Potency measurements of the complement system facilitated by antibodies targeting the zymogen form of complement factor D (Adipsin)

TY - JOUR

T1 - Potency measurements of the complement system facilitated by antibodies targeting the zymogen form of complement factor D (Adipsin)

AU - Palarasah, Yaseelan

AU - Henriksen, Anne Sofie Løgstrup

AU - Thiel, Steffen

AU - Henriksen, Maiken

AU - Hansen, Søren W.K.

N1 - Publisher Copyright: © 2022 The Authors

PY - 2022/6

Y1 - 2022/6

N2 - The serine protease complement factor D is fundamental in the activation of the complement system. In addition, it was the first adipokine described (named Adipsin) and shown to improve beta cell function in diabetes. As part of an amplification loop of complement activation, factor D is a rate-limiting enzyme, and its accessibility contributes to the potency of complement activation. The dogma has been that conversion of the zymogen form, profactor D, to mature factor D occurred during secretion by adipocytes by uncharacterized proteases. However, recent findings demonstrated that the serine protease MASP-3 of the lectin pathway of the complement system mediated this conversion, suggesting that pattern recognition of pathogen/danger-associated molecular patterns could be a prior requirement for all complement activation. To facilitate studies addressing this hypothesis, we have developed monoclonal antibodies specific for human profactor D without binding to mature factor D. We demonstrate their applications in accessing the conversion of profactor D into mature factor D and in measuring levels of profactor D.

AB - The serine protease complement factor D is fundamental in the activation of the complement system. In addition, it was the first adipokine described (named Adipsin) and shown to improve beta cell function in diabetes. As part of an amplification loop of complement activation, factor D is a rate-limiting enzyme, and its accessibility contributes to the potency of complement activation. The dogma has been that conversion of the zymogen form, profactor D, to mature factor D occurred during secretion by adipocytes by uncharacterized proteases. However, recent findings demonstrated that the serine protease MASP-3 of the lectin pathway of the complement system mediated this conversion, suggesting that pattern recognition of pathogen/danger-associated molecular patterns could be a prior requirement for all complement activation. To facilitate studies addressing this hypothesis, we have developed monoclonal antibodies specific for human profactor D without binding to mature factor D. We demonstrate their applications in accessing the conversion of profactor D into mature factor D and in measuring levels of profactor D.

KW - Adipsin

KW - Complement factor D

KW - Lectin pathway

KW - MASP-3

UR - http://www.scopus.com/inward/record.url?scp=85128226597&partnerID=8YFLogxK

U2 - 10.1016/j.molimm.2022.04.002

DO - 10.1016/j.molimm.2022.04.002

M3 - Journal article

C2 - 35429907

AN - SCOPUS:85128226597

SN - 0161-5890

VL - 146

SP - 46

EP - 49

JO - Molecular immunology

JF - Molecular immunology

ER -