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Serum levels of galactose-deficient IgA in children with IgA nephropathy and Henoch-Schönlein purpura

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Abstract

IgA nephropathy and Henoch-Schönlein purpura nephritis (HSPN) are related diseases characterized by deposits of IgA1-containing immune complexes in the renal mesangium. Adult patients with IgA nephropathy have aberrantly glycosylated IgA1 (galactose-deficient O-linked glycans) in the circulation and renal deposits. However, IgA1 glycosylation has not been studied in pediatric patients with IgA nephropathy. Using our quantitative lectin enzyme-linked immunosorbent assay (ELISA) test, we measured serum levels of galactose-deficient IgA1 of children with IgA nephropathy and HSPN and controls. Children with IgA nephropathy and HSPN had serum levels higher than those of healthy children or renal-disease controls with C1q nephropathy. Furthermore, lectin ELISA identified patients with HSPN whose clinical course mimicked that of IgA nephropathy. In summary, pediatric patients with IgA nephropathy and HSPN have an aberrancy in the glycosylation in IgA1 O-linked glycans that is similar to that in adults with IgA nephropathy.

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References

  1. D’Amico G (1987) The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med 64:709–727

    PubMed  Google Scholar 

  2. Delos Santos NM, Wyatt RJ (2004) Pediatric IgA nephropathies: Clinical aspects and therapeutic approaches. Semin Nephrol 24:269–286

    Article  Google Scholar 

  3. Saulsbury FT (2001) Henoch-Schönlein purpura. Curr Opin Rheumatol 13:35–40

    Article  CAS  Google Scholar 

  4. Levy M, Broyer M, Arsan A, Levy-Bentolila D, Habib R (1976) Anaphylactoid purpura nephritis in childhood: Natural history and immunopathology. Adv Nephrol 6:183–228

    CAS  Google Scholar 

  5. Evans DJ, Gwynn-Williams D, Peters DK, Sissons JG, Boulton-Jones JM, Ogg CS, Cameron JS, Hoffbrand BI (1973) Glomerular deposition of properdin in Henoch-Schönlein purpura syndrome and idiopathic focal glomerulonephritis. Br Med J 11:326–328

    Article  Google Scholar 

  6. Meadow SR, Scott DG (1985) Berger disease: Henoch-Schönlein syndrome without the rash. J Pediatr 106:27–32

    Article  CAS  Google Scholar 

  7. Levy M (1989) Familial cases of Berger’s disease and anaphylactoid purpura: more frequent than previously thought. Am J Med 87:246–248

    Article  CAS  Google Scholar 

  8. Nakamoto Y, Asano Y, Dohi K, Fujioka M, Iida H, Kida H, Kibe Y, Hattori N, Takeuchi J (1978) Primary IgA glomerulonephritis and Schonlein-Henoch purpura nephritis: clinicopathological and immunohistological characteristics. Q J Med 47:495–516

    CAS  PubMed  Google Scholar 

  9. Waldo FB (1988) Is Henoch-Schönlein purpura the systemic form of IgA nephropathy? Am J Kidney Dis 12:373–377

    Article  CAS  Google Scholar 

  10. Andre PM, Le Pogamp P, Chevet D (1990) Impairment of jacalin binding to serum IgA in IgA nephropathy. J Clin Lab Anal 4:115–119

    Article  CAS  Google Scholar 

  11. Mestecky J, Tomana M, Crowley-Nowick PA, Moldoveanu Z, Julian BA, Jackson S (1993) Defective galactosylation and clearance of IgA1 molecules as a possible etiopathogenic factor in IgA nephropathy. Contrib Nephrol 104:172–182

    Article  CAS  Google Scholar 

  12. Allen AC, Harper SJ, Feehally J (1995) Galactosylation of N- and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy. Clin Exp Immunol 100:470–474

    Article  CAS  Google Scholar 

  13. Tomana M, Matousovic K, Julian BA, Radl J, Konecny K, Mestecky J (1997) Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in complexes with IgG. Kidney Int 52:509–516

    Article  CAS  Google Scholar 

  14. Allen AC, Willis FR, Beattie TJ, Feehally J (1998) Abnormal IgA glycosylation in Henoch-Schönlein purpura restricted to patients with clinical nephritis. Nephrol Dial Transplant 13:930–934

    Article  CAS  Google Scholar 

  15. Coppo R, Basolo B, Martina G, Rollino C, De Marchi M, Giacchino F, Mazzucco G, Messina M, Piccoli G (1982) Circulating immune complexes containing IgA, IgG and IgM in patients with primary IgA nephropathy and with Henoch-Schönlein nephritis. Correlation with clinical and histologic signs of activity. Clin Nephrol 18:230–239

    CAS  PubMed  Google Scholar 

  16. Amore A, Cirina P, Conti G, Brusa P, Peruzzi L, Coppo R (2001) Glycosylation of circulating IgA in patients with IgA nephropathy modulates proliferation and apoptosis of mesangial cells. J Am Soc Nephrol 12:1862–1871

    CAS  PubMed  Google Scholar 

  17. Coppo R, Amore A (2004) Aberrant glycosylation in IgA nephropathy (IgAN). Kidney Int 65:1544–1547

    Article  CAS  Google Scholar 

  18. Novak J, Tomana M, Matousovic K, Brown R, Hall S, Novak L, Julian BA, Wyatt RJ, Mestecky J (2005) IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells. Kidney Int 67:504–513

    Article  CAS  Google Scholar 

  19. Hogg R, Tomana M, Gray J, Mestecky J (1997) Deficient IgA1 galactosylation in children with idiopatic IgA nephropathy (IgAN) and Henoch-Schönlein nephritis (HSPN). J Am Soc Nephrol 8:88A

    Google Scholar 

  20. Moore JS, Kulhavy R, Tomana M, Moldoveanu Z, Suzuki H, Brown R, Hall S, Kilian M, Poulsen K, Mestecky J, Julian BA, Novak J (2007) Reactivities of N-acetylgalactosamine-specific lectins with human IgA1 proteins. Mol Immunol 44:2598–2604

    Article  CAS  Google Scholar 

  21. Moldoveanu Z, Wyatt RJ, Lee J, Tomana M, Julian BA, Mestecky J, Huang W-Q, Anreddy SR, Hastings MC, Lau KK, Cook WJ, Novak J (2007) Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels. Kidney Int 71:134–138

    Article  Google Scholar 

  22. Schwartz GJ, Haycock GB, Edelman CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and serum creatinine. Pediatrics 58:522–526

    Google Scholar 

  23. Tomana M, Novak J, Julian BA, Matousovic K, Konecny K, Mestecky J (1999) Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies. J Clin Invest 104:73–81

    Article  CAS  Google Scholar 

  24. Yoshikawa N, Ito H, Nakamura H (1992) Prognostic indicators in childhood IgA nephropathy. Nephron 60:60–67

    Article  CAS  Google Scholar 

  25. Ariceta G, Gallego N, Lopez-Fernandez Y, Vallo A, Quintella MJ, Rodriquez Soriano J (2001) Long-term prognosis of childhood IgA nephropathy in adult life. Med Clin 116:361–364

    Article  CAS  Google Scholar 

  26. Delos Santos NM, Ault BH, Gharavi AG, Kritchevsky SB, Quasney MW, Jackson EC, Fisher KA, Woodford SY, Mitchell BL, Gaber LW, Arheart KL, Wyatt RJ (2002) Angiotensin-converting enzyme genotype and outcome in pediatric IgA nephropathy. Pediatr Nephrol 17:496–502

    Article  Google Scholar 

  27. Yoshikawa N, Iijima K, Matsuyama S, Suzuki J, Kameda A, Okada S, Nakamura H (1990) Repeat renal biopsy in children with IgA nephropathy. Clin Nephrol 33:160–167

    CAS  PubMed  Google Scholar 

  28. Xu LX, Zhao MH (2005) Aberrantly glycosylated serum IgA1 are closely associated with pathologic phenotypes of IgA nephropathy. Kidney Int 68:167–172

    Article  CAS  Google Scholar 

  29. Lau KK, Wyatt RJ, Gaber LW (2005) Purpura followed by proteinuria in a 7-year-old girl. Am J Kidney Dis 46:1140–1144

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by National Institutes of Health grants DK57750, DK61525, DK71802, DK78244, and DK64400, by grants to the General Clinical Research Centers of the University of Tennessee Health Sciences Center M01, RR00211, and the University of Alabama at Birmingham M01, RR00032, and by a generous gift to the University of Tennessee Pediatric Nephrology Research Support Fund by Anna and Donald Waite. The authors express their appreciation to Dr. Kimberly Fisher and Sandra Grimes (University of Tennessee) for collecting serum samples and clinical data and to Rose Kulhavy (University of Alabama at Birmingham) for providing the IgA1 myeloma protein. The authors appreciate the technical assistance of Rhubell Brown, Stacy Hall, Candace Kirksey, and Claretha Nichols in the processing of the serum samples.

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Authors and Affiliations

  1. Department of Pediatrics, University of California at Davis, Davis, CA, USA

    Keith K. Lau

  2. Department of Pediatrics, University of Tennessee Health Sciences Center and Children’s Foundation Research Center, Memphis, TN, USA

    Robert J. Wyatt

  3. Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA

    Zina Moldoveanu, Bruce A. Julian, Wen-Qiang Huang, Jiri Mestecky & Jan Novak

  4. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Milan Tomana, Bruce A. Julian, Jeannette Y. Lee & Jiri Mestecky

  5. St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA

    Ronald J. Hogg

  6. Department of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 734, Birmingham, AL, 35294-2170, USA

    Jan Novak

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  1. Keith K. Lau
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  2. Robert J. Wyatt
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  3. Zina Moldoveanu
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  4. Milan Tomana
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  5. Bruce A. Julian
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  7. Jeannette Y. Lee
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  8. Wen-Qiang Huang
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  9. Jiri Mestecky
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  10. Jan Novak
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Correspondence to Jan Novak.

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Lau, K.K., Wyatt, R.J., Moldoveanu, Z. et al. Serum levels of galactose-deficient IgA in children with IgA nephropathy and Henoch-Schönlein purpura. Pediatr Nephrol 22, 2067–2072 (2007). https://doi.org/10.1007/s00467-007-0623-y

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  • DOI: https://doi.org/10.1007/s00467-007-0623-y

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