Distinct serum proteome profiles associated with collagen-induced arthritis, and complete Freund's adjuvant-induced inflammation in CD38–/– mice

Abstract

Collagen-type-II-induced arthritis (CIA) is milder in CD38-/- than in WT mice. Their serum samples were treated with ProteoMiner-beads to equalize protein concentrations resulting in a signifi cant enrichment in proteins from extracellular vesicles (blood microparticles, exosomes). ProteoMinerequalized samples were subjected to 2D-DiGE and MS-MALDI-TOF/TOF analyses to identify proteins that were differentially expressed in CD38-/- versus WT mice either with arthritis (Col.II+/CIA+), with no arthritis (Col. II+/CIA-), or with inflmmation (CFA-treated). Altered proteins included those involved in acute phase response (SAA1), inflammation (B2MG, HABP2, Hemoglobin), complement activation (Ficolins, C4-B fragments, C1qb, C3-b-chain), polyclonal B-cell activation (Ig-kappa-light-chain) and lipid metabolism (APOE, APOAI, APOAII, APOAIV, APOJ/Clusterin). Of the proteins that changed in abundance, Hemoglobin and APOE could be indicative of the milder pathological process found in CIA+CD38-/- mice, whereas another set of proteins such as HABP2, Ig-kappa-light-chain, SAA1, Ficolin-1, and Ficolin-2 were clearly associated to the stronger response of WT mice to either collagen immunization or CFA-treatment. Multivariate analyses revealed that the differential protein abundance of 28 distinct protein spots was able to discriminate between CIA+ and CIA- mice, independently of their genetic background. This approach is suitable for the identifi cation of arthritis, or infl ammation serum proteome signatures in mice with distinct genetic backgrounds.