The degree of inflammation in auto-immune diseases such as rheumatoid arthritis is often assessed in serum and used for diagnostic and prognostic purposes. The serum levels of acute inflammatory signaling molecules (C-reactive protein and serum amyloid A) in conjunction with the important pro-inflammatory cytokines themselves may have limited utility due to several limitations. (1) These traditional biomarkers are associated with substantial variation due to biological not technical issues. (2) The combined burden of cytokines rather than one single player may be responsible for the progression of disease. (3) The cellular and tissue origins of cytokines that are detected systemically are difficult to determine as the cytokines lack tissue specificity. (4) There is substantial redundancy in the signaling potential of cytokines. Despite these major limitations, the total burden of inflammatory signaling molecules and pro-inflammatory cytokines are important in assessing the degree of inflammation in conjunction with a diagnosis of disease. The total burden of signaling ultimately results in protease expression, tissue destruction and disease progression. One of the pivotal events in the downstream inflammatory signaling is the generation of pathological enzymes, which results in the release of small but tissue-specific protein fragments into the serum that may be used as molecular biochemical markers. We discuss the potential of this new class of biochemical markers, which may be viewed as "end products of tissue destruction". These so-called protein fingerprints may also be considered end-products of the convergence cytokine signaling pathways, as they are the final end-result of tissue destruction.