Clinical, immunological, and genetic features in 780 patients with autoimmune lymphoproliferative syndrome (ALPS) and ALPS‐like diseases: A systematic review

Abstract

AbstractBackgroundAutoimmune 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.MethodsThe 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.ResultsTotally, 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.ConclusionOur 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.