Complement Factor H Regulates a Complement-Extracellular Vesicle-Macrophage Axis in Immune Mediated Kidney Injury.

Introduction

Complement Factor H (FH) regulates the alternative complement pathway, and FH deficiency promotes complement activation, macrophage recruitment, and renal injury. Extracellular vesicles (EVs) mediate intercellular communication and may provide molecular signatures of tissue inflammation.

Methods

We examined complement- and macrophage-associated transcriptional signatures in renal tissue and serum-, kidney-, and urine-derived EVs using a FH-deficient murine model of chronic serum sickness. Pilot kidney microarray analysis was combined with qRT-PCR and EV transcript profiling.

Results

FH deficiency increased renal expression of macrophage-associated inflammatory genes, including AIF1, MMP9, S100A10, and CD44, and the complement receptor C3aR1. EVs from FH-deficient mice lacked FH transcripts and exhibited increased complement- and macrophage-associated transcripts across serum-, kidney-, and urine-derived EV populations. EV transcriptional profiles paralleled inflammatory gene expression observed in renal tissue.Discussion: FH deficiency-associated complement dysregulation produces coordinated inflammatory transcriptional signatures detectable in both kidney tissue and EVs. The concordance between intrarenal inflammatory programs and EV cargo suggests that EVs may reflect complement-mediated renal immune activity. In particular, urinary EVs may provide a non-invasive source of molecular information and potential biomarkers of complement-mediated kidney inflammation.