Immune-Mediated Diseases pp 27-36
Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Inheritance: Model for Autoaggression
Patients with the rare X-linked syndrome, immune dysregulation, polyendocrinopathy, enteropathy (IPEX) may present early in life with type I diabetes, hyperthyroidism, chronic enteropathy, villous atrophy, dermatitis, autoimmune hemolytic anemia, and antibody- induced neutropenia and thrombocytopenia. Of the reported families with IPEX, most affected boys died before the age of 3 years of malabsorbtion, failure to thrive, infections, or other complications. Characteristic findings at autopsy include lymphocytic infiltrates affecting the lungs, endocrine organs, such as pancreas and thyroid and skin, and increased lymphoid elements in lymph nodes and spleen. Although symptomatic therapy with immunosuppressive drugs provides some beneficial effects, the only curative treatment is hematopoietic stem cell transplantation.
Unable to display preview. Download preview PDF.
- Baud, O., Goulet, O., Canioni, D., Le Deist, F., Radford, I., Rieu, D., Dupuis-Girod, S., Cerf-Bensussan, N., Cavazzana-Calvo, M., Brousse, N., Fischer, A. and Casanova, J.L. (2001) Treatment of the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) by allogeneic bone marrow transplantation. N. Engl. J. Med. 344, 1758–1762.CrossRefPubMedGoogle Scholar
- Bennett, C.L., Christie, J., Ramsdell, F., Brunkow, M.E., Ferguson, P.J., Whitesell, L., Kelly, T.E., Saulsbury, F.T., Chance, P.F. and Ochs, H.D. (2001b) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27, 20–21.CrossRefPubMedGoogle Scholar
- Brunkow, M.E., Jeffery, E.W., Hjerrild, K.A., Paeper, B., Clark, L.B., Yasayko, S.A., Wilkinson, J.E., Galas, D., Ziegler, S.F. and Ramsdell, F. (2001) Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 27, 68–73.CrossRefPubMedGoogle Scholar
- Gambineri, E., Torgerson, T.R. and Ochs, H.D. (2003) Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T cell homeostasis. Curr. Opin. Rheumatol. 15, 430–435.CrossRefPubMedGoogle Scholar
- Itoh, M., Takahashi, T., Sakaguchi, N., Kuniyasu, Y., Shimizu, J., Otsuka, F. and Sakaguchi, S. (1999) Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J. Immunol. 162, 5317–5326.PubMedGoogle Scholar
- Nieves, D.S., Phipps, R.P., Pollock, S.J., Ochs, H.D., Zhu, Q., Scott, G.A., Ryan, C.K., Kobayashi, I., Rossi, T.M. and Goldsmith, L.A. (2004) Dermatologic and immunologic findings in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Arch. Dermatol. 140, 466–472.CrossRefPubMedGoogle Scholar
- Wildin, R.S., Ramsdell, F., Peake, J., Faravelli, F., Casanova, J.L., Buist, N., Levy-Lahad, E., Mazzella, M., Goulet, O., Perroni, L., Bricarelli, F.D., Byrne, G., McEuen, M., Proll, S., Appleby, M. and Brunkow, M.E. (2001) X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 27, 18–20.CrossRefPubMedGoogle Scholar
- Zorn, E., Kim, H.T., Lee, S.J., Floyd, B.H., Litsa, D., Arumugarajah, S., Bellucci, R., Alyea, E.P., Antin, J.H., Soiffer, R.J. and Ritz, J. (2005) Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease. Blood 106, 2903–2911.CrossRefPubMedGoogle Scholar