{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:12:14Z","timestamp":1793315534701,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["PI19\/00970"],"award-info":[{"award-number":["PI19\/00970"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["PI16\/00723"],"award-info":[{"award-number":["PI16\/00723"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Haemolytic Uraemic Syndrome associated with<jats:italic>Streptococcus pneumoniae<\/jats:italic>infections (SP-HUS) is a clinically well-known entity that generally affects infants, and could have a worse prognosis than HUS associated to<jats:italic>E. coli<\/jats:italic>infections. It has been assumed that complement genetic variants associated with primary atypical HUS cases (aHUS) do not contribute to SP-HUS, which is solely attributed to the action of the pneumococcal neuraminidase on the host cellular surfaces. We previously identified complement pathogenic variants and risk polymorphisms in a few Hungarian SP-HUS patients, and have now extended these studies to a cohort of 13 Spanish SP-HUS patients. Five patients presented rare complement variants of unknown significance, but the frequency of the risk haplotypes in the<jats:italic>CFH-CFHR3-CFHR1<\/jats:italic>region was similar to the observed in aHUS. Moreover, we observed desialylation of Factor H (FH) and the FH-Related proteins in plasma samples from 2 Spanish and 4 Hungarian SP-HUS patients. To analyze the functional relevance of this finding, we compared the ability of native and \u201c<jats:italic>in vitro<\/jats:italic>\u201d desialylated FH in: (a) binding to C3b-coated microtiter plates; (b) proteolysis of fluid-phase and surface-bound C3b by Factor I; (c) dissociation of surface bound-C3bBb convertase; (d) haemolytic assays on sheep erythrocytes. We found that desialylated FH had reduced capacity to control complement activation on sheep erythrocytes, suggesting a role for FH sialic acids on binding to cellular surfaces. We conclude that aHUS-risk variants in the<jats:italic>CFH-CFHR3-CFHR1<\/jats:italic>region could also contribute to disease-predisposition to SP-HUS, and that transient desialylation of complement FH by the pneumococcal neuraminidase may have a role in disease pathogenesis.<\/jats:p>","DOI":"10.3389\/fimmu.2021.641656","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T07:54:36Z","timestamp":1615449276000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Complement Genetic Variants and FH Desialylation in S. pneumoniae-Haemolytic Uraemic Syndrome"],"prefix":"10.3389","volume":"12","author":[{"given":"Irene","family":"G\u00f3mez 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