  • Lim, Yi Yang, Khoo Teck Puat-National University Children’s Medical Institute, National University Health System, Singapore, Singapore
  • Than, Mya, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
  • Ng, Kar Hui, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
  • Yap, Hui Kim, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
Background

15% of children with nephrotic syndrome (INS) have steroid-resistant disease, which portends a poor renal prognosis. Approximately half of these patients are able to achieve remission, but only with intensive immunosuppression including calcineurin inhibitors and/or Rituximab. Given the demonstrated role of Type 2 innate lymphoid cells (ILC2) in steroid-resistant allergic asthma, and the association between INS and atopic disease, this study aimed to examine ILC2 populations in steroid-resistant (SRNS) compared to steroid-dependent INS (SDNS).

Methods

We recruited 18 patients (age: 15.7±1.9 years) with SDNS or SRNS, 9 of whom were in partial/complete relapse (urine protein:creatinine ratio>0.1g/mmol). ILCs were identified as CD45+Lin-CD127+ cells. Of these, ILC2 were CRTH2+, and inflammatory ILC2 were CRTH2+ CD45RO+.

Results

Patients with SRNS had a higher proportion of ILC2 compared to SDNS patients (28.6±4.4% vs 11.7±2.4%, p=0.003), including inflammatory ILC2 (19.7±3.5% vs 7.9±2.1%, p=0.01). Similar findings were observed even if ILC2 was defined with greater stringency as CRTH2+CD127hi (p=0.02), while no concomitant changes were noted in ILC1 (p=0.61), ILC3 NCR+ (p=0.88) or ILC3 NCR- (p=0.45) populations. This elevation of ILC2 in SRNS compared to SDNS patients was more marked in relapse (35.4±2.4% vs 10.6±3.5%, p=0.002) compared to in remission (18.3±0.7% vs 12.7±3.6%, p=0.46). Correspondingly, ILC2 increased in relapse for SRNS patients (p=0.01) but not SDNS patients (p=0.99) (Figure).

Conclusion

ILC2s are activated in SRNS during relapse, but not in SDNS. If validated, ILC2s can be a potential target for therapy in SRNS.

Figure: ILC2 in patients with steroid-resistant (SR) and steroid-dependent (SD) nephrotic syndrome, in relapse and remission.

Funding

  • Government Support – Non-U.S.