Normally, cells dying by apoptosis undergo specific changes that target them for rapid clearance by professional phagocytes, such as macrophages. This process leads to the active production of anti-inflammatory mediators by phagocytes and thus facilitates the “immunologically silent” removal of GANT61 molecular weight apoptotic cells. The prompt elimination of apoptotic cells is a very crucial biological process, since lingering apoptotic cells eventually proceed to the state of “late apoptosis” or “secondary necrosis” wherein they may contribute to inflammatory reactions via the release of immunogenic intracellular components, including modified autoantigens and “danger signals”. In fact, apoptosis and efferocytosis act in concert to regulate various processes, such as embryogenesis, tissue homeostasis, tolerance the elimination of damaged cells, and the resolution of inflammation. The occurrence of defective efferocytosis in certain inflammatory diseases is thought to have pathogenetic significance, based on the pro-inflammatory potential of secondary necrotic cells Among them, systemic lupus erythematosus is regarded as the archetypical disease model where the impaired clearance of apoptotic cells by macrophages represents a possible mechanism for the development of chronic autoimmune reactions and organ damage. Apart from defective efferocytosis, various in vitro clearance defects of macrophages have been described in SLE, including aberrant Fc-gamma receptor-mediated uptake of IgG ligand-coated erythrocytes and decreased phagocytosis of yeast cells and particulate targets. These aberrations have been attributed to intrinsic defects of patients’ phagocytes, to the decreased density of circulating macrophages, as well as to the effect of serum components. Primary Sjo¨gren’s syndrome, which is characterized by mononuclear cell infiltrates in exocrine glands and parenchymal organs, shares several immunologic manifestations with SLE. These include various features of B-cell hyperactivity, such as the profound hypergammaglobulinemia, multiple autoantibodies, circulating immune complexes and evidence of complement consumption. In this context, we presently sought to comparatively investigate the capacity of peripheral blood monocytes and monocyte-derived macrophages of SS and SLE patients for phagocytosis of apoptotic cells and of particulate targets. For this purpose, we established ex-vivo phagocytosis assays and assessed patients with SLE, SS and RA, as well as healthy individuals. Our findings indicate that considerable proportions of SS and SLE patients manifest deficient phagocytosis of apoptotic cells and of particulate targets that correlate with the activity of these diseases, and apparently owes primarily to inhibitory IgG anti-ApoCell antibodies and secondarily to the dysfunction of phagocytes. Several previous studies had documented that the monocytes of SLE patients manifest reduced clearance of various targets, including defective efferocytosis.