Complement Factor H-Related Protein 4A Is the Dominant Circulating Splice Variant of CFHR4

Pouw, Richard B. and Brouwer, Mieke C. and van Beek, Anna E. and Józsi, Mihály and Wouters, Diana and Kuijpers, Taco W.. (2018) Complement Factor H-Related Protein 4A Is the Dominant Circulating Splice Variant of CFHR4. Frontiers in Immunology, 9. p. 729.

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Official URL: https://edoc.unibas.ch/70304/

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Recent research has elucidated circulating levels of almost all factor H-related (FHR) proteins. Some of these proteins are hypothesized to act as antagonists of the important complement regulator factor H (FH), fine-tuning complement regulation on human surfaces. For the; CFHR4; splice variants FHR-4A and FHR-4B, the individual circulating levels are unknown, with only total levels being described. Specific reagents for FHR-4A or FHR-4B are lacking due to the fact that the unique domains in FHR-4A show high sequence similarity with FHR-4B, making it challenging to distinguish them. We developed an assay that specifically measures FHR-4A using novel, well-characterized monoclonal antibodies (mAbs) that target unique domains in FHR-4A only. Using various FHR-4A/FHR-4B-specific mAbs, no FHR-4B was identified in any of the serum samples tested. The results demonstrate that FHR-4A is the dominant splice variant of; CFHR4; in the circulation, while casting doubt on the presence of FHR-4B. FHR-4A levels (avg. 2.55 ± 1.46 µg/mL) were within the range of most of the previously reported levels for all other FHRs. FHR-4A was found to be highly variable among the population, suggesting a strong genetic regulation. These results shed light on the physiological relevance of the previously proposed role of FHR-4A and FHR-4B as antagonists of FH in the circulation.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molekulare Pharmazie (Ricklin)
UniBasel Contributors:Pouw, Richard Benjamin
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Frontiers Media
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2019 10:27
Deposited On:08 May 2019 10:25

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