{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:07:33Z","timestamp":1791400053903,"version":"4.3.3"},"reference-count":12,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,28]],"date-time":"2015-01-28T00:00:00Z","timestamp":1422403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We previously reported that p.Ser707Tyr, a novel variant in phospholipase C\u03b32 (PLC\u03b32), is the cause of a dominantly inherited autoinflammatory disease, autoinflammation and PLC\u03b32\u2010associated antibody deficiency and immune dysregulation (APLAID). The hypermorphic mutation enhances PLC\u03b32 activity and causes an increase in intracellular Ca<jats:sup>2+<\/jats:sup> release from endoplasmic reticulum stores. Because increased intracellular Ca<jats:sup>2+<\/jats:sup> signaling has been associated with NLRP3 inflammasome activation, we studied the role of the NLRP3 inflammasome in the pathogenesis of APLAID.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human peripheral blood mononuclear cells (PBMCs) were isolated from healthy control subjects and 2 patients with APLAID. Inflammasome activation was analyzed by Western blotting. Intracellular Ca<jats:sup>2+<\/jats:sup> levels were measured with a FLIPR Calcium 4 assay kit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cells from the patients had elevated basal levels of intracellular Ca<jats:sup>2+<\/jats:sup>, and the intracellular Ca<jats:sup>2+<\/jats:sup> flux triggered by extracellular CaCl<jats:sub>2<\/jats:sub> was substantially enhanced. Patient PBMCs secreted interleukin\u20101\u03b2 in response to lipopolysaccharide priming alone, and this effect was attenuated by treatment with a PLC inhibitor, intracellular Ca<jats:sup>2+<\/jats:sup> blockers, or an adenylate cyclase activator.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that the inflammation in patients with APLAID is partially driven by activation of the NLRP3 inflammasome. These data link 2 seemingly distinct molecular pathways and provide new insights into the pathogenesis of APLAID and autoinflammation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38961","type":"journal-article","created":{"date-parts":[[2014,11,21]],"date-time":"2014-11-21T15:19:54Z","timestamp":1416583194000},"page":"563-567","source":"Crossref","is-referenced-by-count":80,"title":["Brief Report: Connecting Two Pathways Through Ca<sup>2+<\/sup> Signaling: NLRP3 Inflammasome Activation Induced by a Hypermorphic <i>PLCG2<\/i> Mutation"],"prefix":"10.1002","volume":"67","author":[{"given":"Jae Jin","family":"Chae","sequence":"first","affiliation":[{"name":"National Human Genome Research Institute, NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung","family":"Park","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il\u2010Young","family":"Hwang","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Kehrl","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivona","family":"Aksentijevich","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Kastner","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37882"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.08.006"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.6.2095.bloodjournal8762095"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.040"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng756"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10688"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11588"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04516"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2279"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1831"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08938"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1636"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.38961","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.38961","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.38961","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.38961","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T18:45:08Z","timestamp":1759949108000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.38961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,28]]},"references-count":12,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,2]]}},"alternative-id":["10.1002\/art.38961"],"URL":"https:\/\/doi.org\/10.1002\/art.38961","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,28]]}}}