C2 by-pass: cross-talk between the complement classical and alternative pathways

Laich, A., Patel, H., Zarantonello, A., Sim, R.B. and Inal, J.M. 2022. C2 by-pass: cross-talk between the complement classical and alternative pathways. Immunobiology. 227 (3) 152225. https://doi.org/10.1016/j.imbio.2022.152225

TitleC2 by-pass: cross-talk between the complement classical and alternative pathways
TypeJournal article
AuthorsLaich, A., Patel, H., Zarantonello, A., Sim, R.B. and Inal, J.M.
Abstract

Several disorders associated with the total or partial absence of components of the human complement system are known. Deficiencies of classical pathway (CP) components are generally linked to systemic lupus erythematosus (SLE) or SLE-like syndromes. However, only approximately one-third of patients who lack C2 show mild symptoms of SLE. The relatively high frequency of homozygous C2 deficiency without or with minor disease manifestation suggests that there might be a compensatory mechanism which allows the activation of the CP of complement without the absolute requirement of C2. In this study we show that factor B (FB), the C2 homologue of the alternative pathway (AP) of complement, can substitute for C2. This was confirmed by using C4b as immobilised ligand and FB as analyte in Surface Plasmon Resonance (BIACORE). C2 binding to the immobilised C3b-like molecule C3(CH3NH2) was not seen. The estimated binding constant for C4bB complex formation was 2.00 * 10−5 [M]. We were further able to demonstrate that C4b supports the cleavage of Factor B by Factor D. Finally, cleavage of 125I-C3 by C4bBb was evaluated and gave strong evidence that the “hybrid” convertase C4bBb can cleave and activate C3 in vitro. Cleavage activity is very low, but consistent with some of the “C2-bypass” observations of others.

Article number152225
JournalImmunobiology
Journal citation227 (3)
ISSN0171-2985
Year2022
PublisherElsevier
Digital Object Identifier (DOI)https://doi.org/10.1016/j.imbio.2022.152225
Web address (URL)https://www.sciencedirect.com/science/article/pii/S0171298522000511?via%3Dihub
Publication dates
Published05 May 2022

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