Primary immunodeficiency genetic panel
Lymphadenopathy, splenomegaly, cytopenias, and lymphoma are common manifestations of both APDS and ALPS. Physicians of patients with probable but not definitive ALPS may consider referring to an immunologist for genetic testing, or ordering a primary immunodeficiency genetic testing panel.
De novo variants have also been observed, and while the prevalence has not been fully assessed, a large cohort suggests that around 20% of patients may have de novo variants. 2,13-16
However, APDS may be difficult to trace based on clinical history as symptoms can vary even within the same family.13
As there is a 50% of chance of APDS being passed from parent to child, family members of patients with APDS should also be genetically tested.
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PI is also referred to as an Inborn Error of Immunity (IEI).
1. Coulter TI, Chandra A, Bacon CM, et al. Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study. J Allergy Clin Immunol. 2017;139(2):597-606.e4. doi:10.1016/j.jaci.2016.06.021 2. Elkaim E, Neven B, Bruneau J, et al. Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: A cohort study. J Allergy Clin Immunol. 2016;138(1):210-218.e9. doi:10.1016/j.jaci.2016.03.022 3. Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N; members of the CEREDIH French PID study group. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunol. 2017;140(5):1388-1393.e8. doi:10.1016/j.jaci.2016.12.978 4. Hadjadj J, Aladjidi N, Fernandes H, et al. Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes. Blood. 2019;134(1):9-21. doi:10.1182/blood-2018-11-887141 5. Jamee M, Moniri S, Zaki-Dizaji M, et al. Clinical, Immunological, and Genetic Features in Patients with Activated PI3Kδ Syndrome (APDS): a Systematic Review. Clin Rev Allergy Immunol. 2020;59(3):323-333. doi:10.1007/s12016-019-08738-9 6. Mayor PC, Eng KH, Singel KL, et al. Cancer in primary immunodeficiency diseases: Cancer incidence in the United States Immune Deficiency Network Registry. J Allergy Clin Immunol. 2018;141(3):1028-1035. doi:10.1016/j.jaci.2017.05.024 7. Shapiro RS. Malignancies in the setting of primary immunodeficiency: Implications for hematologists/oncologists. Am J Hematol. 2011;86(1):48-55. doi:10.1002/ajh.21903 8. Rotz SJ, Ware RE, Kumar A. Diagnosis and management of chronic and refractory immune cytopenias in children, adolescents, and young adults [published correction appears in Pediatr Blood Cancer. 2019 Apr;66(4):e27581]. Pediatr Blood Cancer. 2018;65(10):e27260. doi:10.1002/pbc.27260 9. Sánchez-Ramón S, Bermúdez A, González-Granado LI, et al. Primary and Secondary Immunodeficiency Diseases in Oncohaematology: Warning Signs, Diagnosis, and Management. Front Immunol. 2019;10:586. Published 2019 Mar 26. doi:10.3389/fimmu.2019.00586 10. Kulm E, et al. Oral abstract presented at: 62nd Annual ASH Meeting; December 5-8, 2020. 11. Rao VK, Oliveira JB. How I treat autoimmune lymphoproliferative syndrome. Blood. 2011;118(22):5741-5751. doi:10.1182/blood-2011-07-325217 12. Chinn IK, et al. J Allergy Clin Immunol. 2020;145(1):46-69. 13. Lucas CL, Kuehn HS, Zhao F, et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency. Nat Immunol. 2014;15(1):88-97. doi:10.1038/ni.2771 14. Angulo I, Vadas O, Garçon F, et al. Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage. Science. 2013;342(6160):866-871. doi:10.1126/science.1243292 15. Lucas CL, Zhang Y, Venida A, et al. Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K. J Exp Med. 2014;211(13):2537-2547. doi:10.1084/jem.20141759 16. Deau MC, Heurtier L, Frange P, et al. A human immunodeficiency caused by mutations in the PIK3R1 gene [published correction appears in J Clin Invest. 2015 Apr;125(4):1764-5]. J Clin Invest. 2014;124(9):3923-3928. doi:10.1172/JCI75746