Abstract
Defective complement activation has been associated with various types of kidney disease. This led to the hypothesis that specific urine complement fragments may be associated with kidney disease etiologies, and disease progression may be reflected by changes in these complement fragments. We investigated the occurrence of complement fragments in urine, their association with kidney function and disease etiology in 16,027 subjects, using mass spectrometry based peptidomics data from the Human Urinary Proteome/Peptidome Database. Twenty-three different urinary peptides originating from complement proteins C3, C4 and factor B (CFB) could be identified. Most C3-derived peptides showed inverse association with estimated glomerular filtration rate (eGFR), while the majority of peptides derived from CFB demonstrated positive association with eGFR. Several peptides derived from the complement proteins C3, C4 and CFB were found significantly associated with specific kidney disease etiologies. These peptides may depict disease-specific complement activation and could serve as non-invasive biomarkers to support development of complement interventions through assessing complement activity for patients’ stratification and monitoring of drug impact. Further investigation of these complement peptides may provide additional insight into disease pathophysiology and could possibly guide therapeutic decisions, especially when targeting complement factors.
Highlights
A total of 23 complement fragments could be identified with high confidence in human urine
Tandem mass spectra from all 23 peptides are shown in Supplementary Figure S1
Due to the high levels of excretion of complement C3-derived peptides in IgA nephropathy (IgAN) and the availability of a substantial number of follow-up data, we investigated the correlation could be detected for C4 and factor B (CFB)
Summary
The urinary proteome holds information on disease and disease pathophysiology [1]. Significant association of specific urinary peptides was demonstrated in large studies that. The complement system is a crucial effector of the innate immune system and involved in mechanisms of the adaptive immune system. It is activated via 3 different pathways, comprised of over 30 different plasma or membrane-bound proteins [11,12]. The complement system is increasingly recognized as an important mediator in the context of kidney diseases [13]. Immune complexes are strong activators of the classical complement pathway and are involved in various forms of glomerulonephritis, e.g., lupus nephritis (LN)
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