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Testing the Activit...
Testing the Activity of Complement Convertases in Serum/Plasma for Diagnosis of C4NeF-Mediated C3 Glomerulonephritis
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- Blom, Anna M. (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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- Corvillo, Fernando (author)
- University Hospital La Paz
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Magda, Michal (author)
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- Stasiłojć, Grzegorz (author)
- Medical University of Gdansk
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- Nozal, Pilar (author)
- Biomedical Network on Rare Diseases (CIBERER)
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- Pérez-Valdivia, Miguel Ángel (author)
- University Hospital Virgen del Rocío
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- Cabello-Chaves, Virginia (author)
- University Hospital Virgen del Rocío
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- Rodríguez de Córdoba, Santiago (author)
- Biological Research Center (CIB), Madrid
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- López-Trascasa, Margarita (author)
- Biomedical Network on Rare Diseases (CIBERER)
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- Okrój, Marcin (author)
- Medical University of Gdansk
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(creator_code:org_t)
- 2016-05-05
- 2016
- English.
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In: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; , s. 517-527
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Abstract
Subject headings
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- Autoantibodies termed C3-nephritic factor (C3NeF), which stabilize convertases of the alternative complement pathway, often stimulate autoinflammatory diseases. However, knowledge about analogous autoantibodies acting on the classical pathway (C4NeF) is limited to a few reports, which indicate association with kidney dysfunction, systemic lupus erythematous, and infections. C4NeF may appear independently from C3NeF, but the lack of a routine diagnostic method predisposes C4NeF for being an underestimated player in autoinflammatory episodes. We tested the activity of classical convertases directly in serum/plasma to screen samples from 13 patients with C3 glomerulopathies and identified one patient showing significantly prolonged half-life of these enzymes. Observed effect was reproduced by immunoglobulins purified from patient’s plasma and additionally confirmed on classical convertase built from purified components. Isolated immunoglobulins protected classical convertases from both spontaneous and inhibitor-driven decay but not from C4b proteolysis. The patient had a decreased serum level of C3, elevated sC5b-9, and normal concentrations of factor B and C4. Neither C3NeF nor other autoantibodies directed against alternative pathway proteins (factor H, factor B, factor I, C3, and properdin) were found. Genetic analysis showed no mutations in C3, CFB, CFH, CFI, MCP, THBD, and DGKE genes. Renal biopsy revealed a membranoproliferative pattern with intense C3 deposits. Our results underline the importance of C4NeF as an independent pathogenic factor and a need for the implementation of routine examination of classical convertase activity. Proposed method may enable robust inspection of such atypical cases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- C3 glomerulonephritis
- C4NeF
- complement convertase
- Complement system
Publication and Content Type
- art (subject category)
- ref (subject category)
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