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Autoimmune lymphoproliferative syndrome presenting with glomerulonephritis

Abstract.

Autoimmune lymphoproliferative syndrome (ALPS) is characterized clinically by chronic non-malignant lymphoproliferation and autoimmunity and is caused by a genetic defect in programmed cell death (apoptosis). Most patients with ALPS have heterozygous mutations in the Fas gene. We describe an 11-year-old Brazilian boy with hepatosplenomegaly, lymphadenopathy, hemolytic anemia, and hypergammaglobulinemia since early infancy. T cell lines from the patient were defective in Fas-mediated apoptosis. He was diagnosed as having ALPS and found to have a novel Fas gene mutation (IVS4+1G>A). In addition, he presented with glomerulonephritis in infancy. An aunt and uncle who had the same Fas mutations also had histories of glomerulonephritis. Although glomerulonephritis is common in Fas-deficient mice, it is infrequent in human ALPS. Corticosteroid therapy ameliorated the glomerulonephritis in our patient, as well as his lymphoproliferation, anemia, and hypergammaglobulinemia. This study suggests that glomerulonephritis is one of the characteristic features of ALPS.

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References

  1. 1.

    Sneller MC, Straus SE, Jaffe ES, Jaffe JS, Fleisher TA, Stetler-Stevenson M, Strober W (1992) A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease. J Clin Invest 90:334–341

    CAS  PubMed  Google Scholar 

  2. 2.

    Fisher GH, Rosenberg FJ, Straus SE, Dale JK, Middelton LA, Lin AY, Strober W, Lenardo MJ, Puck JM. (1995) Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 81:935–946

    CAS  PubMed  Google Scholar 

  3. 3.

    Rieux-Laucat F, Le Deist F, Hivroz C, Roberts AG, Debatin KM, Fischer A, Villartay JP de (1995) Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science 268:1347–1349

    CAS  PubMed  Google Scholar 

  4. 4.

    Wu J, Wilson J, He J, Xiang L, Schur PH, Mountz JD (1996) Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease. J Clin Invest 98:1107–1113

    CAS  PubMed  Google Scholar 

  5. 5.

    Wang J, Zheng L, Lobito A, Chan FK, Dale J, Sneller M Yao X, Puck JM, Straus SE, Lenardo MJ (1999) Inherited human caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Cell 98:47–58

    CAS  PubMed  Google Scholar 

  6. 6.

    Jackson CE, Puck JM (1999) Autoimmune lymphoproliferative syndrome, a disorder of apoptosis. Curr Opin Pediatr 11:521–527

    CAS  PubMed  Google Scholar 

  7. 7.

    Kasahara Y, Wada T, Niida Y, Yachie A, Seki H, Ishida Y, Sakai T, Koizumi F, Koizumi S, Miyawaki T, Taniguchi N (1998) Novel Fas (CD95/APO-1) mutations in infants with a lymphoproliferative disorder. Int Immunol 10:195–202

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Infante AJ, Britton HA, DeNapoli T, Middelton LA, Lenardo MJ, Jackson CE, Wang J, Fleisher T, Straus SE, Puck JM (1998) The clinical spectrum in a large kindred with autoimmune lymphoproliferative syndrome caused by a Fas mutation that impairs lymphocyte apoptosis. J Pediatr 133:629–633

    CAS  PubMed  Google Scholar 

  9. 9.

    Jackson CE, Fisher RE, Hsu AP, Anderson SM, Choi Y, Wang J, Dale JK, Fleisher TA, Middelton LA, Sneller MC, Lenardo MJ, Straus SE, Puck JM (1999) Autoimmune lymphoproliferative syndrome with defective Fas: genotype influences penetrance. Am J Hum Genet 64:1002–1014

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Vaishnaw AK, Toubi E, Ohsako S, Drappa J, Buys S, Estrada J, Sitarz A, Zemel L, Chu JL, Elkon KB (1999) The spectrum of apoptosis defects and clinical manifestations, including systemic lupus erythematosus, in humans with CD95 (Fas/APO-1) mutations. Arthritis Rheum 42:1833–1842

    CAS  PubMed  Google Scholar 

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Acknowledgements.

We are grateful to Mr. Hitoshi Moriuchi and Ms. Chikako Sakai for technical assistance. This study was supported by grants from the Japan International Cooperation Agency, the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Ministry of Health, Labour, and Welfare of Japan, the Naito Foundation, and The Mother and Child Health Foundation.

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Correspondence to Hirokazu Kanegane.

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Kanegane, H., Vilela, M.M.S., Wang, Y. et al. Autoimmune lymphoproliferative syndrome presenting with glomerulonephritis. Pediatr Nephrol 18, 454–456 (2003). https://doi.org/10.1007/s00467-003-1087-3

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Keywords

  • Autoimmune lymphoproliferative syndrome
  • Fas
  • Apoptosis
  • Glomerulonephritis
  • Brazil