Pediatric Nephrology

, Volume 19, Issue 6, pp 627–632 | Cite as

Atopy, serum IgE, and interleukin-13 in steroid-responsive nephrotic syndrome

  • Wai Cheung
  • Chang-Li Wei
  • Ching-Ching Seah
  • Stanley C. Jordan
  • Hui-Kim Yap
Original Article


Earlier studies have demonstrated a strong association of steroid-responsive nephrotic syndrome (SRNS), atopy, and elevated serum IgE levels. Interleukin (IL-13) gene expression is significantly increased in children with SRNS in relapse. As interferon (IFN)-γ, IL-13, and IL-4 have regulatory effects on IgE synthesis, we examined the relationship between intracellular cytokine production and serum IgE levels in children with SRNS, in order to further define the reported association with atopy. The median serum IgE levels in nephrotic patients in relapse with (492 U/ml) or without atopy (561 U/ml) were significantly higher than those in remission (221 U/ml, P<0.002 or 90 U/ml, P<0.001, respectively) and non-atopic controls (177 U/ml) (P<0.001). The percentage of CD3+ IL-13-producing cells was significantly higher in nephrotic children in relapse, and correlated with the serum IgE levels during the active phase of the disease (r=0.90, P<0.001). These data suggest that the elevated serum IgE levels during relapses of SRNS were the result of upregulation of IL-13. This probably reflects some common immune activation following various stimuli, rather than a direct association with atopy.


Steroid-responsive nephrotic syndrome Immunoglobulins Atopy Th1/Th2 cytokine 



This work was supported by a grant (NMRC/0083/1995) from the National Medical Research Council, Singapore.


  1. 1.
    International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr 98:561–564PubMedGoogle Scholar
  2. 2.
    Hardwicke J, Soothill JF, Squire JR, Holti G (1959) Nephrotic syndrome and pollen hypersensitivity. Lancet I:499–502Google Scholar
  3. 3.
    Wittig HJ, Goldman AS (1970) Nephrotic syndrome associated with inhaled allergens. Lancet I:542–543Google Scholar
  4. 4.
    Reeves WG, Cameron JS, Johansson SG, Ogg CS, Peters DK, Weller RO (1975) Seasonal nephrotic syndrome. Description and immunological findings. Clin Allergy 5:121–137PubMedGoogle Scholar
  5. 5.
    Meadow SR, Sarsfield JK, Scott DG, Rajah SM (1981) Steroid-responsive nephrotic syndrome and allergy: immunological studies. Arch Dis Child 56:517–524PubMedGoogle Scholar
  6. 6.
    Rebien W, Müller-Wiefel DE, Wahn U, Schärer K (1981) IgE mediated hypersensitivity in children with idiopathic nephrotic syndrome. Int J Pediatr Nephrol 2:23–28PubMedGoogle Scholar
  7. 7.
    Lin CY, Lee BH, Lin CC, Chen WP (1990) A study of the relationship between childhood nephrotic syndrome and allergic diseases. Chest 47:1408–1411Google Scholar
  8. 8.
    Yap HK, Yip WCL, Lee BW, Ho TF, Teo J, Aw SE, Tay JSH (1983) The incidence of atopy in steroid-responsive nephrotic syndrome: clinical and immunological parameters. Ann Allergy 51:590–594PubMedGoogle Scholar
  9. 9.
    Florido JF, Diaz Pena JM, Belchi J, Estrada JL, Garcia Ara MC, Ojeda JA (1992) Nephrotic syndrome and respiratory allergy in childhood. J Invest Allergol Clin Immunol 2:136–140Google Scholar
  10. 10.
    Chan MK, Chan KW, Jones B (1987) Immunoglobulins (IgG, IgA, IgM, IgE) and complement components (C3, C4) in nephrotic syndrome due to minimal change and other forms of glomerulonephritis, a clue for steroid therapy? Nephron 47:125–130Google Scholar
  11. 11.
    Groshong T, Mendelson L, Mendoza S, Bazaral M, Hamburger R, Tune B (1973) Serum IgE in patients with minimal-change nephrotic syndrome. J Pediatr 83:767–771PubMedGoogle Scholar
  12. 12.
    Lagrue G, Laurent J, Hirbec G, Ansquer JC, Noirot C, Laurent G, Nebout T, Kestenbaum S (1984) Serum IgE in primary glomerular diseases. Nephron 984:5–9Google Scholar
  13. 13.
    Mansfield LE, Trygstad CW, Ajugwo RE, Heiner DC (1980) Serum concentrations of immunoglobins E and G and α2 macroglobulin in childhood renal disease. J Allergy Clin Immunol 66:227–232PubMedGoogle Scholar
  14. 14.
    Schulte-Wissermann H, Gortz W, Straub E (1979) IgE in patients with glomerulonephritis and minimal-change nephrotic syndrome. Eur J Pediatr 131:105–111PubMedGoogle Scholar
  15. 15.
    Shu KH, Lian JD, Yang YF, Lu YS, Wang JY (1988) Serum IgE in primary glomerular diseases and its clinical significance. Nephron 49:24–28PubMedGoogle Scholar
  16. 16.
    Yokoyama H, Kida H, Tani Y, Abe T, Tomosugi N, Koshino Y, Hattori N (1985) Immunodynamics of minimal change nephrotic syndrome in adults T and B lymphocyte subsets and serum immunoglobulin levels. Clin Exp Immunol 61:601–607PubMedGoogle Scholar
  17. 17.
    Warshaw BL, Check IJ (1989) IgG subclasses in children with nephrotic syndrome. Am J Clin Pathol 92:68–72PubMedGoogle Scholar
  18. 18.
    Mishra OP, Garg R, Usha, Ali Z, Das BK (1997) Immunoglobulins and circulating immune complexes in nephrotic syndrome. J Trop Pediatr 43:93–97PubMedGoogle Scholar
  19. 19.
    Shakib F, Hardwicke J, Stanworth DR, White RH (1977) Asymmetric depression in the serum level of IgG subclasses in patients with nephrotic syndrome. Clin Exp Immunol 28:506–511PubMedGoogle Scholar
  20. 20.
    Yap HK, Cheung W, Murugasu B, Sim SK, Seah CC, Jordan SC (1999) Th1 and Th2 cytokine mRNA profiles in childhood nephritic syndrome: evidence for increased IL-13 mRNA expression in relapse. J Am Soc Nephrol 10:529–537PubMedGoogle Scholar
  21. 21.
    Punnonen J, Aversa G, Cocks BG, McKenzie ANJ, Menon S, Zurawski G, De Waal Malefyt R, Vries JE de (1993) Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci U S A 90:3730–3734PubMedGoogle Scholar
  22. 22.
    Levy F, Kristofic C, Heusser C, Brinkmann V (1997) Role of IL-13 in CD4 T cell-dependent IgE production in atopy. Int Arch Allergy Immunol 112:49–58PubMedGoogle Scholar
  23. 23.
    Bacharier LB, Jabara H, Geha RS (1998) Molecular mechanisms of immunoglobulin E regulation. Int Arch Allergy Immunol 115:257–269CrossRefPubMedGoogle Scholar
  24. 24.
    Tenbrock K, Schubert A, Stapenhorst L, Kemper MJ, Gellermann J, Timmermann K, Müller-Wiefel DE, Querfeld U, Hoppe B, Michalk D (2002) Type I IgE receptor, interleukin 4 receptor and interleukin 13 polymorphisms in children with nephrotic syndrome. Clin Sci 102:507–512CrossRefPubMedGoogle Scholar
  25. 25.
    Picker LJ, Singh MK, Zdraveski Z, Treer JR, Waldrop SL, Bergstresser PR, Maino VC (1995) Direct demonstration of cytokine synthesis heterogeneity among human memory/effector T cells by flow cytometry. Blood 86:1408–1419PubMedGoogle Scholar
  26. 26.
    Schnaper HW (1989) The immune system in minimal change nephrotic syndrome. Pediatr Nephrol 3:101–110PubMedGoogle Scholar
  27. 27.
    Giangiacomo J, Cleary TG, Cole BR, Hoffsten P, Robson AM (1975) Serum immunoglobulins in nephrotic syndrome. A possible cause of minimal-change nephrotic syndrome. N Eng J Med 293:8–12Google Scholar
  28. 28.
    Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet II:556–560CrossRefGoogle Scholar
  29. 29.
    Kemper MJ, Altrogge H, Ganschow R, Müller-Wiefel DE (2002) Serum levels of immunoglobins and IgG subclasses in steroid sensitive nephrotic syndrome. Pediatr Nephrol 17:413–417CrossRefPubMedGoogle Scholar
  30. 30.
    Fuke Y, Endo M, Ohsawa I, Satomura A, Hidaka M, Fujita T, Ohi H (2002) Implication of elevated serum IgE levels in minimal change nephrotic syndrome. Nephron 91:769–770CrossRefPubMedGoogle Scholar
  31. 31.
    Capsoni F, Acerbi L, Bonora G, Perletti L, Ongari AM, Vanoli M, Zanussi C (1986) Phagocyte function and immunological findings in a Wiskott-Aldrich syndrome long-term survivor. J Clin Lab Immunol 19:91–97PubMedGoogle Scholar
  32. 32.
    Kikkawa Y, Kamikura K, Harajima T, Sekiguchi T, Kawai T (1973) Thymic alymphoplasia with hyper-IgE-globulinemia. Pediatrics 51:690–696PubMedGoogle Scholar
  33. 33.
    Bacharier LB, Geha RS (2000) Molecular mechanisms of IgE regulation. J Allergy Clin Immunol 105:S547–S558PubMedGoogle Scholar
  34. 34.
    Cho BS, Lee CE, Pyun KH (1992) Studies of the role of interleukin-4 and Fc∈RII in the pathogenesis of minimal change nephrotic syndrome. J Korean Med Sci 7:343–348PubMedGoogle Scholar
  35. 35.
    Cho BS, Yoon SR, Jang JY, Pyun KH, Lee CE (1999) Up-regulation of interleukin-4 and CD23/Fcepisilon in minimal change nephritic syndrome. Pediatr Nephrol 13:199–204CrossRefPubMedGoogle Scholar
  36. 36.
    Kimata H, Fujimoto M, Furusho K (1995) Involvement of interleukin (IL)-13, but not IL-4, in spontaneous IgE and IgG4 production in nephrotic syndrome. Eur J Immunol 25:1497–1501PubMedGoogle Scholar

Copyright information

© IPNA 2004

Authors and Affiliations

  • Wai Cheung
    • 1
  • Chang-Li Wei
    • 1
  • Ching-Ching Seah
    • 1
  • Stanley C. Jordan
    • 2
  • Hui-Kim Yap
    • 1
  1. 1.Department of PediatricsNational University of SingaporeSingapore
  2. 2.Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical CenterUCLA School of MedicineLos AngelesUSA

Personalised recommendations