Autoimmune and other cytopenias in primary immunodeficiencies: Pathomechanisms, novel differential diagnoses, and treatment

Blood

Volumn 124, Issue 15, 2014, Pages 2337-2344

  Seidel, Markus G ^a  

^a MEDICAL UNIVERSITY OF GRAZ   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATED PI3KD SYNDROME; APLASTIC ANEMIA; AUTOIMMUNE DISEASE; AUTOIMMUNE HEMOLYTIC ANEMIA; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; BONE MARROW DEPRESSION; BONE MARROW SUPPRESSION; CD27 DEFICIENCY; CD27 DEFICIENCY, LIPOPOLYSACCHARIDE-RESPONSIVE BEIGE LIKE ANCHOR DEFICIENCY; COMMON VARIABLE IMMUNODEFICIENCY; CYTOPENIA; DIFFERENTIAL DIAGNOSIS; GENOTYPE; HUMAN; IMMUNE DEFICIENCY; IMMUNE DYSREGULATION; IMMUNOSUPPRESSIVE TREATMENT; LYMPHOPROLIFERATIVE DISEASE; MONOMAC SYNDROME; PHENOTYPE; REVIEW; SYNDROME; SYSTEMIC LUPUS ERYTHEMATOSUS; THROMBOCYTOPENIA; X LINKED IMMUNODEFICIENCY WITH MAGNESIUM DEFECT; ANIMAL; AUTOIMMUNE DISEASES; IMMUNOLOGIC DEFICIENCY SYNDROMES; IMMUNOLOGY;

ANIMALS; AUTOIMMUNE DISEASES; DIAGNOSIS, DIFFERENTIAL; HUMANS; IMMUNOLOGIC DEFICIENCY SYNDROMES;

EID: 84907637722     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2014-06-583260     Document Type: Review

References (92)

1. Bousfiha AA, Jeddane L, Ailal F, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. J Clin Immunol. 2013;33(6):1078-1087.
2. Parvaneh N, Casanova JL, Notarangelo LD, Conley ME. Primary immunodeficiencies: a rapidly evolving story. J Allergy Clin Immunol. 2013;131(2):314-323.
3. Al-Herz W, Bousfiha A, Casanova JL, et al. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol. 2014;5:162.
4. Vilboux T, Lev A, Malicdan MC, et al. A congenital neutrophil defect syndrome associated with mutations in VPS45. N Engl J Med. 2013;369(1):54-65.
5. Skokowa J, Steinemann D, Katsman-Kuipers JE, et al. Cooperativity of RUNX1 and CSF3R mutations in severe congenital neutropenia: a unique pathway in myeloid leukemogenesis. Blood. 2014;123(14):2229-2237.
6. Boztug K, Klein C. Genetic etiologies of severe congenital neutropenia. Curr Opin Pediatr. 2011;23(1):21-26.
7. Meffre E. The establishment of early B cell tolerance in humans: lessons from primary immunodeficiency diseases. Ann N Y Acad Sci. 2011;1246:1-10.
8. von Boehmer H, Melchers F. Checkpoints in lymphocyte development and autoimmune disease. Nat Immunol. 2010;11(1):14-20.
9. Podjasek JC, Abraham RS. Autoimmune cytopenias in common variable immunodeficiency. Front Immunol. 2012;3:189.
10. Notarangelo LD. Primary immunodeficiencies (PIDs) presenting with cytopenias. Hematology (Am Soc Hematol Educ Program). 2009;139-143.
11. Teachey DT, Lambert MP. Diagnosis and management of autoimmune cytopenias in childhood. Pediatr Clin North Am. 2013;60(6):1489-1511.
12. Chapel H, Lucas M, Lee M, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112(2):277-286.
13. Warnatz K, Wehr C, Dräger R, et al. Expansion of CD19(hi)CD21(lo/neg) B cells in common variable immunodeficiency (CVID) patients with autoimmune cytopenia. Immunobiology. 2002;206(5):502-513.
14. Wehr C, Kivioja T, Schmitt C, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111(1):77-85.
15. Price S, Shaw PA, Seitz A, et al. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood. 2014;123(13):1989-1999.
16. Rensing-Ehl A, Völkl S, Speckmann C, et al. Abnormally differentiated CD4+ or CD8+ T cells with phenotypic and genetic features of double negative T cells in human Fas deficiency. Blood. 2014;124(6):851-860.
17. Rensing-Ehl A, Warnatz K, Fuchs S, et al. Clinical and immunological overlap between autoimmune lymphoproliferative syndrome and common variable immunodeficiency. Clin Immunol. 2010;137(3):357-365.
18. Alangari A, Alsultan A, Adly N, et al. LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J Allergy Clin Immunol. 2012;130(2):481-488.
19. Burns SO, Zenner HL, Plagnol V, et al. LRBA gene deletion in a patient presenting with autoimmunity without hypogammaglobulinemia. J Allergy Clin Immunol. 2012;130(6):1428-1432.
20. Lopez-Herrera G, Tampella G, Pan-Hammarström Q, et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet. 2012;90(6):986-1001.
21. Davies EG, Thrasher AJ. Update on the hyper immunoglobulin M syndromes. Br J Haematol. 2010;149(2):167-180.
22. Anderson G, Baik S, Cowan JE, et al. Mechanisms of thymus medulla development and function. Curr Top Microbiol Immunol. 2014;373:19-47.
23. Felgentreff K, Perez-Becker R, Speckmann C, et al. Clinical and immunological manifestations of patients with atypical severe combined immunodeficiency. Clin Immunol. 2011;141(1):73-82.
24. Speckmann C, Neumann C, Borte S, et al. Delayed-onset adenosine deaminase deficiency: strategies for an early diagnosis. J Allergy Clin Immunol. 2012;130(4):991-994.
25. Schuetz C, Pannicke U, Jacobsen EM, et al. Lesson from hypomorphic recombination-activating gene (RAG) mutations: Why asymptomatic siblings should also be tested. J Allergy Clin Immunol. 2014;133(4):1211-1215.
26. Henderson LA, Frugoni F, Hopkins G, et al. Expanding the spectrum of recombination-activating gene 1 deficiency: a family with early-onset autoimmunity. J Allergy Clin Immunol. 2013;132(4):969-971.
27. Chen K, Wu W, Mathew D, et al. Autoimmunity due to RAG deficiency and estimated disease incidence in RAG1/2 mutations. J Allergy Clin Immunol. 2014;133(3):880-882.
28. Shaw PJ, Feske S. Regulation of lymphocyte function by ORAI and STIM proteins in infection and autoimmunity. J Physiol. 2012;590(Pt 17):4157-4167.
29. Hauck F, Randriamampita C, Martin E, et al. Primary T-cell immunodeficiency with immunodysregulation caused by autosomal recessive LCK deficiency. J Allergy Clin Immunol. 2012;130(5):1144-1152.
30. Li FY, Chaigne-Delalande B, Su H, Uzel G, Matthews H, Lenardo MJ. XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. Blood. 2014;123(14):2148-2152.
31. Abdollahpour H, Appaswamy G, Kotlarz D, et al. The phenotype of human STK4 deficiency. Blood. 2012;119(15):3450-3457.
32. Angulo I, Vadas O, Garc¸on F, et al. Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage. Science. 2013;342(6160):866-871.
33. Hambleton S, McDonald DO, Morgan NV, et al. Autosomal recessive combined immunodeficiency due to loss of function mutation in tripeptidyl peptidase II. [In: 15th Biennial Meeting European Society for Immunodeficiency (ESID). 2012, Florence, Italy: Springer.] J Clin Immunol. 2012;32:384-385.
34. Massaad MJ, Ramesh N, Geha RS. Wiskott-Aldrich syndrome: a comprehensive review. Ann N Y Acad Sci. 2013;1285:26-43.
35. Balduini CL, Savoia A. Genetics of familial forms of thrombocytopenia. Hum Genet. 2012;131(12):1821-1832.
36. Patel K, Akhter J, Kobrynski L, Benjamin Gathmann MA, Davis O, Sullivan KE; International DiGeorge Syndrome Immunodeficiency Consortium. Immunoglobulin deficiencies: the B-lymphocyte side of DiGeorge Syndrome. J Pediatr. 2012;161(5):950-953.
37. Castiello MC, Bosticardo M, Pala F, et al. Wiskott-Aldrich Syndrome protein deficiency perturbs the homeostasis of B-cell compartment in humans. J Autoimmun. 2014;50:42-50.
38. +T cells with phenotypic and genetic features of double negative T cells in human Fas deficiency. Blood. 2014;124(6):851-860.
39. Buckner JH. Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol. 2010;10(12):849-859.
40. Arumugakani G, Wood PM, Carter CR. Frequency of Treg cells is reduced in CVID patients with autoimmunity and splenomegaly and is associated with expanded CD21lo B lymphocytes. J Clin Immunol. 2010;30(2):292-300.
41. Jang E, Cho WS, Cho ML, et al. Foxp3+ regulatory T cells control humoral autoimmunity by suppressing the development of long-lived plasma cells. J Immunol. 2011;186(3):1546-1553.
42. Passweg JR, Giagounidis AA, Simcock M, et al. Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globulin plus cyclosporine with best supportive care-SAKK 33/99. J Clin Oncol. 2011;29(3):303-309.
43. Yoshimi A, Baumann I, Führer M, et al. Immunosuppressive therapy with anti-thymocyte globulin and cyclosporine A in selected children with hypoplastic refractory cytopenia. Haematologica. 2007;92(3):397-400.
44. Hasegawa D, Manabe A, Yagasaki H, et al Japanese Childhood MDS Study Group. Treatment of children with refractory anemia: the Japanese Childhood MDS Study Group trial (MDS99). Pediatr Blood Cancer. 2009;53(6):1011-1015.
45. Marsh JC, Kulasekararaj AG. Management of the refractory aplastic anemia patient: what are the options? Blood. 2013;122(22):3561-3567.
46. Li X, Zhong H, Bao W, et al. Defective regulatory B-cell compartment in patients with immune thrombocytopenia. Blood. 2012;120(16):3318-3325.
47. Nishimoto T, Kuwana M. CD4+CD25+Foxp3+ regulatory T cells in the pathophysiology of immune thrombocytopenia. Semin Hematol. 2013;50(Suppl 1):S43-S49.
48. Tesse R, Del Vecchio GC, De Mattia D, Sangerardi M, Valente F, Giordano P. Association of interleukin-(IL)10 haplotypes and serum IL-10 levels in the progression of childhood immune thrombocytopenic purpura. Gene. 2012;505(1):53-56.
49. Zhao H, Zhang Y, Xiao G, Wu N, Xu J, Fang Z. Interleukin-18 gene promoter - 607 A/C polymorphism and the risk of immune thrombocytopenia. Autoimmunity. 2014;1-4.
50. Zhao H, Zhang Y, Xue F, Xu J, Fang Z. Interleukin-27 rs153109 polymorphism and the risk for immune thrombocytopenia. Autoimmunity. 2013;46(8):509-512.
51. Salzer E, Santos-Valente E, Klaver S, et al. B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ. Blood. 2013;121(16):3112-3116.
52. Wimmer K, Kratz CP, Vasen HF, et al; EU-Consortium Care for CMMRD (C4CMMRD). Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium 'care for CMMRD' (C4CMMRD). J Med Genet. 2014;51(6):355-365.
53. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA; American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-4207.
54. EWOG. European Working Group of MDS and JMML in Childhood; Director: C. Niemeyer; http://www.ewog-mds.org. Accessed August 2014.
55. ICIS. Imbach P, Kühne T. Intercontinental Cooperative ITP Study Group (ICIS - PARC-ITP)., CH-4031 Basel. Switzerland: University Children's Hospital UKBB, Hematology/Oncology; http://www.itpbasel.ch. Accessed August 2014.
56. CEREVANCE. Perel Y, Aladjidi N. CEREVANCE / cytopénies auto-immunes de l'enfant Bordeaux, France; http://www.chu-bordeaux.fr/Professionnel-de-sant%C3%A9/Les-maladies-rares/presentation/cerevance-cytopenies-auto-immunes-de-lenfant. Accessed August 2014.
57. Barzaghi F, Passerini L, Bacchetta R. Immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome: a paradigm of immunodeficiency with autoimmunity. Front Immunol. 2012;3:211.
58. Ochs HD, Ziegler SF, Torgerson TR. FOXP3 acts as a rheostat of the immune response. Immunol Rev. 2005;203:156-164.
59. Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010;10(7):490-500.
60. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4(4):330-336.
61. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299(5609):1057-1061.
62. 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(2):482-487.
63. Uzel G, Sampaio EP, Lawrence MG, et al. Dominant gain-of-function STAT1 mutations in FOXP3 wild-type immune dysregulation-polyendocrinopathy-enteropathy-X-linked-like syndrome. J Allergy Clin Immunol. 2013;131(6):1611-1623.
64. Kanai T, Jenks J, Nadeau KC. The STAT5b Pathway Defect and Autoimmunity. Front Immunol. 2012;3:234.
65. Barzaghi F, Passerini L, Gambineri E, et al. Demethylation analysis of the FOXP3 locus shows quantitative defects of regulatory T cells in IPEX-like syndrome. J Autoimmun. 2012;38(1):49-58.
66. De Martino L, Capalbo D, Improda N, et al. APECED: A Paradigm of Complex Interactions between Genetic Background and Susceptibility Factors. Front Immunol. 2013;4:331.
67. Janka GE, Lehmberg K. Hemophagocytic syndromes - an update. Blood Rev. 2014;28(4):135-142.
68. Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-131.
69. Huck K, Feyen O, Niehues T, et al. Girls homozygous for an IL-2-inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation. J Clin Invest. 2009;119(5):1350-1358.
70. Salzer E, Daschkey S, Choo S, et al. Combined immunodeficiency with life-threatening EBV-associated lymphoproliferative disorder in patients lacking functional CD27. Haematologica. 2013;98(3):473-478.
71. van Montfrans JM, Hoepelman AI, Otto S, et al. CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. J Allergy Clin Immunol. 2012;129(3):787-793, e6.
72. Bigley V, Collin M. Dendritic cell, monocyte, B and NK lymphoid deficiency defines the lost lineages of a new GATA-2 dependent myelodysplastic syndrome. Haematologica. 2011;96(8):1081-1083.
73. Dickinson RE, Griffin H, Bigley V, et al. Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Blood. 2011;118(10):2656-2658.
74. Dickinson RE, Milne P, Jardine L, et al. The evolution of cellular deficiency in GATA2 mutation. Blood. 2014;123(6):863-874.
75. Georgopoulos K, Moore DD, Derfler B. Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment. Science. 1992;258(5083):808-812.
76. Wang H, Ouyang H, Lai L, et al. Pathogenesis and regulation of cellular proliferation in acute lymphoblastic leukemia - the role of Ikaros. J BUON. 2014;19(1):22-28.
77. Goldman FD, Gurel Z, Al-Zubeidi D, et al. Congenital pancytopenia and absence of B lymphocytes in a neonate with a mutation in the Ikaros gene. Pediatr Blood Cancer. 2012;58(4):591-597.
78. John LB, Ward AC. The Ikaros gene family: transcriptional regulators of hematopoiesis and immunity. Mol Immunol. 2011;48(9-10):1272-1278.
79. Hernandez PA, Gorlin RJ, Lukens JN, et al. Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nat Genet. 2003;34(1):70-74.
80. Honda F, Kano H, Kanegane H, et al. The kinase Btk negatively regulates the production of reactive oxygen species and stimulation-induced apoptosis in human neutrophils. Nat Immunol. 2012;13(4):369-378.
81. Sills RH. Practical Algorithms in Pediatric Hematology and Oncology. Basel, Switzerland: Karger; 2003.
82. Brighton TA, Evans S, Castaldi PA, Chesterman CN, Chong BH. Prospective evaluation of the clinical usefulness of an antigen-specific assay (MAIPA) in idiopathic thrombocytopenic purpura and other immune thrombocytopenias. Blood. 1996;88(1):194-201.
83. Warner MN, Moore JC, Warkentin TE, Santos AV, Kelton JG. A prospective study of protein-specific assays used to investigate idiopathic thrombocytopenic purpura. Br J Haematol. 1999;104(3):442-447.
84. Raife TJ, Olson JD, Lentz SR. Platelet antibody testing in idiopathic thrombocytopenic purpura. Blood. 1997;89(3):1112-1114.
85. EBMT. European Society for Blood and Marrow Transplantation. www.ebmt.org Accessed August 2014.
86. Arnold DM. Positioning new treatments in the management of immune thrombocytopenia. Pediatr Blood Cancer. 2013;60(Suppl 1):S19-S22.
87. Basciano PA, Bussel JB. Thrombopoietin-receptor agonists. Curr Opin Hematol. 2012;19(5):392-398.
88. Wörmann B. Clinical indications for thrombopoietin and thrombopoietin-receptor agonists. Transfus Med Hemother. 2013;40(5):319-325.
89. Seidel MG, Urban C, Sipurzynski J, Beham-Schmid C, Lackner H, Benesch M. High response rate but short-term effect of romiplostim in paediatric refractory chronic immune thrombocytopenia. Br J Haematol. 2014;165(3):419-421.
90. Jordan SC, Reinsmoen N, Lai CH, Vo A. Novel immunotherapeutic approaches to improve rates and outcomes of transplantation in sensitized renal allograft recipients. Discov Med. 2012;13(70):235-245.
91. National Institutes of Health. ClinicalTrials.gov database. Available at: www.clinicaltrials.gov. Accessed August 2014.
92. Liu XG, Hou M. Immune thrombocytopenia and B-cell-activating factor/a proliferation-inducing ligand. Semin Hematol. 2013;50(Suppl 1):S89-S99.