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The immunopathogenesis of idiopathic nephrotic syndrome: a narrative review of the literature

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Abstract

Idiopathic nephrotic syndrome (INS) is a common glomerular disease in childhood, and the immunological involvement in the pathogenesis of non-genetic INS, although not fully elucidated, is evident. This narrative review aims to offer a concise and in-depth view of the current knowledge on the immunological mechanisms of the development of INS as well as the role of the immunological components of the disease in the responsiveness to treatment. T cell immunity appears to play a major role in the INS immunopathogenesis and has been the first to be linked to the disease. Various T cell immunophenotypes are implicated in INS, including T-helper-1, T-helper-2, T-helper-17, and T regulatory cells, and various cytokines have been proposed as surrogate biomarkers of the disease; however, no distinct T helper or cytokine profile has been conclusively linked to the disease. More recently, the recognition of the role of B cell mediated immunity and the various B cell subsets that are dysregulated in patients with INS have led to new hypotheses on the underlying immunological causes of INS. Finally, the disambiguation of the exact mechanisms of the INS development in the future may be the key to the development of more targeted personalized approaches in managing INS.

Conclusions: INS demonstrates particularly interesting immunopathogenetic pathways, in which multiple interactions between T cell and B cell immunity and the podocyte are involved. The disambiguation of these pathways will provide promising novel therapeutic targets in INS.

What is Known:

• INS is the most common glomerular disease in the paediatric population, and its onset and relapses have been linked to various immunological triggers.

• Multiple immunological mechanisms have been implicated in the pathogenesis of INS; however, no single distinct immunological profile has been recognized.

What is New:

• Th17 cells and Treg cells play an important role in the immune dysregulation in INS.

• Transitional B cell levels as well as the transitional/memory B cell ratio have been correlated to nephrotic relapses and have been proposed as biomarkers of INS relapses in SSNS patients.

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Abbreviations

CNIs:

Calcineurin inhibitors

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

EBNA1:

Epstein-Barr nuclear antigen 1

FSGS:

Focal segmental glomerulosclerosis

HLA:

Human leukocyte antigen

INS:

Idiopathic nephrotic syndrome

IL:

Interleukin

IL-2R:

IL-2 receptor

IL-4Rα:

IL-4 receptor alpha chain

MHC:

Major histocompatibility complex

MCD:

Minimal change disease

SRNS:

Steroid-resistant nephrotic syndrome

SSNS:

Steroid-sensitive nephrotic syndrome

STAT6:

Signal transducer and activator of transcription 6

Th1:

T-helper 1

Th17:

T-helper 17

Th2:

T-helper 2

Treg:

T-regulatory

TLR:

Toll-like receptor

TNF-α:

Tumour necrosis factor-alpha

UCHL1:

Ubiquitin carboxyl-terminal hydrolase L1

ZO-1:

Zonula occludens-1

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Authors and Affiliations

  1. Immunobiology and Vaccinology Research Laboratory, First Department of Paediatrics, School of Medicine, “Aghia Sophia” Children’s Hospital, National and Kapodistrian University of Athens, Athens, Greece

    Konstantina Kitsou & Vana Spoulou

  2. Department of Nephrology, “P. and A. Kyriakou” Children’s Hospital, Athens, Greece

    Varvara Askiti & Andromachi Mitsioni

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  1. Konstantina Kitsou
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  2. Varvara Askiti
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Conceptualization: Konstantina Kitsou, Vana Spoulou; Writing — original draft preparation: Konstantina Kitsou, Vana Spoulou; Writing — review and editing: Konstantina Kitsou, Varvara Askiti, Andromachi Mitsioni, Vana Spoulou; Supervision: Vana Spoulou.

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Kitsou, K., Askiti, V., Mitsioni, A. et al. The immunopathogenesis of idiopathic nephrotic syndrome: a narrative review of the literature. Eur J Pediatr 181, 1395–1404 (2022). https://doi.org/10.1007/s00431-021-04357-9

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  • DOI: https://doi.org/10.1007/s00431-021-04357-9

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