Importantly also, IgG anti-Ro/SSA and anti-La/SSB antibodies have been previously shown to opsonize in-vitro apoptotic cardiocytes and thus to inhibit their clearance by phagocytes. To this end, detailed autoantibody depletion and antigen inhibition experiments are in progress in this laboratory to delineate the characteristics and role of particular antibody specificities in the clearance of apoptotic cells. On the other hand, loss-of-function processes involving the natural IgM immunoglobulins of SS patients may also have a role, as indicated by the occurrence of significantly decreased IgM antiApoCell levels that we observed in the SS patients, compared to healthy individuals. In fact, the important role of natural IgM antibodies for the clearance of apoptotic cells, microbes and various small particles is well-described. In conclusion, this study demonstrates that in a manner similar and comparable to SLE, a significant portion of SS patients is characterized by impaired uptake of early apoptotic cells, as well as of particulate targets by blood-borne phagocytes and macrophages that apparently involves both loss-of-function and gain-of-function processes. Importantly, these aberrations were found to correlate with various clinico-serologic disease indices of SS and SLE, and thus may represent promising areas of search for novel biomarkers for these disorders. The defective clearance of apoptotic cells in SS and SLE appears primarily to depend on serologic aberrations, such as the occurrence of inhibitory IgG anti-ApoCell antibodies and hypocomplementemia, and secondarily on the dysfunction of phagocytes. Such failure of efferocytosis may lead to the accumulation of immunogenic and inflammagenic secondary necrotic cells and debris and the perpetuation thereof of a vicious cycle of inflammatory and autoimmune reactions. In fact, we have recently demonstrated that, SS and SLE patients also manifest impaired serum-mediated degradation of necrotic cell debris that leads to increased amounts of circulating nuclear material and their massive uptake by blood-borne phagocytes. Altogether, these aberrations may represent major causes of the inflammatory and autoimmune reactions that characterize SS and SLE, and may thus hold key roles in the pathogenesis of these disorders. Severe sepsis is the most common cause of death in intensive care units, and its incidence has progressively increased over the past 20 years. Until recently, most clinical trials of new therapeutic approaches for severe sepsis have used 28-day mortality as their primary endpoint. However, it is now increasingly recognised that the sequelae of sepsis extend well beyond the index hospitalisation and that longer-term PCI-32765 outcomes should be used in order to better understand the effect of a given intervention.