Novel immunochromatographic test for rapid detection of anti-factor H autoantibodies with an assessment of its clinical relevance
Factor H (FH) is a crucial complement regulator that prevents complement-mediated injury to healthy cells and tissues. This regulatory function can be disrupted by Factor H autoantibodies (FHAA), which then leads to diseases such as atypical hemolytic uremic syndrome (aHUS) and C3 Glomerulopathy (C3...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1527016/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832589829171314688 |
|---|---|
| author | Santiago Rodríguez de Córdoba Andrea Reparaz Daniel Sanchez Sheila Pinto Lucia Juana Lopez Héctor Martin Merinero Iria Calvete Julian Perez-Perez Sydney S. Jellison Yuzhou Zhang Richard J. H. Smith Inmaculada Moreno Mercedes Dominguez |
| author_facet | Santiago Rodríguez de Córdoba Andrea Reparaz Daniel Sanchez Sheila Pinto Lucia Juana Lopez Héctor Martin Merinero Iria Calvete Julian Perez-Perez Sydney S. Jellison Yuzhou Zhang Richard J. H. Smith Inmaculada Moreno Mercedes Dominguez |
| author_sort | Santiago Rodríguez de Córdoba |
| collection | DOAJ |
| description | Factor H (FH) is a crucial complement regulator that prevents complement-mediated injury to healthy cells and tissues. This regulatory function can be disrupted by Factor H autoantibodies (FHAA), which then leads to diseases such as atypical hemolytic uremic syndrome (aHUS) and C3 Glomerulopathy (C3G). In pediatric aHUS, the FHAA incidence is ~10-15%, although in the Indian population, it rises to ~50%. The specific regions of FH targeted by FHAAs correlate with the pathogenic mechanism of the associated disease. In aHUS, FHAAs target the C-terminus, thereby impacting FH ability to recognize cell surfaces. In C3G, in contrast, FHAAs often target the N-terminus, generating an acquired functional FH deficiency. Detection and monitoring FHAAs are decisive for effectively treating patients. Current FHAA analysis normally identify free FHAAs that bind surface-bound FH using ELISA techniques. These methods require well-equipped laboratories and qualified staff, and do not measure FH-FHAA complexes, which can make it difficult to correlate titers with clinical outcomes. The visually-based immunochromatographic test (ICT) described herein allows for quick detection and quantification of IgG and IgM FH-FHAA complexes in human EDTA-plasma or serum. This ICT offers improved detection of FHAAs compared to ELISA as demonstrated by cases where the ICT identifies FH-FHAA complexes in samples that tested negative with the free FHAA ELISA. Importantly, the ICT indirectly informs on the amount of FH that is complexed with FHAAs, thus assessing the significance of the FHAA in disrupting the regulatory function of FH. Overall, this novel assay offers a simple, fast, cost-effective, and, likely, more clinically relevant alternative for diagnosing FHAAs in at-risk populations. |
| format | Article |
| id | doaj-art-36cecd1610754f6aabf888e602e40fea |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-36cecd1610754f6aabf888e602e40fea2025-01-24T07:13:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15270161527016Novel immunochromatographic test for rapid detection of anti-factor H autoantibodies with an assessment of its clinical relevanceSantiago Rodríguez de Córdoba0Andrea Reparaz1Daniel Sanchez2Sheila Pinto3Lucia Juana Lopez4Héctor Martin Merinero5Iria Calvete6Julian Perez-Perez7Sydney S. Jellison8Yuzhou Zhang9Richard J. H. Smith10Inmaculada Moreno11Mercedes Dominguez12Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior Investigaciones Científicas (CSIC), Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior Investigaciones Científicas (CSIC), Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior Investigaciones Científicas (CSIC), Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior Investigaciones Científicas (CSIC), Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior Investigaciones Científicas (CSIC), Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior Investigaciones Científicas (CSIC), Madrid, SpainSecugen S. L., Madrid, SpainSecugen S. L., Madrid, SpainMolecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesMolecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesMolecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesUnidad de Inmunología Microbiana, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, SpainUnidad de Inmunología Microbiana, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, SpainFactor H (FH) is a crucial complement regulator that prevents complement-mediated injury to healthy cells and tissues. This regulatory function can be disrupted by Factor H autoantibodies (FHAA), which then leads to diseases such as atypical hemolytic uremic syndrome (aHUS) and C3 Glomerulopathy (C3G). In pediatric aHUS, the FHAA incidence is ~10-15%, although in the Indian population, it rises to ~50%. The specific regions of FH targeted by FHAAs correlate with the pathogenic mechanism of the associated disease. In aHUS, FHAAs target the C-terminus, thereby impacting FH ability to recognize cell surfaces. In C3G, in contrast, FHAAs often target the N-terminus, generating an acquired functional FH deficiency. Detection and monitoring FHAAs are decisive for effectively treating patients. Current FHAA analysis normally identify free FHAAs that bind surface-bound FH using ELISA techniques. These methods require well-equipped laboratories and qualified staff, and do not measure FH-FHAA complexes, which can make it difficult to correlate titers with clinical outcomes. The visually-based immunochromatographic test (ICT) described herein allows for quick detection and quantification of IgG and IgM FH-FHAA complexes in human EDTA-plasma or serum. This ICT offers improved detection of FHAAs compared to ELISA as demonstrated by cases where the ICT identifies FH-FHAA complexes in samples that tested negative with the free FHAA ELISA. Importantly, the ICT indirectly informs on the amount of FH that is complexed with FHAAs, thus assessing the significance of the FHAA in disrupting the regulatory function of FH. Overall, this novel assay offers a simple, fast, cost-effective, and, likely, more clinically relevant alternative for diagnosing FHAAs in at-risk populations.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1527016/fullanti factor H autoantibodiesimmunochromatographic testcomplementatypical hemolytic uremic syndromeC3-glomerulopathydiagnostic test |
| spellingShingle | Santiago Rodríguez de Córdoba Andrea Reparaz Daniel Sanchez Sheila Pinto Lucia Juana Lopez Héctor Martin Merinero Iria Calvete Julian Perez-Perez Sydney S. Jellison Yuzhou Zhang Richard J. H. Smith Inmaculada Moreno Mercedes Dominguez Novel immunochromatographic test for rapid detection of anti-factor H autoantibodies with an assessment of its clinical relevance Frontiers in Immunology anti factor H autoantibodies immunochromatographic test complement atypical hemolytic uremic syndrome C3-glomerulopathy diagnostic test |
| title | Novel immunochromatographic test for rapid detection of anti-factor H autoantibodies with an assessment of its clinical relevance |
| title_full | Novel immunochromatographic test for rapid detection of anti-factor H autoantibodies with an assessment of its clinical relevance |
| title_fullStr | Novel immunochromatographic test for rapid detection of anti-factor H autoantibodies with an assessment of its clinical relevance |
| title_full_unstemmed | Novel immunochromatographic test for rapid detection of anti-factor H autoantibodies with an assessment of its clinical relevance |
| title_short | Novel immunochromatographic test for rapid detection of anti-factor H autoantibodies with an assessment of its clinical relevance |
| title_sort | novel immunochromatographic test for rapid detection of anti factor h autoantibodies with an assessment of its clinical relevance |
| topic | anti factor H autoantibodies immunochromatographic test complement atypical hemolytic uremic syndrome C3-glomerulopathy diagnostic test |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1527016/full |
| work_keys_str_mv | AT santiagorodriguezdecordoba novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance AT andreareparaz novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance AT danielsanchez novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance AT sheilapinto novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance AT luciajuanalopez novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance AT hectormartinmerinero novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance AT iriacalvete novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance AT julianperezperez novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance AT sydneysjellison novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance AT yuzhouzhang novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance AT richardjhsmith novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance AT inmaculadamoreno novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance AT mercedesdominguez novelimmunochromatographictestforrapiddetectionofantifactorhautoantibodieswithanassessmentofitsclinicalrelevance |