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Peer-reviewedCC BY 4.0Frontiers in Immunology

A commercial C3c ELISA as a diagnostic tool for complete complement factor I deficiency

  • Simon Péter Nagy1
  • Nóra Veszeli1,2
  • Blanka Mező2
  • Sarolta Dobner3
  • Otilia Petrovicova4,5
  • Milos Jesenak4,5
  • Vera Goda6
  • Anikó Szabó7
  • Alíz Zimmermann8
  • Csaba Bereczki8
  • Éva Rákóczi9
  • Boglárka Soós9
2 more authors
  • Ágnes Szilágyi1
  • Zoltán Prohászka1,2
9 affiliations
  1. 1Research Laboratory, Department of Internal Medicine and Hematology, Semmelweis University
  2. 2Research Group of Immunology and Hematology, Hungarian Research Network - Semmelweis University (HUN-REN-SU)
  3. 3Tűzoltó Street Department, Pediatric Center, Semmelweis University
  4. 4Institute of Clinical Immunology and Medical Genetics, Jessenius Faculty of Medicine, Comenius University in Bratislava, University Hospital Martin
  5. 5Department of Paediatrics and Adolescent Medicine, Jessenius Faculty of Medicine, Comenius University in Bratislava, University Hospital Martin
  6. 6Department of Pediatric Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest
  7. 7Albert Szent-Györgyi Health Centre, Department of Rheumatology and Immunology, University of Szeged
  8. 8Albert Szent-Györgyi Health Centre, Department of Pediatrics and Pediatric Health Center, University of Szeged
  9. 9Department of Rheumatology, Faculty of Medicine, University of Debrecen
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Abstract

Complete complement Factor I (FI) deficiency is an ultra-rare inborn error of immunity characterized by invasive encapsulated bacterial infections and/or sterile neuroinflammation (DEFICIT syndrome). Acute episodes can progress rapidly to life-threatening illness, so prompt diagnosis is critical. Genetic confirmation is time-consuming; antigenic FI quantification is blind to qualitative (type II) variants; and the consumptive profile is mimicked by other complement deficiencies and secondary consumptive states. Functional readouts have been proposed: because C3 and C4 cleavage fragments arise downstream of FI, their absence reports loss of FI function irrespective of variant class. Commercial assays have not been compared for this purpose, so we assessed whether they distinguish complete FI deficiency from these mimics. We measured C3c, C3d, C4d and iC3b in EDTA plasma from six genetically confirmed FI-deficient patients and 52 controls comprising other complement deficiencies, consumptive states, and healthy individuals. C3c and C4d were also measured in serum. Only C3c separated complete FI deficiency from every comparator. Plasma C3c was below the quantification limit (160 ng/mL) in all patients, whereas all controls were quantifiable (lowest 394 ng/mL). Serum reproduced the separation, including in two patients with type II variants. C4d was unquantifiable in patients, but the low control baseline left no reliable cut-off. C3d and iC3b were elevated rather than reduced, suggesting possible cross-reactivity with C3b-containing complexes. A commercial C3c ELISA provides a rapid functional readout of FI activity, independent of variant class and applicable in serum. It could support earlier triage of suspected cases while genetic confirmation is pending.

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Cite

BibTeXRIS
BibTeX
@article{nagy2026commercial,
  title = {{A commercial C3c ELISA as a diagnostic tool for complete complement factor I deficiency}},
  author = {Simon Péter Nagy and Nóra Veszeli and Blanka Mező and Sarolta Dobner and Otilia Petrovicova and Milos Jesenak and Vera Goda and Anikó Szabó and Alíz Zimmermann and Csaba Bereczki and Éva Rákóczi and Boglárka Soós and Ágnes Szilágyi and Zoltán Prohászka},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1992421},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1992421/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A commercial C3c ELISA as a diagnostic tool for complete complement factor I deficiency
AU  - Simon Péter Nagy
AU  - Nóra Veszeli
AU  - Blanka Mező
AU  - Sarolta Dobner
AU  - Otilia Petrovicova
AU  - Milos Jesenak
AU  - Vera Goda
AU  - Anikó Szabó
AU  - Alíz Zimmermann
AU  - Csaba Bereczki
AU  - Éva Rákóczi
AU  - Boglárka Soós
AU  - Ágnes Szilágyi
AU  - Zoltán Prohászka
PY  - 2026
DA  - 2026/10/29
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1992421
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1992421/full
AB  - Complete complement Factor I (FI) deficiency is an ultra-rare inborn error of immunity characterized by invasive encapsulated bacterial infections and/or sterile neuroinflammation (DEFICIT syndrome). Acute episodes can progress rapidly to life-threatening illness, so prompt diagnosis is critical. Genetic confirmation is time-consuming; antigenic FI quantification is blind to qualitative (type II) variants; and the consumptive profile is mimicked by other complement deficiencies and secondary consumptive states. Functional readouts have been proposed: because C3 and C4 cleavage fragments arise downstream of FI, their absence reports loss of FI function irrespective of variant class. Commercial assays have not been compared for this purpose, so we assessed whether they distinguish complete FI deficiency from these mimics. We measured C3c, C3d, C4d and iC3b in EDTA plasma from six genetically confirmed FI-deficient patients and 52 controls comprising other complement deficiencies, consumptive states, and healthy individuals. C3c and C4d were also measured in serum. Only C3c separated complete FI deficiency from every comparator. Plasma C3c was below the quantification limit (160 ng/mL) in all patients, whereas all controls were quantifiable (lowest 394 ng/mL). Serum reproduced the separation, including in two patients with type II variants. C4d was unquantifiable in patients, but the low control baseline left no reliable cut-off. C3d and iC3b were elevated rather than reduced, suggesting possible cross-reactivity with C3b-containing complexes. A commercial C3c ELISA provides a rapid functional readout of FI activity, independent of variant class and applicable in serum. It could support earlier triage of suspected cases while genetic confirmation is pending.
SN  - 1664-3224
ER  -