Use of Sirolimus in IPEX and IPEX-Like Children
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IPEX (immune dysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome), a rare inflammatory disease caused by mutations of Foxp3, destroys the immunoregulatory environment of affected male infants. Data on optimal therapy are limited.
We reviewed the effect of sirolimus use in our cohort of IPEX and IPEX-like patients (n = 7).
Results and Discussion
Our patients exhibited features of enteropathy and recurrent infections with bacterial and viral pathogens. Before initiating sirolimus, six patients were treated with corticosteroids. Several also received other immunosuppressive agents. After starting sirolimus, six patients had improvement in diarrhea, and two were able to decrease corticosteroid dosages. Several also had significantly decreased number of infections after treatment. Of the three patients with post-treatment duodenal biopsies, two showed improvement in villous architecture. No significant adverse events occurred. Our experience suggests that sirolimus is a clinically effective and safe therapeutic option in IPEX and IPEX-like patients.
- Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001;27:20–1. CrossRef
- Torgerson TR, Ochs HD. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: forkhead box protein 3 mutations and lack of regulatory T cells. J All Clin Immunol. 2007;120:744–50. CrossRef
- Caudy AA, Reddy ST, Chatila T, Atkinson JP, Verbsky JW. CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome and defective IL-10 expression from CD4 lymphocytes. J Allergy Clin Immunol. 2007;119:482–7. CrossRef
- Baud O, Goulet O, Canioni D, LeDeist F, Radford I, Rieu D, et al. Treatment of IPEX by allogeneic BMT. NEJM. 2001;344:1758–62. CrossRef
- Mazzolari E, Forino C, Fontana M, Ippolito CD, Lanfranchi A, Gambineri E, Ochs H, Badolato R, Notarangelo LD. A new case of IPEX receiving bone marrow transplantation. Bone Marrow Transplant. 2005;35:1033–4. CrossRef
- Rao A, Kamani N, Filipovich A, Lee SM, Davies SM, Dalal J, et al. Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning. Blood. 2007;109(1):383–5. CrossRef
- Powell BR, Buist NRM, Stenzel P. An X-linked syndrome of diarrhea, polyendocrinopathy, and fatal infection in infancy. J Pediatr. 1982;100:731–7. CrossRef
- DiRocco M, Marta R. X-linked immune deregulation, neonatal insulin-dependent diabetes, and intractable diarrhoea. Arch Dis Child. 1996;75:F143.
- Ellis D, Fisher SE, Smith WI, Jaffe R. Familial occurrence of renal and interstitial disease associated with tissue autoantibodies. Am J Dis Child. 1982;136:323–6.
- Peake JE, McCrossin RB, Byrne G, Shepherd R. X-linked immune dysregulation, neonatal insulin dependent diabetes, and intractable diarrhoea. Arch Dis Child. 1996;74:F195–9. CrossRef
- Mirakian R, Richardson A, Milla PJ, Walker-Smith JA, Unsworth J, Savage MO, et al. Protracted diarrhoea of infancy: evidence in support of an autoimmune variant. BMJ. 1986;293:1132–6.
- Savage MO, Mirakian R, Harries JT, Bottazzo GF. Could protracted diarhoea of infancy have an autoimmune pathogenesis? Lancet. 1982;i:966–7. CrossRef
- Walker-Smith JA, Unsworth DJ, Hutchins P, Phillips AD, Holborow EJ. Autoantibodies against gut epithelium in child with small-intestinal enteropathy. Lancet. 1982;i:566–7. CrossRef
- Ferguson PJ, Blanton SH, Saulsbury FT, McDuffie MJ, Lemahieu V, Gastier JM, et al. Manifestations and linkage analysis in X-linked autoimmunity-immunodeficiency syndrome. Am J Med Gen. 2000;90:390–7. CrossRef
- Levy-Lahad E, Wildin RS. Neonatal diabetes mellitus, enteropathy, thrombocytopenia, and endocrinopathy: further evidence for an X-linked lethal syndrome. J Pediatr. 2001;138:577–80. CrossRef
- Bousvaros A, Leichtner AM, Book L, Shigeoka A, Bilodeau J, Semeao E, et al. Treatment of pediatric autoimmune enteropathy with tacrolimus. Gastroenterology. 1996;111:237–43. CrossRef
- Kobayashi I, Nakanishi M, Okano M, Sakiyama Y, Matsumoto S. Combination therapy with tacrolimus and betamethasone for a patient with X-linked auto-immune enteropathy. Eur J Pediatr. 1995;154:594–5. CrossRef
- Wildin RS, Smyk-Pearson S, Filipovich AH. Clinical and molecular features of the IPEX syndrome. J Med Genet. 2002;39:537–45. CrossRef
- Napoli KL, Taylor PJ. From beach to bedside: history of the development of sirolimus. Ther Drug Monit. 2001;23:559–86. CrossRef
- Sousa JE, Costa MA, Sousa AGMR, Abizaid AC, Seixas AC, Abizid AS, et al. Two-year angiographic and intravascular ultrasound follow-up after implantation of sirolimus-eluting stents in human coronary arteries. Circulation. 2003;107:381–3. CrossRef
- Battaglia M, Stabilini A, Migliavacca B, Jorejs-Joeck J, Kaupper T, Roncarolol MG. Rapamycin promotes expansion of function CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol. 2006;177:8338–47.
- Coenen JJA, Koenin HJPM, van Rijssen E, Kasran A, Boon L, Hilbrandds LB, et al. Rapamycin, not cyclosporine, permits thymic generation and peripheral preservation of CD4+CD25+FoxP3+ T cells. Bone Marrow Transplant. 2007;39:537–45. CrossRef
- Bindl L, Torgerson T, Perroni L, Youssef N, Ochs HD, Goulet O, et al. Successful use of the new immune-suppressor sirolimus in IPEX. J Pediatr. 2005;147:256–9. CrossRef
- Owen CJ, Jenings CE, Imrie H, Lachaux A, Bridges NA, Cheetham TD, et al. Mutational analysis of the FOXP3 gene and evidence for genetic heterogeneity in the immunodysregulation, polyendocrinopathy, enteropathy syndrome. J Clin Endocrinol Metab. 2003;88:6034–9. CrossRef
- Use of Sirolimus in IPEX and IPEX-Like Children
Journal of Clinical Immunology
Volume 28, Issue 5 , pp 581-587
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- Author Affiliations
- 1. Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA
- 2. Division of Pulmonary, Allergy and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
- 5. Robert Wood Johnson Clinical Scholars Program, University of Pennsylvania School of Medicine, 423 Guardian Drive, 1303A Blockley Hall, Philadelphia, PA, 19104, USA
- 3. Division of Pathology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
- 4. Division of Allergy and Immunology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA