Reduced expression of CD44 on monocytes and neutrophils in systemic lupus erythematosus: relations with apoptotic neutrophils and disease activity

Abstract

Background-Increased numbers of apoptotic neutrophils, and impaired monocyte/macrophage clearance of apoptotic cells, have been demonstrated in systemic lupus erythematosus (SLE). CD44 is implicated in the clearance of apoptotic neutrophils. Objective-To determine the expression of CD44 on peripheral blood monocytes and neutrophils in SLE, and examine the relations with disease activity and numbers of circulating apoptotic neutrophils. Methods-Peripheral blood was sampled from 31 patients with SLE, 19 healthy normal subjects, and 19 patients with rheumatoid arthritis (RA). Monocyte and neutrophil density of surface CD44 expression was determined by immunofluorescence labelling and flow cytometry, and results expressed as mean channel fluorescence (MCF) values. Neutrophil apoptosis was measured by morphology in 15 patients with SLE, nine with RA, and six normal subjects. Results-Monocyte CD44 expression was significantly lower in SLE (median MCF 4.71) than in healthy normal subjects (median MCF 5.61) and controls with RA (median MCF 5.39). Neutrophil CD44 expression was also significantly lower in SLE (median MCF 1.95) than in healthy normal subjects (median MCF 2.37) and controls with RA (median MCF 2.60). Monocyte, but not neutrophil, CD44 expression correlated negatively with the percentage of apoptotic neutrophils. There was no significant correlation of monocyte or neutrophil CD44 expression in SLE with disease activity or damage. Conclusions-Monocyte and neutrophil CD44 expression is reduced in SLE, and this may contribute to the impaired recognition and clearance of apoptotic neutrophils by monocyte derived macrophages. (Ann Rheum Dis 2001;60:950-955) Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which tissue damage can best be explained by the production of pathogenic autoantibodies and their participation in immune complex formation. The description of nuclear autoantigen expression (including Ro, La, and dsDNA) on cytoplasmic blebs of apoptotic cells provides an attractive explanation for the unique clustering of autoantibodies in SLE.

Self-dsDNA in the pathogenesis of systemic lupus erythematosus

“…Macrophages from SLE patients cultured in vitro are smaller, with impaired adhesion and decreased phagocytic capacity for autologous apoptotic material [28,29]. More direct evidence of the involvement of clearance deficiency in the aetiology of SLE comes from lymph node biopsy.…”

The −844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE

“…Furthermore, altered monocyte phenotypes and neutropenia lead to impaired recognition and clearance of apoptotic cells, and correlate with anti-dsDNA and disease activity. 6,[9][10][11] Fas ligand (FasL), a trimeric type II membrane protein, belongs to the TNF receptor family that induces apoptosis of cells bearing Fas receptor. 12 Observations in mouse models of SLE demonstrated that mice with Fas (MRL/lpr) or FasL (gld) mutations developed lymphadenopathy with accumulation of CD4ÀCD8À double negative lymphocytes.…”

Differential Immuno-Reactivity to Genomic DNA, RNA and Mitochondrial DNA is Associated with Auto-Immunity

“…However, during SLE, clearance of genetic material is delayed leading to subsequent accumulation of apoptotic cell debris, which can provoke inflammatory response and breakdown of self-tolerance [21,22]. Impaired clearance of neutrophil extracellular traps (NETs) has been described in SLE cases as well [23]. It has been suggested that reduced degradation of NETs is associated with decreased DNAse I activity which is often observed in SLE [24].…”