C1q as a target molecule to treat human disease: What do mouse studies teach us?

Abstract

The complement system is a field of growing interest for pharmacological intervention. Complement protein C1q, the pattern recognition molecule at the start of the classical pathway of the complement cascade, is a versatile molecule with additional non-canonical actions affecting numerous cellular processes. Based on observations made in patients with hereditary C1q deficiency, C1q is protective against systemic autoimmunity and bacterial infections. Accordingly, C1q deficient mice reproduce this phenotype with susceptibility to autoimmunity and infections. At the same time, beneficial effects of C1q deficiency on disease entities such as neurodegenerative diseases have also been described in murine disease models. This systematic review provides an overview of all currently available literature on the C1q knockout mouse in disease models to identify potential target diseases for treatment strategies focusing on C1q, and discusses potential side-effects when depleting and/or inhibiting C1q.

Keywords: C1q; complement; deficiency; disease; knockout mouse.

Figure 1

Flow diagram of included articles. Flowchart of number of included articles after database query of PubMed and Embase with search terms “complement C1q”, AND “mouse”. Four articles were included based on reference research of cited articles. Articles were initially screened by title and abstract to meet the inclusion criteria (in vivo use of C1qKO mouse, investigated disease model). 177 articles underwent full text review. Thirty-two publications did not fulfill the criteria.

Figure 2

Schematic overview of the proposed effect of C1q deficiency on human disease based on the outcome of studies performed in murine disease models. Beneficial effects are colored in turquoise, detrimental in ocher, and outcomes without general trend or with ambiguous results in grey. The size of the colored area and the underlying pie chart illustrate the number of studies performed in the respective area. MS multiple sclerosis, I/R ischemia and reperfusion, SLE systemic lupus erythematosus.