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The effect of systemic corticosteroids on the innate and adaptive immune system in children with steroid responsive nephrotic syndrome

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Abstract

The severity and duration of immunosuppression caused by corticosteroids (CSs) usage have not been extensively studied. We aimed to investigate the effects of CSs on the various compartments of immune system in relation to timing of initiation and persistence of therapy. Pediatric patients with idiopathic nephrotic syndrome (NS) treated with 2 mg/kg/day prednisolone and healthy control (HC) were enrolled. Blood samples were drawn for immunologic analyses at baseline and at the first and second weeks and first, second, and third months of CS therapy in addition to first and second weeks and first, second, and third months of discontinuation. Fourteen patients (M/F, 7/7) between 1 and 8 years old were evaluated. Untreated NS exhibited high absolute lymphocyte count (ALC)(p = 0.010), absolute CD3+ T cells (p = 0.020) and absolute CD8+ T cells (p = 0.006) compared to HC. Suppression in ALC was observed and nadir value was noted at first month of therapy compared to baseline (p = 0.002). The CD4+ (p = 0.036) and CD8+ T cell (p = 0.013) counts decreased significantly at the first week of treatment compared to baseline. While baseline B cell counts was indifferent from HC, gradually increased in 2 weeks of CS initiation and decreased during the treatment with a statistical significance compared to HC (p = 0.010). However, after cessation of CS, B cell counts continued to decline and found to be significantly different than baseline at first week (p = 0.008) and at third month (p = 0.040).

Conclusion: Apart from baseline lymphocyte subset changing observed in untreated NS patients, our data implies that T cells were suppressed very early in the CS treatment. Interestingly, depressed B cell counts were detected later but persisted even after CS cessation. Due to early decrease in T cells, it would be beneficial to assume the patients as immunosuppressed at the very beginning of CS treatment to avoid infections.

What is Known:

• Corticosteroids (CSs) are widely used for a variety of diseases including nephrotic syndrome, which is related with complex immune disturbance including T and B cells dysfunctions.

• CSs induce neutrophilic leukocytosis concomitant with lymphopenia and eosinopenia leading to immunosupression.

What is New:

• T cell subsets and proliferation are susceptible to CSs more than B cells; however, the reversibility is faster with dose reduction in CS.

• The change of B cells and B cell subtypes (CD27 + memory) shows prolonged effect of CSs on B cells which may alter antibody production even after 3 months of CSs cessation.

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Abbreviations

CS:

Corticosteroid

GR:

Glucocorticoid receptor

NS:

Nephrotic syndrome

HC:

Healthy control

CFSE:

Carboxyfluorescein diacetate, succinimidyl ester

PBMC:

Peripheral Blood Mononuclear Cells

WBC:

White blood cell

ALC:

Absolute lymphocyte count

ANC:

Absolute neutrophil count

CD4+ :

Helper T cells

CD8+ :

Cytotoxic T cells

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Authors’ contributions

HEB followed up patients, data collection and analysis, and drafting of the manuscript.

SB had substantial contributions to the data analysis and drafting of the manuscript.

EKA had participated in writing of the manuscript.

IG followed up patients, data collection, and commented on the manuscript draft.

NY followed up patients and commented on the manuscript draft.

DC performed flow cytometer analysis.

IO performed the lymphocyte proliferation studies and participated in writing of the manuscript.

AO had substantial contribution to the conception and commented on the manuscript draft.

HA had substantial contribution to the conception and commented on the manuscript draft.

IB supervised the study, had substantial contribution to the conception, and commented on the manuscript draft.

Author information

Authors and Affiliations

  1. Research and Training Hospital, Division of Pediatric Allergy and Immunology, Marmara University, Mimar Sinan Cad. No: 41, 34890, Istanbul, Turkiye

    Hatice Ezgi Baris, Safa Baris, Elif Karakoc-Aydiner, Dilek Cicekkoku, Ismail Ogulur, Ahmet Ozen & Isil Barlan

  2. Research and Training Hospital, Division of Pediatric Nephrology, Marmara University, Istanbul, Turkiye

    Ibrahim Gokce, Nurdan Yildiz & Harika Alpay

Authors
  1. Hatice Ezgi Baris
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  2. Safa Baris
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  3. Elif Karakoc-Aydiner
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  6. Dilek Cicekkoku
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  7. Ismail Ogulur
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  8. Ahmet Ozen
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  10. Isil Barlan
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Corresponding author

Correspondence to Safa Baris.

Ethics declarations

The study protocol was approved by the local ethics committee of Marmara University (IRB number: 00009067); all procedures were in accordance with the 1964 Helsinki declaration, and a written informed consent was obtained from all parents. Due to the young age of our patients, a simple oral description of the study was given to participating child in the presence of their parent(s) and a verbal assent was requested.

Funding

No sources of financial and material support to be declared.

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Marmara University and with the 1964 Helsinki declaration.

Informed consent

Informed consent was obtained for the parents of infants included in the study.

Additional information

Communicated by David Nadal

Revisions received: 18 November 2015; 9 January 2016

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Baris, H.E., Baris, S., Karakoc-Aydiner, E. et al. The effect of systemic corticosteroids on the innate and adaptive immune system in children with steroid responsive nephrotic syndrome. Eur J Pediatr 175, 685–693 (2016). https://doi.org/10.1007/s00431-016-2694-x

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  • DOI: https://doi.org/10.1007/s00431-016-2694-x

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