{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T08:23:11Z","timestamp":1769329391316,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytometry Part B Clinical"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>X\u2010linked inhibitor of apoptosis (XIAP) deficiency is an infrequent inborn error of immunity caused by mutations in XIAP gene. Most cases present with absence of XIAP protein which can be detected by flow cytometry (FC), representing a rapid diagnostic method. However, since some genetic defects may not preclude protein expression, it is important to include a complementary functional test in the laboratory workup of these patients. L\u2010selectin (CD62\u2010L) is a molecule that is cleaved from the surface membrane of leukocytes upon stimulation of different receptors such as toll like receptors (TLRs) and nucleotide\u2010binding oligomerization domain\u2010like receptors (NLRs), including NOD2. Considering that XIAP deficiency impairs NOD2 signaling, we decided to assess CD62\u2010L down\u2010regulation by FC post\u2010stimulation of neutrophils and monocytes with L18\u2010muramyl Di\u2010Peptide (L18\u2010MDP), a NOD2 specific agonist, in order to develop a novel assay for the functional evaluation of patients with suspicion of XIAP defects. Whole blood samples from 20 healthy controls (HC) and four patients with confirmed molecular diagnosis of XIAP deficiency were stimulated with 200\u2009ng\/mL of L18\u2010MDP for 2\u2009h. Stimulation with 100\u2009ng\/mL of lipopolysaccharide (LPS) was carried out in parallel as a positive control of CD62\u2010L shedding. CD62\u2010L expression was evaluated by FC using an anti CD62\u2010L\u2010 antibody and down\u2010regulation was assessed by calculating the difference in CD62\u2010L expression before and after stimulation, both in terms of percentage of CD62\u2010L expressing cells (\u0394%CD62\u2010L) and median fluorescence intensity (\u0394MFI%). Neutrophils and monocytes from XIAP deficient patients displayed a significantly diminished response to L18\u2010MDP stimulation compared with HC (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), indicating a severely altered mechanism of CD62\u2010L down\u2010regulation following activation of NOD2\u2010XIAP axis. On the other hand, the response to LPS stimulation was comparable between patients and heathy controls, suggesting preserved CD62\u2010L shedding with a different stimulus. FC detection of CD62\u2010L down\u2010regulation in monocytes and neutrophils after whole blood stimulation with L18\u2010MDP results in an effective and rapid functional test for the identification of XIAP deficient patients.<\/jats:p>","DOI":"10.1002\/cyto.b.22181","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T09:59:49Z","timestamp":1716285589000},"page":"383-391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>CD62\u2010L<\/scp> down\u2010regulation after <scp>L18\u2010MDP<\/scp> stimulation as a complementary flow cytometry functional assay for the diagnosis of <scp>XIAP<\/scp> deficiency"],"prefix":"10.1002","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4071-0739","authenticated-orcid":false,"given":"Agust\u00edn D.","family":"Rizzo","sequence":"first","affiliation":[{"name":"Laboratory Division, Cellular Immunology Laboratory Hospital de Pediatr\u00eda S.A.M.I.C. Prof. Dr. Juan P. Garrahan  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianela","family":"Sanz","sequence":"additional","affiliation":[{"name":"Laboratory Division, Cellular Immunology Laboratory Hospital de Pediatr\u00eda S.A.M.I.C. Prof. Dr. Juan P. Garrahan  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgina","family":"Roffe","sequence":"additional","affiliation":[{"name":"Laboratory Division, Cellular Immunology Laboratory Hospital de Pediatr\u00eda S.A.M.I.C. Prof. Dr. Juan P. Garrahan  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa O.","family":"Sajaroff","sequence":"additional","affiliation":[{"name":"Laboratory Division, Cellular Immunology Laboratory Hospital de Pediatr\u00eda S.A.M.I.C. Prof. Dr. Juan P. Garrahan  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damian A.","family":"Prado","sequence":"additional","affiliation":[{"name":"Laboratory Division, Cellular Immunology Laboratory Hospital de Pediatr\u00eda S.A.M.I.C. Prof. Dr. Juan P. Garrahan  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Prieto","sequence":"additional","affiliation":[{"name":"Immunology and Rheumatology Division, Molecular Immunology Laboratory Hospital de Pediatr\u00eda S.A.M.I.C. Prof. Dr. Juan P. Garrahan  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ver\u00f3nica","family":"Goris","sequence":"additional","affiliation":[{"name":"Immunology and Rheumatology Division, Molecular Immunology Laboratory Hospital de Pediatr\u00eda S.A.M.I.C. Prof. Dr. Juan P. Garrahan  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge G.","family":"Rossi","sequence":"additional","affiliation":[{"name":"Laboratory Division, Cellular Immunology Laboratory Hospital de Pediatr\u00eda S.A.M.I.C. Prof. Dr. Juan P. Garrahan  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea R.","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Laboratory Division, Cellular Immunology Laboratory Hospital de Pediatr\u00eda S.A.M.I.C. Prof. Dr. Juan P. Garrahan  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.04.031"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.02.028"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12306"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.09.002"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjac124"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(97)00157-9"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.1059686"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjab013"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2009.03212.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00734.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408363.2014.881317"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2009.81"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-015-0166-0"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2017.01.001"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12307"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.988862"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2010.08.010"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-290-2_15"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-256099"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008072200"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl15176"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00532"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2652-4"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05257"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-328849"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-021-01188-z"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.01.024"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-1845"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-015-0144-6"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-306520"}],"container-title":["Cytometry Part B: Clinical Cytometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cyto.b.22181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T07:30:18Z","timestamp":1727681418000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cyto.b.22181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,21]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/cyto.b.22181"],"URL":"https:\/\/doi.org\/10.1002\/cyto.b.22181","archive":["Portico"],"relation":{},"ISSN":["1552-4949","1552-4957"],"issn-type":[{"value":"1552-4949","type":"print"},{"value":"1552-4957","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,21]]},"assertion":[{"value":"2023-09-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}