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Erschienen in: European Journal of Pediatrics 5/2016

30.01.2016 | Original Article

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

verfasst von: Hatice Ezgi Baris, Safa Baris, Elif Karakoc-Aydiner, Ibrahim Gokce, Nurdan Yildiz, Dilek Cicekkoku, Ismail Ogulur, Ahmet Ozen, Harika Alpay, Isil Barlan

Erschienen in: European Journal of Pediatrics | Ausgabe 5/2016

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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.
Literatur
1.
Zurück zum Zitat Ashwell JD, Lu FW, Vacchio MS (2000) Glucocorticoids in T cell development and function. Ann Rev Immunol 18:309–345CrossRef Ashwell JD, Lu FW, Vacchio MS (2000) Glucocorticoids in T cell development and function. Ann Rev Immunol 18:309–345CrossRef
2.
Zurück zum Zitat Baker C, Pickering L, Chilton L et al (2011) General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 60:1–64 Baker C, Pickering L, Chilton L et al (2011) General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 60:1–64
3.
5.
Zurück zum Zitat Cupps TR, Gerrard TL, Falkoff RJ, Whalen G, Fauci AS (1985) Effects of in vitro corticosteroids on B cell activation, proliferation, and differentiation. J Clin Invest 75:754–761CrossRefPubMedPubMedCentral Cupps TR, Gerrard TL, Falkoff RJ, Whalen G, Fauci AS (1985) Effects of in vitro corticosteroids on B cell activation, proliferation, and differentiation. J Clin Invest 75:754–761CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Fan PT, Yu DT, Clements PJ, Fowlston S, Eisman J, Bluestone R (1978) Effect of corticosteroids on the human immune response: comparison of one and three daily 1 gm intravenous pulses of methylprednisolone. J Lab Clin Med 91:625–634PubMed Fan PT, Yu DT, Clements PJ, Fowlston S, Eisman J, Bluestone R (1978) Effect of corticosteroids on the human immune response: comparison of one and three daily 1 gm intravenous pulses of methylprednisolone. J Lab Clin Med 91:625–634PubMed
7.
Zurück zum Zitat Fauci AS, Dale DC, Balow JE (1976) Glucocorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med 84:304–315CrossRefPubMed Fauci AS, Dale DC, Balow JE (1976) Glucocorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med 84:304–315CrossRefPubMed
8.
Zurück zum Zitat Fedor ME, Rubinstein A (2006) Effects of long-term low-dose corticosteroid therapy on humoral immunity. Ann Allergy Asthma Immunol 97:113–116CrossRefPubMed Fedor ME, Rubinstein A (2006) Effects of long-term low-dose corticosteroid therapy on humoral immunity. Ann Allergy Asthma Immunol 97:113–116CrossRefPubMed
9.
Zurück zum Zitat Fiser RT, Arnold WC, Charlton RK, Steele RW, Childress SH, Shirkey B (1991) T-lymphocyte subsets in nephrotic syndrome. Kidney Int 40:913–916CrossRefPubMed Fiser RT, Arnold WC, Charlton RK, Steele RW, Childress SH, Shirkey B (1991) T-lymphocyte subsets in nephrotic syndrome. Kidney Int 40:913–916CrossRefPubMed
11.
Zurück zum Zitat Giangiacomo J, Cleary TG, Cole BR, Hoffstein P, Robson AM (1975) Serum immunoglobulins in the nephrotic syndrome. A possible cause of minimal change nephrotic syndrome. N Engl J Med 293:08–12CrossRef Giangiacomo J, Cleary TG, Cole BR, Hoffstein P, Robson AM (1975) Serum immunoglobulins in the nephrotic syndrome. A possible cause of minimal change nephrotic syndrome. N Engl J Med 293:08–12CrossRef
13.
Zurück zum Zitat Guigonis V, Dallocchio A, Baudouin V et al (2008) Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol 23:1269–1279CrossRefPubMed Guigonis V, Dallocchio A, Baudouin V et al (2008) Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol 23:1269–1279CrossRefPubMed
14.
Zurück zum Zitat Hulton SA, Shah V, Byrne MR, Morgan G, Barratt TM, Dillon MJ (1994) Lymphocyte subpopulations, interleukin-2 and interleukin-2 receptor expression in childhood nephrotic syndrome. Pediatr Nephrol 8:135–139CrossRefPubMed Hulton SA, Shah V, Byrne MR, Morgan G, Barratt TM, Dillon MJ (1994) Lymphocyte subpopulations, interleukin-2 and interleukin-2 receptor expression in childhood nephrotic syndrome. Pediatr Nephrol 8:135–139CrossRefPubMed
16.
Zurück zum Zitat Kanai T, Shiraishi H, Yamagata T et al (2010) Th2 cells predominate in idiopathic steroid-sensitive nephrotic syndrome. Clin Exp Nephrol 14:578–583CrossRefPubMed Kanai T, Shiraishi H, Yamagata T et al (2010) Th2 cells predominate in idiopathic steroid-sensitive nephrotic syndrome. Clin Exp Nephrol 14:578–583CrossRefPubMed
17.
18.
19.
Zurück zum Zitat Kemper MJ, Zepf K, Klaassen I, Link A, Muller-Wiefel DE (2005) Changes of lymphocyte populations in pediatric steroid-sensitive nephrotic syndrome are more pronounced in remission than in relapse. Am J Nephrol 25:132–137CrossRefPubMed Kemper MJ, Zepf K, Klaassen I, Link A, Muller-Wiefel DE (2005) Changes of lymphocyte populations in pediatric steroid-sensitive nephrotic syndrome are more pronounced in remission than in relapse. Am J Nephrol 25:132–137CrossRefPubMed
20.
Zurück zum Zitat Lanza L, Scudeletti M, Puppo F et al (1996) Prednisone increases apoptosis in in vitro activated human peripheral blood T lymphocytes. Clin Exp Immunol 103:482–490CrossRefPubMedPubMedCentral Lanza L, Scudeletti M, Puppo F et al (1996) Prednisone increases apoptosis in in vitro activated human peripheral blood T lymphocytes. Clin Exp Immunol 103:482–490CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Leussink VI, Jung S, Merschdorf U, Toyka KV, Gold R (2001) High-dose methylprednisolone therapy in multiple sclerosis induces apoptosis in peripheral blood leukocytes. Arch Neurol 58:91–97CrossRefPubMed Leussink VI, Jung S, Merschdorf U, Toyka KV, Gold R (2001) High-dose methylprednisolone therapy in multiple sclerosis induces apoptosis in peripheral blood leukocytes. Arch Neurol 58:91–97CrossRefPubMed
23.
Zurück zum Zitat Meagher LC, Cousin JM, Seckl JR, Haslett C (1966) Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. J Immunol 156:4422–4428 Meagher LC, Cousin JM, Seckl JR, Haslett C (1966) Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. J Immunol 156:4422–4428
24.
Zurück zum Zitat Nijhuis EW, Hinloopen B, van Lier RA, Nagelkerken L (1995) Differential sensitivity of human naive and memory CD4+ T cells for dexamethasone. Int Immunol 7:591–595CrossRefPubMed Nijhuis EW, Hinloopen B, van Lier RA, Nagelkerken L (1995) Differential sensitivity of human naive and memory CD4+ T cells for dexamethasone. Int Immunol 7:591–595CrossRefPubMed
25.
Zurück zum Zitat Nilganuwonge S, Harisdangkul V, Rockhold L, Lewis RE, Cruse JM (1988) Lymphocyte subset T4/T8 ratio in systemic lupus erythematosus: correlation with disease activity, laboratory abnormalities and treatment. Asian Pac J Allergy Immunol 6:23–28PubMed Nilganuwonge S, Harisdangkul V, Rockhold L, Lewis RE, Cruse JM (1988) Lymphocyte subset T4/T8 ratio in systemic lupus erythematosus: correlation with disease activity, laboratory abnormalities and treatment. Asian Pac J Allergy Immunol 6:23–28PubMed
26.
Zurück zum Zitat Pereira Wde F, Brito Melo GE, Guimarães FT, Carvalho TG, Mateo EC, Simões E, Silva AC (2014) The role of the immune system in idiopathic nephrotic syndrome: a review of clinical and experimental studies. Inflamm Res 63:1–12CrossRefPubMed Pereira Wde F, Brito Melo GE, Guimarães FT, Carvalho TG, Mateo EC, Simões E, Silva AC (2014) The role of the immune system in idiopathic nephrotic syndrome: a review of clinical and experimental studies. Inflamm Res 63:1–12CrossRefPubMed
27.
Zurück zum Zitat Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 2:556–560.22CrossRefPubMed Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 2:556–560.22CrossRefPubMed
28.
Zurück zum Zitat Tornatore KM, Reed K, Venuto R (1995) 24-hour immunologic assessment of CD4+ and CD8+ lymphocytes in renal transplant recipients receiving chronic methylprednisolone. Clin Nephrol 44:290–298PubMed Tornatore KM, Reed K, Venuto R (1995) 24-hour immunologic assessment of CD4+ and CD8+ lymphocytes in renal transplant recipients receiving chronic methylprednisolone. Clin Nephrol 44:290–298PubMed
31.
Zurück zum Zitat Younger RE, Gerber PS, Herrod HG, Cohen RM, Crawford LV (1987) Intravenous methylprednisolone efficacy in status asthmaticus of childhood. Pediatrics 80:225–230PubMed Younger RE, Gerber PS, Herrod HG, Cohen RM, Crawford LV (1987) Intravenous methylprednisolone efficacy in status asthmaticus of childhood. Pediatrics 80:225–230PubMed
Metadaten
Titel
The effect of systemic corticosteroids on the innate and adaptive immune system in children with steroid responsive nephrotic syndrome
verfasst von
Hatice Ezgi Baris
Safa Baris
Elif Karakoc-Aydiner
Ibrahim Gokce
Nurdan Yildiz
Dilek Cicekkoku
Ismail Ogulur
Ahmet Ozen
Harika Alpay
Isil Barlan
Publikationsdatum
30.01.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Pediatrics / Ausgabe 5/2016
Print ISSN: 0340-6199
Elektronische ISSN: 1432-1076
DOI
https://doi.org/10.1007/s00431-016-2694-x

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