S100 are acidic proteins with a molecular weight range of 10-12 KDa that firstly recognized in 1965. They are mostly able to form homodimer and/or heterodimer molecules and considered useful biomarkers for different diseases especially those of inflammatory and autoimmune in nature. The proteins of S100 are mostly coded for by closely linked genes inside a region on the long arm of human chromosome 1 (1q21.3) and have a specific tissue or cell typespecific expression pattern. The S100 proteins can be grouped under the superfamily of EF-hand (a helix-loop-helix structural domain or motif) calciumbinding proteins because they show dual calcium-binding domains; N-terminal S100-specific EF-hand and a C-terminal canonical EF-hand. Diverse intracellular and extracellular functions have been linked to S100 proteins and through which they impact various cellular processes; including, apoptosis, proliferation, migration, energy metabolism, differentiation, calcium ions homeostasis and inflammation. They are also able to interact with various cellular receptors enabling S100 proteins to modulate innate and adaptive immune response with some influence on cell migration and chemotaxis, as well as tissue modeling, growth and repair. Based on these functions, S100 proteins are regarded as alarmins playing significant role in etiology and pathogenesis of juvenile autoimmune and autoinflammatory diseases. A dysregulation of S100 proteins has also been described and represented a prominent factor in pathogenesis and development of various diseases; for instance Alzheimer disease, RA and cancer in general 14. One group of S100 proteins is calgranulins, which comprises A (S100A8), B (S100A9) and C (S100A12) calgranulins.