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The aim of this work was to describe the prevalence of IgG anti-IgA and its association with HS, and to explore a new pathophysiological hypothesis involving the complement system. We measured IgG anti-IgA, using a standardised commercial technique, in controls and PID patients, and compared our results to a systematic literature review. We measured complement activation in PID patients before and after IgP infusion, and in vitro after incubation of IgP with serum from controls and PID patients. IgG anti-IgA was detected in 6% (<jats:italic>n<\/jats:italic>\u2009=\u20092\/32) of PID patients, 30% (<jats:italic>n<\/jats:italic>\u2009=\u20093\/10) of selective IgA deficiency patients and 2% (<jats:italic>n<\/jats:italic>\u2009=\u20091\/46) of healthy controls. In the literature and our study, 38 PID patients had IgG anti-IgA and HS to IgPs and 9 had IgG anti-IgA but good tolerance to IgPs. In our patients, we observed a constant complement activation after IgP infusion compared to baseline. In vitro, IgP induced significant complement activation with all sera from tested individuals. IgA immunisation is not rare in PID, higher in selective IgA deficiency, but may also occur in healthy controls. Our results question the clinical relevance and pathophysiological implication of IgG anti-IgA in the context of HS with IgPs. Complement activation-related pseudoallergy could explain the clinical characteristics and natural history of HS symptoms.<\/jats:p>","DOI":"10.1007\/s12016-024-09007-0","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T14:02:33Z","timestamp":1729605753000},"page":"47-57","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Non-allergic Hypersensitivity Reactions to Immunoglobulin Preparations in Antibody Deficiencies: What Role for Anti-IgA IgG and Complement Activation?"],"prefix":"10.1007","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8279-1912","authenticated-orcid":false,"given":"Aurore","family":"Collet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane Pelletier","family":"de Chambure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Moitrot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00eblle","family":"Breyne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriane","family":"Mirgot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Rogeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Tronchon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Nicolas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Sanges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Stabler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Ledoult","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Terriou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Launay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hachulla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Labalette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Dubucquoi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Lef\u00e8vre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"issue":"6","key":"9007_CR1","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1542\/peds.9.6.722","volume":"9","author":"OC Bruton","year":"1952","unstructured":"Bruton OC (1952) Agammaglobulinemia. 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The data and the patients\u2019 sample collections were declared to the CNIL (DEC24-089).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"In line with the regulations laid down by the French National Data Protection Commission (CNIL) and international guidelines, written, informed consent was neither required nor requested for this non-interventional study. The patients received by mail an information letter about the study and a non-opposition notice, and had the opportunity to refuse their inclusion.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"No identifying individual participants\u2019 data are included in this manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"Guillaume Lef\u00e8vre has received honoraria for serving on the board and for participating in symposia from Takeda, LFB, Griffols, research support from LFB, Takeda, CSL Behring, Biotest, Octapharma. David Launay has received honoraria for board or symposia from Takeda, Biocryst, Astra-Zeneca and CSL Behring, and research support from CSL Behring, and Octapharma. Emmanuel Ledoult has received consulting and personal fees from Takeda, Grifols, GSK and Astra-Zeneca.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}