Background/Aim: Although clinical and immunological findings in steroid-sensitive nephrotic syndrome (SSNS) favor an immunopathogenesis, many issues remain unsolved. Comprehensive studies analyzing cellular and humoral immunity in SSNS are scarce, and few studies addressed the effect of steroids on immunological factors. Methods: We therefore performed a cross-sectional study of T and B lymphocyte populations in 89 children during the different stages of the disease and related the findings to parameters of humoral immunity and treatment with steroids. Results: In untreated relapse, an increase in the proportion of activated CD3+ lymphocytes with a concomitant reduction of CD19+ B cells was noted compared to healthy controls. Conversely, patients with steroid dependency, relapsing on alternate-day steroids, showed a decline of the absolute numbers as well as proportion of CD4+ lymphocytes but a relative increase in CD19+ B cells, compared to healthy controls. Also untreated remission was characterized by an absolute and relative decrease in CD4+ lymphocytes compared to healthy controls which was accompanied by a significant increase in the proportion of CD8+ and also activated CD3+ lymphocytes. Steroid-induced remission resulted in suppression of absolute and relative CD4+, while absolute and relative B cells were upregulated in this group compared to untreated remission. Summary and Conclusion: Alterations of lymphocyte populations in SSNS are not limited to relapse but seem to be more pronounced in remission and show a different profile with steroid treatment. Changes of lymphocyte populations do not only affect T but also B lymphocytes, which may be of relevance in the pathogenesis of this disorder.

Keywords:
Steroid-sensitive nephrotic syndrome, Lymphocyte populations, T cells, B cells, Immunoglobulins
1.
Clark AG, Barratt TM: Steroid-responsive nephrotic syndrome; in Barratt TM, Avner ED, Harmon WE (eds): Pediatric Nephrology, ed 4. Baltimore, Lippincott Williams & Wilkins, 1999, pp 731–748.
2.
Shalhoub RJ: Pathogenesis of lipoid nephrosis: A disorder of T-cell function. Lancet 1974;ii: 556–560.
3.
Schnaper HW: The immune system in minimal change nephrotic syndrome. Pediatr Nephrol 1989;3:101–110.
4.
British Association for Paediatric Nephrology: Levamisole for corticosteroid-dependent nephrotic syndrome in childhood. Lancet 1991;337:1555–1557.
5.
Taube D, Brown Z, Williams DG: Impaired lymphocyte and suppressor cell function in minimal change nephropathy, membranous nephropathy and focal glomerulosclerosis. Clin Nephrol 1984;22:176–182.
6.
Matsumoto K, Kanmatsuse K: Interleukin-15 and interleukin-12 have an additive effect on the release of vascular permeability factor by peripheral blood mononuclear cells in normals and in patients with nephrotic syndrome. Clin Nephrol 1999;52:10–18.
7.
Giangiacomo J, Cleary TG, Cole BR, Hoffsten P, Robson AM: Serum immunoglobulins in the nephrotic syndrome: A possible cause of minimal-change nephrotic syndrome. N Engl J Med 1975;293:8–12.
8.
Fiser RT, Arnold WC, Charlton RK, Steele RW, Childress SH, Shirkey B: T-lymphocyte subsets in nephrotic syndrome. Kidney Int 1991;40:913–916.
9.
Kobayashi K, Yoshikawa N, Nakamura H: T-cell subpopulations in childhood nephrotic syndrome. Clin Nephrol 1994;41:253–258.
10.
Hulton SA, Shah V, Byrne MR, Morgan G, Barratt TM, Dillon MJ: Lymphocyte subpopulations, interleukin-2 and interleukin-2 receptor expression in childhood nephrotic syndrome. Pediatr Nephrol 1994;8:135–139.
11.
Neuhaus TJ, Shah V, Callard RE, Barratt TM: T-lymphocyte activation in steroid-sensitive nephrotic syndrome in childhood. Nephrol Dial Transplant 1995;10:1348–1352.
12.
Topaloglu R, Saatci U, Arikan M, Canpinar H, Bakkaloglu A, Kansu E: T-cell subsets, interleukin-2 receptor expression and production of interleukin-2 in minimal change nephrotic syndrome. Pediatr Nephrol 1994;8:649–652.
13.
Lama G, Luongo I, Tirino G, Borriello A, Carangio C, Salsano ME: T-lymphocyte populations and cytokines in childhood nephrotic syndrome. Am J Kidney Dis 2002;39:958–965.
14.
Grimbert P, Audard V, Remy P, Lang P, Sahali D: Recent approaches to the pathogenesis of minimal-change nephrotic syndrome. Nephrol Dial Transplant 2003;18:245–248.
15.
Kemper MJ, Meyer-Jark T, Lilova M, Muller-Wiefel DE: Combined T- and B-cell activation in childhood steroid-sensitive nephrotic syndrome. Clin Nephrol 2003;60:242–247.
16.
Kemper MJ, Altrogge H, Ganschow R, Muller-Wiefel DE: Serum levels of immunoglobulins and IgG subclasses in steroid sensitive nephrotic syndrome. Pediatr Nephrol 2002;17:413–417.
17.
Ehrich JH, Brodehl J: Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft für Pädiatrische Nephrologie. Eur J Pediatr 1993;152:357–361.
18.
Short versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children: Arbeitsgemeinschaft für Pädiatrische Nephrologie. Lancet 1988;i:380–383.
19.
Yan K, Nakahara K, Awa S, Nishibori Y, Nakajima N, Kataoka S, et al: The increase of memory T cell subsets in children with idiopathic nephrotic syndrome. Nephron 1998;79:274–278.
20.
Daniel V, Trautmann Y, Konrad M, Nayir A, Scharer K: T-lymphocyte populations, cytokines and other growth factors in serum and urine of children with idiopathic nephrotic syndrome. Clin Nephrol 1997;47:289–297.
21.
Frank C, Herrmann M, Fernandez S, Dirnecker D, Boswald M, Kolowos W, et al: Dominant T cells in idiopathic nephrotic syndrome of childhood. Kidney Int 2000;57:510–517.
22.
Zachwieja J, Bobkowski W, Dobrowolska-Zachwieja A, Lewandowska-Stachowiak M, Zaniew M, Maciejewski J: Intracellular cytokines of peripheral blood lymphocytes in nephrotic syndrome. Pediatr Nephrol 2002;17:733–740.
23.
Berg RE, Cordes CJ, Forman J: Contribution of CD8+ T cells to innate immunity: IFN-gamma secretion induced by IL-12 and IL-18. Eur J Immunol 2002;32:2807–2816.
24.
Remuzzi G, Chiurchiu C, Abbate M, Brusegan V, Bontempelli M, Ruggenenti P: Rituximab for idiopathic membranous nephropathy. Lancet 2002;360:923–924.
25.
Benz K, Dotsch J, Rascher W, Stachel D: Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy. Pediatr Nephrol 2004;19:794–797.
26.
Shi HZ, Sun JJ, Pan HL, Lu JQ, Zhang JL, Jiang JD: Alterations of T-lymphocyte subsets, soluble IL-2 receptor, and IgE in peripheral blood of children with acute asthma attacks. J Allergy Clin Immunol 1999;103:388–394.
27.
Verbruggen G, Herman L, Ackerman C, Mielants H, Veys EM: The effect of low doses of prednisolone on T-cell subsets in rheumatoid arthritis. Int J Immunopharmacol 1987;9:61–67.
28.
Zachwieja J, Dworacki G, Bobkowski W, Dobrowolska-Zachwieja A, Zaniew M, Maciejewski J: Increased apoptosis of peripheral blood lymphocytes in children with nephrotic syndrome. Pediatr Nephrol 2002;17:197–200.
29.
Yokoyama H, Shimizu M, Wada T, Yoshimoto K, Iwata Y, Shimizu K, et al: The beneficial effects of lymphocytapheresis for treatment of nephrotic syndrome. Ther Apher 2002;6:167–173.
30.
Birmele B, Thibault G, Nivet H, De Agostini A, Girardin EP: In vitro decrease of glomerular heparan sulfate by lymphocytes from idiopathic nephrotic syndrome patients. Kidney Int 2001;59:913–922.
31.
Sahali D, Pawlak A, Valanciute A, Grimbert P, Lang P, Remy P, et al: A novel approach to investigation of the pathogenesis of active minimal-change nephrotic syndrome using subtracted cDNA library screening. J Am Soc Nephrol 2002;13:1238–1247.
32.
Hulton SA, Neuhaus TJ, Callard RE, Dillon MJ, Barratt TM: Circulating interleukin 2 receptor (IL2R) in nephrotic syndrome. Kidney Int 1997;58(suppl):S83–S84.
33.
Mandreoli M, Beltrandi E, Casadei-Maldini M, Mancini R, Zucchelli A, Zucchelli P: Lymphocyte release of soluble IL-2 receptors in patients with minimal change nephropathy. Clin Nephrol 1992;37:177–182.
34.
Schnaper HW: The soluble immune response suppressor pathway in nephrotic syndrome. Semin Nephrol 1989;9:107–111.
35.
Warshaw BL, Check IJ, Hymes LC, DiRusso SC: Decreased serum transferrin concentration in children with the nephrotic syndrome: Effect on lymphocyte proliferation and correlation with serum immunoglobulin levels. Clin Immunol Immunopathol 1984;33:210–219.
© 2005 S. Karger AG, Basel
2005
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.