Magerus A, Rensing-Ehl A, Rao VK, Teachey DT, Rieux-Laucat F, Ehl S. Autoimmune lymphoproliferative immunodeficiencies (ALPIDs): A proposed approach to redefining ALPS and other lymphoproliferative immune disorders. J Allergy Clin Immunol. 2024 Jan;153(1):67-76. doi: 10.1016/j.jaci.2023.11.004. Epub 2023 Nov 17. PMID: 37977527; PMCID: PMC10841637.
Publication Citation
Abstract
Chronic nonmalignant lymphoproliferation and autoimmune cytopenia are relevant manifestations of immunohematological diseases of childhood. Their diagnostic classification is challenging, but important for therapy. Autoimmune-lymphoproliferative syndrome (ALPS) is a genetically defined inborn error of immunity combining these manifestations, but can only explain a small proportion of cases. Diagnostic categories such as „ALPS-like“ disease, common variable immunodeficiency (CVID), or Evans syndrome have therefore been used. Advances in genetics and increasing availablity of targeted therapies call for more therapy-oriented disease classification. Moreover, recent discoveries in the (re-) analysis of genetic conditions affecting FAS signaling ask for a more precise definition of ALPS. In this review, we propose the term autoimmune-lymphoproliferative immunodeficiencies (ALPID) for a disease phenotype that is enriched for patients with genetic diseases for which targeted therapies are available. For patients without a current molecular diagnosis it defines a subgroup of immune dysregulatory disorders for further studies. Within the concept of ALPID, we propose a revision of the ALPS classification, restricting the use of this term to conditions with clear evidence of perturbation of FAS signaling and resulting specific biological and clinical consequences. This proposed approach to redefining ALPS and other lymphoproliferative conditions provides a framework for disease classification and diagnosis relevant for the many specialists confronted with these diseases.