dc.creator | Hong, Y. | es |
dc.creator | Nanthapisal, S. | es |
dc.creator | Omoyinmi, E. | es |
dc.creator | Olbrich, Peter | es |
dc.creator | Neth, O. | es |
dc.creator | Speckmann, C. | es |
dc.creator | Lucena, J.M. | es |
dc.creator | Gilmour, K. | es |
dc.creator | Genomics England Res Consortium | es |
dc.creator | Zarowiecki, M. | es |
dc.date.accessioned | 2024-05-21T13:16:11Z | |
dc.date.available | 2024-05-21T13:16:11Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Hong, Y., Nanthapisal, S., Omoyinmi, E., Olbrich, P., Neth, O., Speckmann, C.,...,Zarowiecki, M. (2019). Secondary C1q Deficiency in Activated PI3K delta Syndrome Type 2. Frontiers In Immunology, 10, 2589. https://doi.org/10.3389/fimmu.2019.02589. | |
dc.identifier.issn | 1664-3224 | es |
dc.identifier.uri | https://hdl.handle.net/11441/158753 | |
dc.description.abstract | Monogenic forms of vasculitis are rare but increasingly recognized. Furthermore, genetic
immunodeficiency is increasingly associated with inflammatory immune dysregulatory
features, including vasculitis. This case report describes a child of non-consanguineous
parents who presented with chronic digital vasculitis early in life, is of short stature, has
facial dysmorphia, immunodeficiency (low serum IgA, high serum IgM), recurrent bacterial
infections, lymphoproliferation, absence of detectable serum C1q, and low classical
complement pathway activity. We identified a previously reported de novo heterozygous
pathogenic splice mutation in PIK3R1 (c.1425 + 1G > A), resulting in the skipping of
exon 11 of the p85α subunit of phosphatidylinositol 3-kinase and causing activated
PI3Kδ syndrome type II (APDS2). This explained the phenotype, with the exception of
digital vasculitis and C1q deficiency, which have never been described in association
with APDS2. No mutations were identified in C1QA, B, or C, their promoter regions, or in
any other complement component. Functional studies indicated normal monocytic C1q
production and release, suggesting that the observed C1q deficiency was caused by
peripheral consumption of C1q. Since C1q deficiency has never been associated with
APDS2, we assessed C1q levels in two unrelated patients with genetically confirmed
APDS2 and confirmed C1q deficiency in those two cases as well. This observation
suggests C1q deficiency to be an inherent but previously unrecognized feature of APDS2.
We speculate that the consumption of C1q is driven by increased apoptotic bodies
derived from immune cellular senescence, combined with elevated IgM production
(both inherent features of APDS2). Secondary C1q deficiency in APDS2 may further
contribute to immunodeficiency and could also be associated with inflammatory immune
dysregulatory phenotypes, such as the digital vasculitis observed in our case. | es |
dc.format | application/pdf | es |
dc.format.extent | 8 p. | es |
dc.language.iso | eng | es |
dc.publisher | Frontiers Media S.A. | es |
dc.relation.ispartof | Frontiers In Immunology, 10, 2589. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Digital vasculitis | es |
dc.subject | C1q deficiency | es |
dc.subject | SHORT syndrome | es |
dc.subject | Activated PI3Kδ syndrome type 2 | es |
dc.subject | Hyper-IgM syndrome | es |
dc.subject | Immunodeficiency | es |
dc.title | Secondary C1q Deficiency in Activated PI3K delta Syndrome Type 2 | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología | es |
dc.contributor.affiliation | Instituto de Biomedicina de Sevilla (IBIS) | |
dc.relation.projectID | JR18/00042 | es |
dc.relation.publisherversion | https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02589/full | es |
dc.identifier.doi | 10.3389/fimmu.2019.02589 | es |
dc.journaltitle | Frontiers In Immunology | es |
dc.publication.volumen | 10 | es |
dc.publication.initialPage | 2589 | es |
dc.contributor.funder | Programa Juan Rodes, Instituto de Salud Carlos III | es |