Immune Dysregulation may lead to severe autoimmune manifestations and/or excessive inflammatory response. These may be due to lack of appropriate T cell education in the thymus resulting in an Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy( APECED) syndrome (1,2), lack of regulatory T cells resulting in immune dysregulation, polyendocrinopathy, enetropathy (IPEX) syndrome(3,4), syndromes of immunodeficiency with hypopigementation including Chediac Higashi syndrome, Gricelli and Hermansky-Pudlak syndrome (5-7), familial hemophagocytic lymphohistiocytosis syndromes due to abnormal vescicle trafficking and/or fusion with reduced cytolitic activity(8) and abnormalities of apoptosis leading to autoimmune lymphoproliferative syndrome(ALPS)(9).

1. Abramson J, Giraud M, Benoist C, Mathis D. Aire's partners in the molecular control of immunological tolerance. Cell 2010;140:123-135.

2. Kisand K, Boe Wolff AS, Podkrajsek KT, Tserel L, Link M, Kisand KV et al. Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J Exp Med 2010;207:299-308.

3. Blanco QA, Arranz SE, Bernardo OD, Garrote Adrados JA. From autoimmune enteropathy to the IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X-linked) syndrome. Allergol Immunopathol (Madr ) 2009;37:208-215.

4. d'Hennezel E, Ben Shoshan M, Ochs HD, Torgerson TR, Russell LJ, Lejtenyi C et al. FOXP3 forkhead domain mutation and regulatory T cells in the IPEX syndrome. N Engl J Med 2009;361:1710-1713.

5. Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A et al. Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. J Allergy Clin Immunol 2007;120:776-794.

6. Manoli I, Golas G, Westbroek W, Vilboux T, Markello TC, Introne W et al. Chediak-Higashi syndrome with early developmental delay resulting from paternal heterodisomy of chromosome 1. Am J Med Genet A 2010;152A:1474-1483.

7. Dessinioti C, Stratigos AJ, Rigopoulos D, Katsambas AD. A review of genetic disorders of hypopigmentation: lessons learned from the biology of melanocytes. Exp Dermatol 2009;18:741-749.

8. Gupta S, Weitzman S. Primary and secondary hemophagocytic lymphohistiocytosis: clinical features, pathogenesis and therapy. Expert Rev Clin Immunol 2010;6:137-154.

9. Randhawa SR, Chahine BG, Lowery-Nordberg M, Cotelingam JD, Casillas AM. Underexpression and overexpression of Fas and Fas ligand: a double-edged sword. Ann Allergy Asthma Immunol 2010;104:286-292.