S100 proteins in rheumatic diseases

Rheumatic diseases are characterized by sterile inflammation that causes severe long-term damage to various organ systems. A growing body of evidence supports a pivotal role for the pro-inflammatory calcium-binding S100 family of proteins in the pathogenesis of rheumatic diseases. Some S100 proteins are released at the site of inflammation and act as danger-associated molecular pattern molecules by activating pattern recognition receptors. Increased concentrations of S100 proteins in serum and synovial fluid closely correlate with disease activity in several rheumatic diseases and serve as useful biomarkers for monitoring disease activity. Some S100 proteins are also valid biomarkers for predicting response to treatment, systemic organ involvement or disease flares in rheumatic diseases. Analyses of knockout mouse models have confirmed a functional role for S100 proteins, particularly S100A8 and S100A9, in rheumatic diseases, indicating that blocking the expression, release or function of these proteins might be an innovative therapeutic strategy. Owing to their local pattern of expression, specific mechanism of release and autoregulatory effects, such therapeutic approaches would primarily target the local inflammatory process and present only minor risks of systemic adverse effects.