Review Article

Monogenic Disorder Associated with Autoimmune Lymphoproliferative Syndrome-Like Phenotype: A Systematic Review


Background: Autoimmune lymphoproliferative syndrome (ALPS) is a congenital disorder that results in an apoptosis impairment of lymphocytes, leading to chronic lymphoproliferation and autoimmunity, mainly autoimmune cytopenia. Some of autoreactive T cells cannot become apoptosis in activation-induced cell death (AICD) pathway; therefore, they have accumulation of autoreactive TCRαβ+CD4−CD8− doublenegative T (αβ- DNT) cells, leading to cytopenia, splenomegaly, lymphadenopathy, autoimmune disorders and a greatly increased lifetime risk of lymphoma. FAS, FASL, CASP8 and CASP10 gene defects are often responsible for the disease, the phenotype of which can vary from asymptomatic/mild forms to severe disease. More rarely, defects are associated to other genes involved in ALPS-like phenotype.
Methods: A systematic literature search was performed in Web of Science, PubMed and Scopus from the earliest available date to march 2021 with standard keywords to find patients with ALPS-like phenotypes. Demographic, clinical, immunological and molecular data were extracted.
Results: In this systematic review we reported 61 patients with genetically determined ALPS-like. Most of ALPS-like cases carry mutations in the STAT3 (n=15), LRBA (n=11) and CARD11 (n=8) genes. The most common presentation was splenomegaly and lymphadenopathy followed by hepatomegaly. The most common autoimmunity was autoimmune hemolytic anemia and immune thrombocytopenic purpura followed by autoimmune neutropenia. Elevated serum immunoglobulin was reported especially in IgG, IgM and IgA.
Conclusion: In the present study, 61 patients with genetically determined ALPS-like were examined. Our results showed that most of ALPS-like cases carry mutations in the STAT3. We reported that the most common presentations were splenomegaly and lymphadenopathy. Elevated serum immunoglobulin, IL-10, vitamin B12 and increased proportion of DNT cells were reported.

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IssueVol 4, No 2 (2021) QRcode
SectionReview Article
Primary Immunodeficiency ALPS Autoimmune Lymphoproliferative Like Syndrome Lymphoproliferation Autoimmunity LRBA STAT3

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How to Cite
Nirouei M, Hafezi N, Rasouli SE. Monogenic Disorder Associated with Autoimmune Lymphoproliferative Syndrome-Like Phenotype: A Systematic Review. Immunol Genet J. 2021;4(2):76-86.