Autoimmunity is often observed among individuals with primary immune deficiencies; however, the frequency and role of autoimmunity in Schimke immuno-osseous dysplasia (SIOD) has not been fully assessed. SIOD, which is caused by mutations of SMARCAL1, is a rare autosomal recessive disease with its prominent features being skeletal dysplasia, T cell deficiency, and renal failure. We present a child with severe SIOD who developed rituximab resistant Evans syndrome (ES). Consistent with observations in several other immunodeficiency disorders, a review of SIOD patients showed that approximately a fifth of SIOD patients have some features of autoimmune disease. To our best knowledge this case represents the first patient with SIOD and rituximab resistant ES and the first study of autoimmune disease in SIOD.

Department of Pediatrics 2nd Faculty of Medicine Charles University University Hospital Motol Prague Czech Republic

See more in PubMed

Evans RS, Takahashi K, Duane RT, Payne R, Liu C. Primary thrombocytopenic purpura and acquired hemolytic anemia; evidence for a common etiology. AMA Arch Intern Med. 1951;87:48–65. PubMed

Deleze M, Oria CV, Alarcon-Segovia D. Occurrence of both hemolytic anemia and thrombocytopenic purpura (Evans' syndrome) in systemic lupus erythematosus. Relationship to antiphospholipid antibodies. J Rheumatol. 1988;15:611–615. PubMed

Garcia-Munoz R, Rodriguez-Otero P, Pegenaute C, Merino J, Jakes-Okampo J, Llorente L, Bendandi M, Panizo C. Splenic marginal zone lymphoma with Evans' syndrome, autoimmunity, and peripheral gamma/delta T cells. Ann Hematol. 2009;88:177–178. doi: 10.1007/s00277-008-0555-z. PubMed DOI

Hauswirth AW, Skrabs C, Schutzinger C, Raderer M, Chott A, Valent P, Lechner K, Jager U. Autoimmune thrombocytopenia in non-Hodgkin's lymphomas. Haematologica. 2008;93:447–450. doi: 10.3324/haematol.11934. PubMed DOI

Michel M, Chanet V, Galicier L, Ruivard M, Levy Y, Hermine O, Oksenhendler E, Schaeffer A, Bierling P, Godeau B. Autoimmune thrombocytopenic purpura and common variable immunodeficiency: analysis of 21 cases and review of the literature. Medicine (Baltimore) 2004;83:254–263. doi: 10.1097/01.md.0000133624.65946.40. PubMed DOI

Carneiro-Sampaio M, Coutinho A. Tolerance and autoimmunity: lessons at the bedside of primary immunodeficiencies. Adv Immunol. 2007;95:51–82. PubMed

Westerberg LS, Klein C, Snapper SB. Breakdown of T cell tolerance and autoimmunity in primary immunodeficiency--lessons learned from monogenic disorders in mice and men. Curr Opin Immunol. 2008;20:646–654. doi: 10.1016/j.coi.2008.10.004. PubMed DOI PMC

Agarwal S, Cunningham-Rundles C. Autoimmunity in common variable immunodeficiency. Curr Allergy Asthma Rep. 2009;9:347–352. doi: 10.1007/s11882-009-0051-0. PubMed DOI PMC

Coutinho A, Carneiro-Sampaio M. Primary immunodeficiencies unravel critical aspects of the pathophysiology of autoimmunity and of the genetics of autoimmune disease. J Clin Immunol. 2008;28(Suppl 1):S4–10. PubMed

Lehman HK, Ballow M. Immune deficiency disorders with autoimmunity and abnormalities in immune regulation-monogenic autoimmune diseases. Clin Rev Allergy Immunol. 2008;34:141–145. doi: 10.1007/s12016-007-8038-x. PubMed DOI

Torgerson TR. Immune dysregulation in primary immunodeficiency disorders. Immunol Allergy Clin North Am. 2008;28:315–327. doi: 10.1016/j.iac.2008.02.002. viii-ix. PubMed DOI

Spranger J, Hinkel GK, Stoss H, Thoenes W, Wargowski D, Zepp F. Schimke immuno-osseous dysplasia: a newly recognized multisystem disease. J Pediatr. 1991;119:64–72. doi: 10.1016/S0022-3476(05)81040-6. PubMed DOI

Schimke RN, Horton WA, King CR. Chondroitin-6-sulphaturia, defective cellular immunity, and nephrotic syndrome. Lancet. 1971;2:1088–1089. PubMed

Ehrich JH, Burchert W, Schirg E, Krull F, Offner G, Hoyer PF, Brodehl J. Steroid resistant nephrotic syndrome associated with spondyloepiphyseal dysplasia, transient ischemic attacks and lymphopenia. Clin Nephrol. 1995;43:89–95. PubMed

Boerkoel CF, O'Neill S, Andre JL, Benke PJ, Bogdanovic R, Bulla M, Burguet A, Cockfield S, Cordeiro I, Ehrich JH. et al.Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and a review of the literature. Eur J Pediatr. 2000;159:1–7. doi: 10.1007/s004310050001. PubMed DOI

Kaitila I, Savilahti E, Ormala T. Autoimmune enteropathy in Schimke immunoosseous dysplasia. Am J Med Genet. 1998;77:427–430. doi: 10.1002/(SICI)1096-8628(19980605)77:5<427::AID-AJMG14>3.0.CO;2-K. PubMed DOI

Kilic SS, Donmez O, Sloan EA, Elizondo LI, Huang C, Andre JL, Bogdanovic R, Cockfield S, Cordeiro I, Deschenes G. et al.Association of migraine-like headaches with Schimke immuno-osseous dysplasia. Am J Med Genet A. 2005;135:206–210. PubMed

Ehrich JH, Offner G, Schirg E, Hoyer PF, Helmchen U, Brodehl J. Association of spondylo-epiphyseal dysplasia with nephrotic syndrome. Pediatr Nephrol. 1990;4:117–121. doi: 10.1007/BF00858821. PubMed DOI

Hashimoto K, Takeuchi A, Ieshima A, Takada M, Kasagi M. Juvenile variant of Schimke immunoosseous dysplasia. Am J Med Genet. 1994;49:266–269. doi: 10.1002/ajmg.1320490304. PubMed DOI

Clewing JM, Fryssira H, Goodman D, Smithson SF, Sloan EA, Lou S, Huang Y, Choi K, Lucke T, Alpay H. et al.Schimke immunoosseous dysplasia: suggestions of genetic diversity. Hum Mutat. 2007;28:273–283. doi: 10.1002/humu.20432. PubMed DOI

Boerkoel CF, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L, Andre JL, Bogdanovic R, Burguet A, Cockfield S. et al.Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia. Nat Genet. 2002;30:215–220. doi: 10.1038/ng821. PubMed DOI

Bansbach CE, Betous R, Lovejoy CA, Glick GG, Cortez D. The annealing helicase SMARCAL1 maintains genome integrity at stalled replication forks. Genes Dev. 2009;23:2405–2414. doi: 10.1101/gad.1839909. PubMed DOI PMC

Driscoll R, Cimprich KA. HARPing on about the DNA damage response during replication. Genes Dev. 2009;23:2359–2365. doi: 10.1101/gad.1860609. PubMed DOI PMC

Yusufzai T, Kong X, Yokomori K, Kadonaga JT. The annealing helicase HARP is recruited to DNA repair sites via an interaction with RPA. Genes Dev. 2009;23:2400–2404. doi: 10.1101/gad.1831509. PubMed DOI PMC

Ciccia A, Bredemeyer AL, Sowa ME, Terret ME, Jallepalli PV, Harper JW, Elledge SJ. The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart. Genes Dev. 2009;23:2415–2425. doi: 10.1101/gad.1832309. PubMed DOI PMC

Postow L, Woo EM, Chait BT, Funabiki H. Identification of SMARCAL1 as a component of the DNA damage response. J Biol Chem. 2009. PubMed PMC

Morimoto M, Cho K-S, Myung C, Shaw CA, Beirnes K, Leung D, Fam H-K, Choi K, Huang Y, Huang C, Schimke immuno-osseous dysplasia: a disorder of transcriptional responses to cell signaling? Submitted. 2011.

Hall CM. International nosology and classification of constitutional disorders of bone (2001) Am J Med Genet. 2002;113:65–77. doi: 10.1002/ajmg.10828. PubMed DOI

Ming JE, Stiehm ER, Graham JM Jr. Syndromes associated with immunodeficiency. Adv Pediatr. 1999;46:271–351. PubMed

Brandt D, Gershwin ME. Common variable immune deficiency and autoimmunity. Autoimmun Rev. 2006;5:465–470. doi: 10.1016/j.autrev.2006.03.010. PubMed DOI

Knight AK, Cunningham-Rundles C. Inflammatory and autoimmune complications of common variable immune deficiency. Autoimmun Rev. 2006;5:156–159. doi: 10.1016/j.autrev.2005.10.002. PubMed DOI

Tarr PE, Sneller MC, Mechanic LJ, Economides A, Eger CM, Strober W, Cunningham-Rundles C, Lucey DR. Infections in patients with immunodeficiency with thymoma (Good syndrome). Report of 5 cases and review of the literature. Medicine (Baltimore) 2001;80:123–133. doi: 10.1097/00005792-200103000-00005. PubMed DOI

Jesus AA, Duarte AJ, Oliveira JB. Autoimmunity in hyper-IgM syndrome. J Clin Immunol. 2008;28(Suppl 1):S62–66. PubMed

Dupuis-Girod S, Medioni J, Haddad E, Quartier P, Cavazzana-Calvo M, Le Deist F, de Saint Basile G, Delaunay J, Schwarz K, Casanova JL. et al.Autoimmunity in Wiskott-Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients. Pediatrics. 2003;111:e622–627. doi: 10.1542/peds.111.5.e622. PubMed DOI

Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA. A multiinstitutional survey of the Wiskott-Aldrich syndrome. J Pediatr. 1994;125:876–885. doi: 10.1016/S0022-3476(05)82002-5. PubMed DOI

Zonios DI, Falloon J, Bennett JE, Shaw PA, Chaitt D, Baseler MW, Adelsberger JW, Metcalf JA, Polis MA, Kovacs SJ. et al.Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors. Blood. 2008;112:287–294. doi: 10.1182/blood-2007-12-127878. PubMed DOI PMC

Elizondo LI, Huang C, Northrop JL, Deguchi K, Clewing JM, Armstrong DL, Boerkoel CF. Schimke immuno-osseous dysplasia: a cell autonomous disorder? Am J Med Genet A. 2006;140:340–348. PubMed

Petty EM, Yanik GA, Hutchinson RJ, Alter BP, Schmalstieg FC, Levine JE, Ginsburg D, Robillard JE, Castle VP. Successful bone marrow transplantation in a patient with Schimke immuno- osseous dysplasia. J Pediatr. 2000;137:882–886. doi: 10.1067/mpd.2000.109147. PubMed DOI

Ludman MD, Cole DE, Crocker JF, Cohen MM Jr. Schimke immuno-osseous dysplasia: case report and review. Am J Med Genet. 1993;47:793–796. doi: 10.1002/ajmg.1320470538. PubMed DOI

Schimke immunoosseous dysplasia: an ultra-rare disease. a 20-year case series from the tertiary hospital in the Czech Republic

Low renal but high extrarenal phenotype variability in Schimke immuno-osseous dysplasia