medigraphic.com
ISSN 1561-2996 (Electronic)
ISSN 0864-0289 (Print)

2021, Number 4

<< Back Next >>

Rev Cubana Hematol Inmunol Hemoter 2021; 37 (4)

Evans syndrome and immune dysregulation: molecular and etiopathogenic complexities

Soler NG, Escalona MLZ

Language: Spanish
References: 75
Page: 1-26
PDF size: 534.70 Kb.


ABSTRACT

Introduction: Evans syndrome is defined as the presence of autoimmune cytopenias affecting two or more blood cell lines, either simultaneously or sequentially. Most often, this refers to the combination of autoimmune hemolytic anemia and immune thrombocytopenia but can include autoimmune neutropenia as well. The etiology of Evans syndrome has been attributed to pathologic autoantibody production against the blood cells, but the true underlying cause remaining unknown.
Objective: to explain the relationship of Evans syndrome with dysregulation of the immune system.
Method: a review of the literature in English and Spanish was carried out through the PubMed website and the academic Google search engine for articles published on the subject. 69,73 % corresponded to the last 5 years.
Conclusions: the immunopathology of Evans syndrome can be attributed to an alteration in the development or function of lymphocytes, such that the immune balance is inclined towards self-reactivity.


REFERENCES

  1. Al Ghaithi I, Wright NAM, Breakey VR, Cox K, Warias A, Wong T, et al. Combined autoimmune cytopenias presenting in childhood. Pediatr Blood Cancer. 2016;63:292-8. DOI: https://:10.1002/pbc.25769

  2. Mantadakis E, Farmaki E. Natural history, pathogenesis, and treatment of Evans syndrome in children. J Pediatr Hematol Oncol. 2017;39:413-9. DOI: https://:10.1097/MPH.0000000000000897

  3. Michel M, Chanet V, Dechartres A, Morin AS, Piette JC, Cirasino L, et al. The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases. Blood. 2009;114(15):3167-72. DOI: https://:10.1182/blood-2009-04-215368

  4. Sipurzynski J, Fahrner B, Kerbl R, Crazzolara R, Jones N, Ebetsberger G, et al. Management of chronic immune thrombocytopenia in children and adolescents: lessons from an Austrian national cross-sectional study of 81 patients. Semin Hematol. 2016;53:S43-S47. DOI: https://:10.1053/j.seminhematol.2016.04.013

  5. Yong M, Schoonen WM, Li L, Kanas G, Coalson J, Mowat F, et al. Epidemiology of paediatric immune thrombocytopenia in the General Practice Research Database. Br J Haematol. 2010;149(6):855-64. DOI: https://:10.1111/j.1365-2141.2010.08176.x

  6. Aladjidi N, Jutand MA, Beaubois C, Fernandes H, Jeanpetit J, Coureau G, et al. Reliable assessment of the incidence of childhood autoimmune hemolytic anemia. Pediatr Blood Cancer. 2017;64:e26683. DOI: https://:10.1002/pbc.26683

  7. Olmsted T, Despotovic JM. Primary and Secondary Immune Cytopenias: Evaluation and Treatment Approach in Children. Hematol Oncol Clin N Am. 2019;33:489-506. DOI: https://10.1016/j.hoc.2019.01.005

  8. Hadjadj J, Aladjidi N, Fernandes H, Leverger G, Magerus-Chatinet A, Mazerolles F, et al. Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes. Blood. 2019;134(1):9-21. DOI: https://10.1182/blood-2018-11-887141

  9. Sipurzynski J, Fahrner B, Kerbl R, Crazzolara R, Jones N, Ebetsberger G, et al. Management of chronic immune thrombocytopenia in children and adolescents: lessons from an Austrian national cross-sectional study of 81 patients. Semin Hematol. 2016;53(S1):S43-7. DOI: https://:10.1053/j.seminhematol.2016.04.013

  10. Norton A, Roberts I. Management of Evans syndrome. B J Haematol. 2006;132: 125-137. DOI: https://:10.1111/j.1365-2141.2005.05809.x

  11. Aladjidi N, Leverger G, Leblanc T, Quitterie Picat M, Michel G, Bertrand Y, et al. New insights into childhood autoimmune hemolytic anemia: a French national observational study of 265 children. Haematologica. 2011;96(5):655-63. DOI: https://:10.3324/haematol.2010.036053

  12. Bride K, Teachey D. Autoimmune lymphoproliferative syndrome: more than a FAScinating disease. F1000Res. 2017;6:1928.DOI: https://:10.12688/f1000research.11545.1

  13. Schmidt RE, Grimbacher B, Witte T. Autoimmunity and primary immunodeficiency: two sides of the same coin? Nat Rev Rheumatol. 2018;14(1):7-18. DOI: https://:10.1038/nrrheum.2017.198

  14. Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, et al. The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity. J Allergy Clin Immunol Pract. 2019;7(6):17631-70. DOI: https://:10.1016/j.jaip.2019.02.004

  15. NijmanI J, van Montfrans JM, Hoogstraat M, Boes ML, van de Corput L, Renner ED, et al. Targeted next-generation sequencing: a novel diagnostic tool for primary immunodeficiencies. J Allergy Clin Immunol. 2014;133(2):529-34. DOI: https://:10.1016/j.jaci.2013.08.032

  16. Li E, Grimes AB, Rider NL, Mahoney DH, Fleisher TA, Shearer WT. Diagnostic dilemma: ALPS versus Evans syndrome. Clin Immunol. 2017;183:247-8. DOI: https://:10.1016/j.clim.2017.08.006

  17. Zhang L, Wu X, Wang L, Li J, Chen H, Zhao Y, et al. Clinical features of systemic lupus erythematosus patients complicated with Evans syndrome: a case-control, single center study. Medicine (Baltimore). 2016;95(15):e3279. DOI: https://:10.1097/MD.0000000000003279

  18. Patel B P, Jakob J. A Rare Case of Simultaneous Evans Syndrome and Primary Antiphospholipid Syndrome. Cureus. 2020;12(2): e6845. DOI: https://:10.7759/cureus.6845

  19. Matson DR, Yang DT. Autoimmune Lymphoproliferative Syndrome: An Overview. Arch Pathol Lab Med. 2020;144:245-51; DOI: https://:10.5858/arpa.2018-0190-RS

  20. Xie Y, Pittaluga S, Price S, Raffeld M, Hahn J, Jaffe ES, et al. Bone marrow findings in autoimmune lymphoproliferative syndrome with germline FAS mutation. Haematologica. 2017;102(2):364-72. DOI: https://:10.3324/haematol.2015.138081

  21. Seif AE, Manno CS, Sheen C, Grupp SA, Teachey DT. Identifying autoimmune lymphoproliferative syndrome in children with Evans syndrome: a multi-institutional study. Blood. 2010;115(11):2142-5. DOI: https://:10.1182/blood-2009-08-239525

  22. Oliveira JB, Bleesing JJ, Dianzani U, Fleisher TA, Jaffe ES, Lenardo MJ, et al. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop. Blood. 2010;116(14):e35-40. DOI: https://:10.1182/blood-2010-04-280347

  23. Ho HE, Cunningham-Rundles C. Non-infectious Complications of Common Variable Immunodeficiency: Updated Clinical Spectrum, Sequelae, and Insights to Pathogenesis. Front Immunol. 2020;11:149. DOI: https://:10.3389/fimmu.2020.00149

  24. Feuille EJ, Anooshiravani N, Sullivan KE, Fuleihan RL, Cunningham-Rundles C. Autoimmune cytopenias and associated conditions in CVID: a report from the USIDNET Registry. J Clin Immunol. 2017;38(1):28-34. DOI: https://:10.1007/s10875-017-0456-9.

  25. Lube GE, Ferriani MP, Campos LM, Terreri MT, Bonfá E, Saad C, et al. Evans syndrome at childhood-onset systemic lupus erythematosus diagnosis: a large multicenter study. Pediatr Blood Cancer. 2016;63(7):1238-43. DOI: https://:10.1002/pbc.25976

  26. Burnett DL, Langley DB, Schofield P, Hermes JR, Chan TD, Jackson J, et al. Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination. Science. 2018;360(6385):223-6. DOI: https://:10.1126/science.aao3859

  27. Warnatz K, Wehr C, Dräger R, Schmidt S, Eibel H, Schlesier M, et al. Expansion of CD19(hi)CD21(lo/neg) B cells in common variable immunodeficiency (CVID) patients with autoimmune cytopenia. Immunobiology. 2002;206(5):502-13. DOI: https://:10.1078/0171-2985-00198

  28. Romberg N, Le Coz C, Glauzy S, Schickel JN, TrofaBA M, Nolan BE, et al. Patients with common variable immunodeficiency with autoimmune cytopenias exhibit hyperplastic yet inefficient germinal center responses. J Allergy Clin Immunol. 2019;143:258 e265. DOI: https://:10.1016/j.jaci.2018.06.012

  29. Kuwana M, Okazaki Y, Kajihara M, Kaburaki J, Miyazaki H, Kawakami Y, et al. Autoantibody to c-Mpl (thrombopoietin receptor) in systemic lupus erythematosus: relationship to thrombocytopenia with megakaryocytic hypoplasia. Arthritis Rheum. 2002;46:2148-59. DOI: https://:10.1002/art.10420

  30. Cines DB, Liebman H, Stasi R. Pathobiology of secondary immune thrombocytopenia. Semin Hematol. 2009;46(1Suppl2):S2-14. DOI: https://:10.1053/j.seminhematol.2008.12.005

  31. Nakamura M, Tanaka Y, Satoh T, Kawai M, Hirakata M, Kaburaki J, et al. Autoantibody to CD40 ligand in systemic lupus erythematosus: association with thrombocytopenia but not thromboembolism. Rheumatology (Oxford). 2006;45(2):150-6. DOI: https://:10.1093/rheumatology/kei118

  32. Liu Y, Chen S, Sun Y, Lin Q, Liao X, Zhang J, et al. Clinical characteristics of immune thrombocytopenia associated with autoimmune disease: a retrospective study. Medicine (Baltimore). 2016;95(50):e5565. DOI: https://:10.1097/MD.0000000000005565

  33. Molnár E, Radwan N, Kovács G, Andrikovics H, Henriquez F, Zarafov A, et al. Key diagnostic markers for Autoimmune Lymphoproliferative Syndrome with molecular genetic diagnosis. Blood blood.2020005486. DOI: https://:10.1182/blood.2020005486

  34. Takagi M, Hoshino A, Yoshida K, Ueno H, Imai K, Piao J, et al. Genetic heterogeneity of uncharacterized childhood autoimmune diseases with lymphoproliferation. Pediatr Blood Cancer. 2018; 65:e26831. DOI: https://:10.1002/pbc.26831

  35. Li P, Huang P, Yang Y, Hao M, Peng H, Li F. Updated Understanding of Autoimmune Lymphoproliferative Syndrome (ALPS). Clinic Rev Allerg Immunol. DOI: https://:10.1007/s12016-015-8466-y

  36. Kuehn HS, Caminha I, Niemela JE, Rao VK, Davis J, Fleisher TA, et al. FAS haploinsuficiency is a common disease mechanism in the human autoimmune lymphoproliferative syndrome. J Immunol. 2011;186(10):6035-43. DOI: https://:10.4049/jimmunol.1100021

  37. Magerus-Chatinet A, Neven B, Stolzenberg MC, Daussy C, Arkwright PD, Lanzarotti N, et al. Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation. J Clin Invest. 2011;121(1):106-12. DOI: https://: 10.1172/JCI43752

  38. Boggio E, Gigliotti CL, Rossi D, Toffoletti E, Cappellano G, Clemente N, et al. Decreased function of Fas and variations of the perforin gene in adult patients with primary immune thrombocytopenia. B J Haematol. 2017;176:258-67. DOI: https://: 10.1111/bjh.14248

  39. van Schouwenburg PA, IJspeert H, Pico-Knijnenburg I, Dalm VASH, van Hagen PM, van Zessen D, et al. Identification of CVID Patients With Defects in Immune Repertoire Formation or Specification. Front Immunol. 2018;9:2545. DOI: https://: 10.3389/fimmu.2018.02545

  40. Odnoletkova I, Kindle G, Quinti I, Grimbacher B, Knerr V, Gathmann B, et al. The burden of common variable immunodeficiency disorders: a retrospective analysis of the European Society for Immunodeficiency (ESID) registry data. Orphanet J Rare Dis. 2018;13(1):201. DOI: https://:10.1186/s13023-018-0941-0

  41. Yazdani R, Seify R, Ganjalikhani-Hakemi M, Abolhassani H, Eskandari N, Golsaz-Shirazi F, et al. Comparison of various classifications for patients with common variable immunodeficiency (CVID) using measurement of B-cell subsets. Allergol Immunopathol (Madr). 2017;45(2):183-92. DOI: https://:10.1016/j.aller.2016.07.001

  42. Meffre E. The establishment of early B cell tolerance in humans: lessons from primary immunodeiciency diseases. Ann N Y Acad Sci. 2011;1246:1-10. DOI: https://:10.1111/j.1749-6632.2011.06347.x

  43. Yazdani R, Habibi S, Sharifi L, Azizi G, Abolhassani H, Olbrich P, et al. Common variable immunodeficiency: epidemiology, pathogenesis, clinical manifestations, diagnosis, classification and management. J Investig Allergol Clin Immunol. 2020;30(1):14-34. DOI: https://:10.18176/jiaci.0388.

  44. Takagi M, Ogata S, Ueno H, Yoshida L, Yeh T, Hoshino A, et al. Haploinsufficiency of TNFAIP3 (A20) by germline mutation is involved in autoimmune lymphoproliferative syndrome. J Allergy Clin I mmunol. 2017;139(6):1914-22. DOI: https://:10.1016/j.jaci.2016.09.038

  45. Yakaboski E, Fuleihan RL, Sullivan KE, Cunningham-Rundles C, Feuille E. Lymphoproliferative Disease in CVID: A Report of Types and Frequencies from a US Patient Registry. J Clin Immunol. 2020;40(3):524-30. DOI: https://:10.1007/s10875-020-00769-8.

  46. Oliveira JB, Bidère N, Niemela JE, Zheng L, Sakai K, Nix CP, et al. NRAS mutation causes a human autoimmune lymphoproliferative syndrome. Proc Natl Acad Sci U S A. 2007;104(21):8953-8. DOI: https://:10.1073/pnas.0702975104.

  47. Niemela J, Lu L, Fleisher TA, Davis J, Caminha I, Natter M, et al. Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. Blood. 2011;117:2883-6. DOI: https://:10.1182/blood-2010-07-295501.

  48. Chun HJ, Zheng I, Ahmad M, Wang J, Speirs CK, Siegel RM, et al. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeiciency. Nature. 2002;419(6905):395-9. DOI: https://:10.1038/nature01063.

  49. Shiota M, Yang X, Kubokawa M, Morishima T, Tanaka K, Mikami M, et al. Somatic mosaicism for a NRAS mutation associates with disparate clinical features in RAS-associated leukoproliferative disease: a report of two cases. J Clin Immunol. 2015;35(5):454-8. DOI: https://:10.1007/s10875-015-0163-3

  50. Niemela J, Lu L, Fleisher TA, Davis J, Caminha I, Natter M, et al. Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. Blood. 2011;117:2883-6. DOI: https://:10.1182/blood-2010-07-295501

  51. Kucuk ZY, Charbonnier LM, McMasters RL, Chatila T, Bleesing JJ. CTLA-4 haploinsuficiency in a patient with an autoimmune lymphoproliferative disorder. J Allergy Clin Immunol. 2017;140(3):862-4. DOI: https://:10.1016/j.jaci.2017.02.032

  52. Gámez-Díaz L, August D, Stepensky P, Revel-Vilk S, Seidel MG, Noriko M, et al. The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency. J Allergy Clin Immunol. 2016;137(1):223-30. DOI: https://: 10.1016/j.jaci.2015.09.025.

  53. Kostel Bal S, Haskologlu S, Serwas NK, Islamoglu C, Aytekin C, Kendirli T, et al. Multiple presentations of LRBA deficiency: a single-center experience. J Clin Immunol. 2017;37(8):790-800. DOI: https://:10.1007/s10875-017-0446-y.

  54. Coulter TI, Chandra A, Bacon CM, Babar J, Curtis J, Screaton N, et al. Clinical spectrum and features of activated phosphoinositide 3-kinase d syndrome: a large patient cohort study. J Allergy Clin Immunol. 2017;139(2):597-606. DOI: https://: 10.1016/j.jaci.2016.06.021.

  55. Consonni F, Dotta L, Todaro F, Vairo D, Badolato R. Signal transducer and activator of transcription gain-of-function primary immunodeficiency/immunodysregulation disorders. Curr Opin Pediatr. 2017;29(6):711-7. DOI: https://: 10.1097/MOP.0000000000000551.

  56. Schwab C, Gabrysch A, Olbrich P, Patiño V, Warnatz K, Wolff D, et al. Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects. J Allergy Clin Immunol. 2018;142(6):1932-46. DOI: https://: 10.1016/j.jaci.2018.02.055.

  57. Lo B, Fritz JM, Su HC, Uzel G, Jordan MB, Lenardo MJ. CHAI and LATAIE: new genetic diseases of CTLA-4 checkpoint insufficiency. Blood. 2016;128:1037-42. DOI: https://10.1182/blood-2016-04-712612 .

  58. Lévy E, Stolzenberg MC, Bruneau J, Breton S, Neven B, Sauvion S, et al. LRBA deficiency with autoimmunity and early onset chronic erosive polyarthritis. Clin Immunol. 2016;168:88-93. DOI: https://:10.1016/j.clim.2016.03.006.

  59. Azizi G, Abolhassani H, Zaki-Dizaji M, Habibi S, Mohammadi H, Shaghaghi M, et al. Polyautoimmunity in patients with LPS-responsive beige-like anchor (LRBA) deficiency. Immunol Investig. 2018;47(5):457-67. DOI: https://: 10.1080/08820139.2018.1446978.

  60. Besnard C, Levy E, Aladjidi N, Stolzenberg MC, Magerus-Chatinet A, Alibeu O, et al. Pediatric-onset Evans syndrome: Heterogeneous presentation and high frequency of monogenic disorders including LRBA and CTLA4 mutations. Clin Immunol. 2018;188:52-57. DOI: https://:10.1016/j.clim.2017.12.009

  61. Coulter TI, Chandra A, Bacon CM, Babar J, Curtis J, Screaton N, et al. Clinical spectrum and features of activated phosphoinositide 3-kinase d syndrome: a large patient cohort study. J Allergy Clin Immunol. 2017;139(2):597-606.e4. DOI: https://: 10.1016/j.jaci.2016.06.021.

  62. Volkl S, Rensing-Ehl A, Allgauer A, Schreiner E, Lorenz MR, Rohr J, et al. Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome. Blood. 2016;128(2):227-38. DOI: https://:10.1182/blood-2015-11-685024.

  63. Preite S, Gomez-Rodriguez J, Cannons JL, Schwartzberg PL. T and B-cell signaling in activated PI3K delta syndrome: From immunodeficiency to autoimmunity. Immunol Rev. 2019;291(1):154-73. DOI: https://:10.1111/imr.12790.

  64. Klemann C, Esquivel M, Magerus-Chatinet A, Lorenz MR, Fuchs I, Neveux N, et al. Evolution of disease activity and biomarkers on and off rapamycin in 28 patients with autoimmune lymphoproliferative syndrome. Haematologica. 2017;102(2):e52-e56. DOI: https://:10.3324/haematol.2016.153411.

  65. Thauland TJ, Pellerin L, Ohgami RS, Bacchetta R, Butte MJ. Case Study: Mechanism for Increased Follicular Helper T Cell Development in Activated PI3K Delta Syndrome. Front Immunol. 2019;10:753. DOI: https://10.3389/fimmu.2019.00753.

  66. Coulter TI, Chandra A, Bacon CM, Babar J, Curtis J, Screaton N, et al. Clinical spectrum and features of activated phosphoinositide 3-kinase d syndrome: a large patient cohort study. J Allergy Clin Immunol. 2017;139(2):597-606. DOI: https://10.1016/j.jaci.2016.06.021.

  67. Consonni F, Dotta L, Todaro F, Vairo D, Badolato R. Signal transducer and activator of transcription gain-of-function primary immunodeficiency/immunodysregulation disorders. Curr Opin Pediatr. 2017;29(6):711-7. DOI: https://10.1097/MOP.0000000000000551.

  68. Weinacht KG, Charbonnier LM, Alrogi F, Plant A, Qiao Q, Wu H, et al. Ruxolitinib reverses dysregulated T helper cell responses and controls autoimmunity caused by a novel signal transducer and activator of transcription 1 (STAT1) gain-of-function mutation. J Allergy Clin Immunol. 2017;139(5):1629-40. DOI: https://10.1016/j.jaci.2016.11.022.

  69. Forbes LR, Milner J, Haddad E. Signal transducer and activator of transcription 3: a year in review. Curr Opin Hematol. 2016;23(1):23-7. DOI: https://10.1097/MOH.0000000000000206.

  70. Nabhani S, Schipp C, Miskin H, Levin C, Postovsky S, Dujovny T, et al. STAT3 gain-of-function mutations associated with autoimmune lymphoproliferative syndrome like disease deregulate lymphocyte apoptosis and can be targeted by BH3 mimetic compounds. Clin Immunol. 2017;181:32-42. DOI: https://10.1016/j.clim.2017.05.021.

  71. Schafiq N, Schipp C, Miskin H, Levin C, Postovsky S, Dujovny T, et al. STAT3 gain-of-function mutations associated with autoimmune lymphoproliferative syndrome like disease deregulate lymphocyte apoptosis and can be targeted by BH3 mimetic compounds. Clin Immunol. 2017; 181:32-42. DOI: https://10.1016/j.clim.2017.05.021

  72. Yakaboski E, Fuleihan RL, Sullivan KE, Cunningham-Rundles C, Feuille E. Lymphoproliferative Disease in CVID: A Report of Types and Frequencies from a US Patient Registry. J Clin Immunol. 2020; 40(3):524-30. DOI: https://10.1007/s10875-020-00769-8.

  73. Bleesing JJ, Brown MR, Straus SE, Dale JK, Siegel RM, Johnson M, et al. Immunophenotypic profiles in families with autoimmune lymphoproliferative syndrome. Blood. 2001;98(8):2466-73. DOI: https://10.1182/blood.v98.8.2466.

  74. Caminha I, Fleisher TA, Hornung RL, Dale JK, Niemela JE, Price S, et al. Using biomarkers to predict the presence of FAS mutations in patients with features of the autoimmune lymphoproliferative syndrome. J Allergy Clin Immunol. 2010;125(4):946-9. DOI: https://10.1016/j.jaci.2009.12.983.

  75. Maglione PJ. Autoimmune and lymphoproliferative complications of common variable immunodeiciency. Curr Allergy Asthma Rep. 2016;16(3):19. DOI: https://10.1007/s11882-016-0597-6




2020     |     www.medigraphic.com