Clinical, Immunological, and Genetic Features in 780 Patients With Autoimmune Lymphoproliferative Syndrome (Alps) and Alps-Like Diseases: A Systematic Review Publisher Pubmed



Hafezi N¹ ; Zakidizaji M² ; Nirouei M^{3, 4} ; Asadi G⁵ ; Sharifinejad N^{3, 4} ; Jamee M^{6, 7} ; Erfan Rasouli S^{3, 4} ; Hamedifar H^{8, 9} ; Sabzevari A^{8, 10} ; Chavoshzadeh Z^{6, 11} ; Yazdani R¹² ; Abolhassani H¹³ ; Aghamohammadi A¹² ; Azizi G^{7, 12} Show Affiliations
Source: Pediatric Allergy and Immunology Published:2021

Abstract

Background: Autoimmune lymphoproliferative syndrome (ALPS) is a group of genetic disorders characterized by early-onset lymphoproliferation, autoimmune cytopenias, and susceptibility to lymphoma. The majority of ALPS patients carry heterozygous germline mutations in the TNFRSF6 gene. In this study, we conducted a systematic review of patients with ALPS and ALPS-like syndrome. Methods: The literature search was performed in Web of Science, Scopus, and PubMed databases to find eligible studies. Additionally, the reference list of all included papers was hand-searched for additional studies. Demographic, clinical, immunological, and molecular data were extracted and compared between the ALPS and ALPS-like syndrome. Results: Totally, 720 patients with ALPS (532 genetically determined and 189 genetically undetermined ALPS) and 59 cases with ALPS-like phenotype due to mutations in genes other than ALPS genes were assessed. In both ALPS and ALPS-like patients, splenomegaly was the most common clinical presentation followed by autoimmune cytopenias and lymphadenopathy. Among other clinical manifestations, respiratory tract infections were significantly higher in ALPS-like patients than ALPS. The immunological analysis showed a lower serum level of IgA, IgG, and lymphocyte count in ALPS-like patients compared to ALPS. Most (85%) of the ALPS and ALPS-like cases with determined genetic defects carry mutations in the FAS gene. About one-third of patients received immunosuppressive therapy with conventional or targeted immunotherapy agents. A small fraction of patients (3.3%) received hematopoietic stem cell transplantation with successful engraftment, and all except two patients survived after transplantation. Conclusion: Our results showed that the FAS gene with 85% frequency is the main etiological cause of genetically diagnosed patients with ALPS phenotype; therefore, the genetic defect of the majority of suspected ALPS patients could be confirmed by mutation analysis of FAS gene. © 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.