Collagen type II-induced arthritis (CIA) is an autoimmune disease that is accompanied by a complex host systemic response, which includes inflammatory and autoimmune reactions. Since to develop CIA is required the injection of antigen in complete Freund’s adjuvant (CFA), which is a water-in-mineral-oil emulsion containing killed Mycobacteria, systemic response proteins related with inflammation can confound the detection or diagnosis of arthritis. CIA in CD38 deficient mice (CD38 KO) is milder than that in C57BL/6 (B6 WT) mice. Protein extracts from spleen were subjected to 2D-DiGE and MS-MALDI-TOF/TOF analysis to identify proteins that were differentially expressed in CD38 KO and B6 WT mice with arthritis, with inflammation, or non-immunized. Differential protein expression was validated by ELISA, or Western-blotting.