Şükrü ÇEKİÇ, Gülcan ÜNER, Sara Şebnem GÜLTEKİN KILIÇ

Hiperimmünglobulin M Sendromu

Hiperimmünglobulin M sendromu, IgG, IgA ve IgE düzeylerinde belirgin azalmagörülürken serum IgM düzeyinin yüksek veya normal olması ile karakterizebir primer immün yetmezlik tablosudur. Tekrarlayan piyojenik enfeksiyonlar,IgM antikorları tarafından oluşturulan otoimmün bozukluklar ve IgM üreten Bhücrelerinin malign lenfoproliferatif hastalıklarına yatkınlık söz konusudur.Tedavide 3-4 haftada aralıklarla intravenöz immünoglobulin verilmesi etkindir.P. jirovecii profilaksisi için trimetoprim-sulfametoksazol kullanılır, nötropenivarlığında seçilmiş hastalarda granülosit koloni stimülan faktör (G-CSF) tedavisiönerilmektedir. Kemik iliği veya kordon kanı nakli kür sağlayabilen tedaviseçenekleridir. (Gün cel Pe di at ri 2014;2:81-7)

Hyperimmunglobulin M Syndrome

Hyperimmunoglobulin M syndrome is a primary immune deficiency characterizedby increased or normal levels of serum IgM with clearly decreased serum IgG,IgA and IgE levels. Patients affected with hiper IgM syndrome are susceptibleto recurrent pyogenic infections, to autoimmune diseases induced by IgMantibodies and to malignant lymphoproliferative disease IgM producing B cells.Intravenous immunoglobulin replacement for therapy every 3-4 weeks is effective.Prophylactic treatment for P. jirovecii on trimethoprim-sulfhamethoxazole, inselected neutropenic patients granulocyte colony stimulated factor (G-CSF)treatment is suggested. Bone marrow or cord blood transplantation may providecure for this syndrome. (The Jo ur nal of Cur rent Pe di at rics 2014;2:81-7)

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1. Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev 1992;3:101-21.
2. Burtin P. Un exemple dagammaglobulinemia atypique (uncas de grande hypogammaglobulinemia avec augmentation de β-2macroglobuline). Pev Franc Etud Clin Biol 1961;6:286-9.
3. Rosen FS, Kevy SV, Merler E, Janeway CA, Gitlin D. Recurrent bacterial infections and dysgammaglobulinemia; deficiency of 7S gammaglobulins in the presence of elevated 19S gammaglobulins. Pediatrics 1961;28:182.
4. Etzioni A, Ochs HD. The Hyper IgM Syndrome-An Evolving Story. Pediatric research 2004;56:510-24.
5. Ersoy F, Sanal O, Tezcan I. Clinical and immunological aspects of hyper-IgM syndrome. Turk J Pediatr 1990;32:13-20.
6. Orange JS, Levy O, Geha RS. Human disease resulting from gene mutations that interfere with appropriate nuclear factor- kappa B activation. Immunol Rev 2005;203:21-37.
7. Davies EG, Thrasher AJ. Update on the hyper immunoglobulin M syndromes Blackwell Publishing Ltd. Br J Haematol 2010;149:167-80.
8. Kracker S, Gardes P, Mazerolles F, Durandy A. Immunoglobulin class switch recombination deficiencies. Clinical Immunology 2010;135:193-203.
9. Geha RS, Plebani A, Notarengelo LD. CD40, CD40 Ligand and the Hyper IgM Syndrome. Primary Immunodeficiency Diseases: a molecular and genetic approach/edited by Ochs HD, Smith CIE, Puck JM. 2nd ed. 251-268.
10. Levy J, Espanol-Boren T, Thomas C, Fischer A, Tovo P, Bordigoni P, et al. Clinical spectrum of X-linked hyper-IgM syndrome. The Journal of Pediatrics 1997;131:47-54.
11. Agematsu K, Nagumo H, Shinozaki K, Hokibara S, Yasui K, et al. Absence of IgD-CD27(+) memory B cell population in X-linked hyper-IgM syndrome. J Clin Invest 1998;102:853-60.
12. Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, et al. The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. Medicine (Baltimore) 2003;82:373-84.
13. Subauste CS, Wessendarp M, Sorensen RU, Leiva LE. CD40- CD40 ligand interaction is central to cell-mediated immunity against Toxoplasma gondii: patients with hyper IgM syndrome have a defective type 1 immune response that can be restored by soluble CD40 ligand trimer. j immunol 1999;162:6690-700.
14. Hayashi T, Rao SP, Meylan PR, Kornbluth RS, Catanzaro A. Role of CD40 ligand in Mycobacterium avium infection. Infection and Immunity 1999;67:3558-65.
15. Hayward AR, Levy J, Facchetti F, Notarangelo L, Ochs HD, Etzioni, A et al. Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM. J Immunol 1997;158:977-83.
16. Revy P, Muto T, Levy Y, Geissmann F, Plebani A, Sanal O, et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 2000;102:565-75.
17. Quartier P, Bustamante J, Sanal O, Plebani A, Debre M, Deville A, et al. Clinical, immunologic and genetic analysis of 29 patients with autosomal recessive hyper-IgM syndrome due to Activation-Induced Cytidine Deaminase deficiency. Clinical Immunology 2004;110:22-9.
18. Ta VT, Nagaoka H, Catalan N, Durandy A, Fischer A, Imai K, et al. AID mutant analyses indicate requirement for class-switch- specific cofactors. Nature Immunology 2003;4:843-8.
19. Hase K, Takahashi D, Ebisawa M, Kawano S, Itoh K, Ohno H. Activation-induced cytidine deaminase deficiency causes organ- specific autoimmune disease. Plos One 2008;3:3033.
20. Meyers G, Ng YS, Bannock JM, Lavoie A, Walter JE, Notarangelo LD, et al. Activation-induced cytidine deaminase (AID) is required for B-cell tolerance in humans. Proc Natl Acad Sci USA 2011;108:11554-9.
21. Ferrari S, Giliani S, Insalaco A, Al-Ghonaium A, Soresina AR, Loubser M, et al. Mutasyon of CD40 gene causes an autosomal form of immun deficiency with hiper IgM. Proc Natl Acad Sci USA 2001;98:12614-9.
22. Kutukculer N, Aksoylar S, Kansoy S, Cetingul N, Notarangelo LD. Outcome of hematopoietic stem cell transplantataion in hiper IgM syndrome caused by CD40 deficiency. J Pediatr 2003;143:141-2.
23. Imai K, Slupphaug G, Lee WI, Revy P, Nonoyama S, Catalan N, et al. Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat Immunol 2003;4:945-6.
24. Clarke A, Phillips DI, Brown R, Harper PS. Clinical aspects of X-linked hypohidrotic ectodermal dysplasia. Arch Dis Child 1987;62:989-96.
25. Abinun M, Spickett G, Appleton AL, Flood T, Cant AJ. Anhidrotic ectodermal dysplasia associated with specific antibody deficiency. Eur J Pediatr 1996;155:146-7.
26. Carrol ED, Gennery AR, Flood TJ, Spickett GP, Abinun M. Anhidrotic ectodermal dysplasia and immunodeficiency: the role of NEMO. Arch Dis Child 2003;88:340-1.
27. Orange JS, Geha RS. Finding NEMO: genetic disorders of NF- κB activation. J Clin Invest 2003;112:983-5.
28. Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, et al. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO) Am J Hum Genet 2000;67:1555-62.
29. Dimicoli S, Bensoussan D, Latger-Cannard V, Straczek J, Antunes L, Mainard L, et al. Complete recovery from cryptosporidium parvum infection with gastroenteritis and sclerosing cholangitis after successful bone marrow transplantation in two brothers with X-linked hyper-IgM syndrome. Bone Marrow Transplant 2003;32:733-7.
30. Gennery AR, Khawaja K, Veys P, Bredius RG, Notarangelo LD, Mazzolari E, et al. Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993-2002. Blood 2004;103:1152-7.
31. McLauchlin J, Amar CF, Pedraza-Díaz S, Mieli-Vergani G, Hadzic N, Davies EG. Polymerase chain reaction-based diagnosis of infection with Cryptosporidium in children with primary immunodeficiencies. Pediatr Infect Dis J 2003;22:329- 35.