title: The effect of systemic corticosteroids on the innate and adaptive immune system in children with steroid responsive nephrotic syndrome.
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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  • 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.
authors.affiliation: Research and Training Hospital, Division of Pediatric Allergy and Immunology, Marmara University, Mimar Sinan Cad. No: 41, 34890, Istanbul, Turkiye.
authors.forename: Hatice Ezgi
authors.initials: HE
authors.lastname: Baris
authors.affiliation: Research and Training Hospital, Division of Pediatric Allergy and Immunology, Marmara University, Mimar Sinan Cad. No: 41, 34890, Istanbul, Turkiye. safabaris@hotmail.com.
authors.forename: Safa
authors.initials: S
authors.lastname: Baris
authors.affiliation: Research and Training Hospital, Division of Pediatric Allergy and Immunology, Marmara University, Mimar Sinan Cad. No: 41, 34890, Istanbul, Turkiye.
authors.forename: Elif
authors.initials: E
authors.lastname: Karakoc-Aydiner
authors.affiliation: Research and Training Hospital, Division of Pediatric Nephrology, Marmara University, Istanbul, Turkiye.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Gokce
authors.affiliation: Research and Training Hospital, Division of Pediatric Nephrology, Marmara University, Istanbul, Turkiye.
authors.forename: Nurdan
authors.initials: N
authors.lastname: Yildiz
authors.affiliation: Research and Training Hospital, Division of Pediatric Allergy and Immunology, Marmara University, Mimar Sinan Cad. No: 41, 34890, Istanbul, Turkiye.
authors.forename: Dilek
authors.initials: D
authors.lastname: Cicekkoku
authors.affiliation: Research and Training Hospital, Division of Pediatric Allergy and Immunology, Marmara University, Mimar Sinan Cad. No: 41, 34890, Istanbul, Turkiye.
authors.forename: Ismail
authors.initials: I
authors.lastname: Ogulur
authors.affiliation: Research and Training Hospital, Division of Pediatric Allergy and Immunology, Marmara University, Mimar Sinan Cad. No: 41, 34890, Istanbul, Turkiye.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ozen
authors.affiliation: Research and Training Hospital, Division of Pediatric Nephrology, Marmara University, Istanbul, Turkiye.
authors.forename: Harika
authors.initials: H
authors.lastname: Alpay
authors.affiliation: Research and Training Hospital, Division of Pediatric Allergy and Immunology, Marmara University, Mimar Sinan Cad. No: 41, 34890, Istanbul, Turkiye.
authors.forename: Isil
authors.initials: I
authors.lastname: Barlan
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007165:Immunosuppression Therapy / Q000379:methods*; D007223:Infant; D008297:Male; D009404:Nephrotic Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D011239:Prednisolone / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D011239:Prednisolone
keywords: Children; Corticosteroids; Immunosuppression; Lymphocytes; Nephrotic syndrome; Neutrophils
references.citation: Immunology. 2012 Jun;136(2):198-207
references.pmid: 22321054
references.citation: Pediatr Nephrol. 1994 Apr;8(2):135-9
references.pmid: 8018488
references.citation: J Immunol. 1996 Jun 1;156(11):4422-8
references.pmid: 8666816
references.citation: Lancet. 1974 Sep 7;2(7880):556-60
references.pmid: 4140273
references.citation: Pediatr Nephrol. 2013 Mar;28(3):415-26
references.pmid: 23052651
references.citation: Pediatrics. 2009 Aug;124(2):747-57
references.pmid: 19651590
references.citation: Ann Allergy Asthma Immunol. 2006 Jul;97(1):113-6
references.pmid: 16892792
references.citation: Inflamm Res. 2014 Jan;63(1):1-12
references.pmid: 24121975
references.citation: Annu Rev Immunol. 2000;18:309-45
references.pmid: 10837061
references.citation: Mol Endocrinol. 2011 Jul;25(7):1075-86
references.pmid: 21511881
references.citation: Clin Nephrol. 1995 Nov;44(5):290-8
references.pmid: 8605708
references.citation: Asian Pac J Allergy Immunol. 1988 Jun;6(1):23-8
references.pmid: 2901842
references.citation: Pediatrics. 1987 Aug;80(2):225-30
references.pmid: 3302924
references.citation: Ital J Pediatr. 2013 Jul 06;39:42
references.pmid: 23830064
references.citation: World J Pediatr. 2015 Feb;11(1):21-8
references.pmid: 25822700
references.citation: Pediatr Nephrol. 2008 Aug;23(8):1269-79
references.pmid: 18465150
references.citation: MMWR Recomm Rep. 2011 Jan 28;60(2):1-64
references.pmid: 21293327
references.citation: Pediatr Nephrol. 2009 May;24(5):1033-8
references.pmid: 19153775
references.citation: N Engl J Med. 1975 Jul 3;293(1):8-12
references.pmid: 1079322
references.citation: J Lab Clin Med. 1978 Apr;91(4):625-34
references.pmid: 76667
references.citation: Kidney Int. 1991 Nov;40(5):913-6
references.pmid: 1762295
references.citation: Ann Intern Med. 1976 Mar;84(3):304-15
references.pmid: 769625
references.citation: Am J Nephrol. 2005 Mar-Apr;25(2):132-7
references.pmid: 15855740
references.citation: Clin Exp Immunol. 1996 Mar;103(3):482-90
references.pmid: 8608650
references.citation: J Clin Invest. 1985 Feb;75(2):754-61
references.pmid: 3871795
references.citation: Int Immunol. 1995 Apr;7(4):591-5
references.pmid: 7547686
references.citation: Arch Dermatol. 2010 Jul;146(7):767-74
references.pmid: 20479291
references.citation: Mol Cell Endocrinol. 2011 Mar 15;335(1):2-13
references.pmid: 20398732
references.citation: Clin Exp Nephrol. 2010 Dec;14(6):578-83
references.pmid: 20686809
references.citation: Arch Neurol. 2001 Jan;58(1):91-7
references.pmid: 11176941
references.citation: Lupus. 2001;10(3):140-7
references.pmid: 11315342