Autoimmune lymphoproliferative syndrome is a rare genetic disorder characterized by dysregulation of the immune system due to defective Fas mediated lymphocyte apoptosis. The clinical spectrum includes lymphoproliferative disease with lymphadenopathy, hepatomegaly, splenomegaly and an increased risk of lymphoma, as well as autoimmune disease typically involving blood cells. Definitive diagnosis is made by demonstrating infectious/non-malignant chronic lymphoproliferation for more than six months, high CD3+CD4−CD8− T Cell and defective lymphocyte apoptosis or one of the FAS, FASL, CASP10 mutations. Since clinical and laboratory findings may overlap with other immune dysregulation or autoimmune diseases, differential diagnosis of autoimmune lymphoproliferative syndrome remains essential. Here, we present three cases of suspected autoimmune lymphoproliferative syndrome with clinical and laboratory findings, which resulted in three different diagnoses (chronic idiopathic thrombocytopenic purpura, ALPS-like and ALPS) after diagnostic evaluations. For all three cases, next-generation sequencing, flow cytometric analysis, protein expression and Fas mediated lymphocyte apoptosis with functional assays were performed.
Citation: Tuba Karakurt, Nurhan Kasap, Kübra Aslan, Hayrunnisa Bekis Bozkurt, Fatma Bal Cetinkaya, Gizem Uslu, Zafer Bicakci, Filiz Özen, Özlem Cavkaytar, Ahmet Eken, Mustafa Arga. Suspected ALPS with clinical and laboratory findings: Three patients—three different diagnoses[J]. AIMS Allergy and Immunology, 2023, 7(4): 304-312. doi: 10.3934/Allergy.2023020
Autoimmune lymphoproliferative syndrome is a rare genetic disorder characterized by dysregulation of the immune system due to defective Fas mediated lymphocyte apoptosis. The clinical spectrum includes lymphoproliferative disease with lymphadenopathy, hepatomegaly, splenomegaly and an increased risk of lymphoma, as well as autoimmune disease typically involving blood cells. Definitive diagnosis is made by demonstrating infectious/non-malignant chronic lymphoproliferation for more than six months, high CD3+CD4−CD8− T Cell and defective lymphocyte apoptosis or one of the FAS, FASL, CASP10 mutations. Since clinical and laboratory findings may overlap with other immune dysregulation or autoimmune diseases, differential diagnosis of autoimmune lymphoproliferative syndrome remains essential. Here, we present three cases of suspected autoimmune lymphoproliferative syndrome with clinical and laboratory findings, which resulted in three different diagnoses (chronic idiopathic thrombocytopenic purpura, ALPS-like and ALPS) after diagnostic evaluations. For all three cases, next-generation sequencing, flow cytometric analysis, protein expression and Fas mediated lymphocyte apoptosis with functional assays were performed.
splenomegaly
hepatomegaly
lymphadenopathy
primary immunodeficiencies
autoimmune lymphoproliferative syndrome
CD4−CD8− double-negative T
| [1] | Riaz I bin, Faridi W, Patnaik MM, et al. (2019) A systematic review on predisposition to lymphoid (B and T cell) neoplasias in patients with primary immunodeficiencies and immune dysregulatory disorders (inborn errors of immunity). Front Immunol 10: 777. https://doi.org/10.3389/fimmu.2019.00777 |
| [2] | Matson DR, Yang DT (2020) Autoimmune lymphoproliferative syndrome: An overview. Arch Pathol Lab Med 144: 245-251. https://doi.org/10.5858/arpa.2018-0190-RS |
| [3] | Hafezi N, Zaki-Dizaji M, Nirouei M, et al. (2021) Clinical, immunological, and genetic features in 780 patients with autoimmune lymphoproliferative syndrome (ALPS) and ALPS-like diseases: A systematic review. Pediatr Allergy Immunol 32: 1519-1532. https://doi.org/10.1111/pai.13535 |
| [4] | López-Nevado M, González-Granado LI, Ruiz-García R, et al. (2021) Primary immune regulatory disorders with an autoimmune lymphoproliferative syndrome-like phenotype: immunologic evaluation, early diagnosis and management. Front Immunol 12: 671755. https://doi.org/10.3389/fimmu.2021.671755 |
| [5] | Casamayor-Polo L, López-Nevado M, Paz-Artal E, et al. (2021) Immunologic evaluation and genetic defects of apoptosis in patients with autoimmune lymphoproliferative syndrome (ALPS). Crit Rev Clin Lab Sci 58: 253-274. https://doi.org/10.1080/10408363.2020.1855623 |
| [6] | Oliveira JB, Bleesing JJ, Dianzani U, et al. (2010) Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop. Blood 116: e35-e40. https://doi.org/10.1182/blood-2010-04-280347 |
| [7] | Seidel MG, Kindle G, Gathmann B, et al. (2019) The European Society for Immunodeficiencies (ESID) registry working definitions for the clinical diagnosis of inborn errors of immunity. J Allergy Clin Immunol Pract 7: 1763-1770. https://doi.org/10.1016/j.jaip.2019.02.004 |
| [8] | Neven B, Magerus-Chatinet A, Florkin B, et al. (2011) A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation. Blood 118: 4798-4807. https://doi.org/10.1182/blood-2011-04-347641 |
| [9] | Molnár E, Radwan N, Kovács G, et al. (2020) Key diagnostic markers for autoimmune lymphoproliferative syndrome with molecular genetic diagnosis. Blood 136: 1933-1945. https://doi.org/10.1182/blood.2020005486 |
| [10] | Caminha I, Fleisher TA, Hornung RL, et al. (2010) Using biomarkers to predict the presence of FAS mutations in patients with features of the autoimmune lymphoproliferative syndrome. J Allergy Clin Immunol 125: 946-949. https://doi.org/10.1016/j.jaci.2009.12.983 |
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Tuba Karakurt, Nurhan Kasap, Kübra Aslan, Hayrunnisa Bekis Bozkurt, Fatma Bal Cetinkaya, Gizem Uslu, Zafer Bicakci, Filiz Özen, Özlem Cavkaytar, Ahmet Eken, Mustafa Arga. Suspected ALPS with clinical and laboratory findings: Three patients—three different diagnoses[J]. AIMS Allergy and Immunology, 2023, 7(4): 304-312. doi: 10.3934/Allergy.2023020
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