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European Journal of Pediatrics

, Volume 175, Issue 5, pp 685–693 | Cite as

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

  • Hatice Ezgi Baris
  • Safa BarisEmail author
  • Elif Karakoc-Aydiner
  • Ibrahim Gokce
  • Nurdan Yildiz
  • Dilek Cicekkoku
  • Ismail Ogulur
  • Ahmet Ozen
  • Harika Alpay
  • Isil Barlan
Original Article

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.

Keywords

Corticosteroids Nephrotic syndrome Children Lymphocytes Neutrophils Immunosuppression 

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

Notes

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.

Compliance with ethical standards

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.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Hatice Ezgi Baris
    • 1
  • Safa Baris
    • 1
    Email author
  • Elif Karakoc-Aydiner
    • 1
  • Ibrahim Gokce
    • 2
  • Nurdan Yildiz
    • 2
  • Dilek Cicekkoku
    • 1
  • Ismail Ogulur
    • 1
  • Ahmet Ozen
    • 1
  • Harika Alpay
    • 2
  • Isil Barlan
    • 1
  1. 1.Research and Training Hospital, Division of Pediatric Allergy and ImmunologyMarmara UniversityIstanbulTurkiye
  2. 2.Research and Training Hospital, Division of Pediatric NephrologyMarmara UniversityIstanbulTurkiye

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