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.

Figure 1

(A) Flow cytometry scatter plot demonstrating the three leucocyte populations—from left to right: lymphocytes, monocytes (gated), and neutrophils; (B) gated monocyte IgG isotype control histogram; (C) gated monocyte CD44 staining histogram—in this sample 99.3% of gated cells express CD44 with a mean channel fluorescence of 6.74.

Figure 2

Monocyte CD44 expression in normal subjects, patients with systemic lupus erythematosus (SLE), and patients with rheumatoid arthritis (RA). Each point represents one patient, and the median value for each group is shown.

Figure 3

Neutrophil CD44 expression in normal subjects, patients with systemic lupus erythematosus (SLE), and patients with rheumatoid arthritis (RA). Each point represents one patient, and the median value for each group is shown.

Figure 4

Scatter plot showing the negative correlation of monocyte CD44 expression with percentage apoptotic neutrophils (r_s=−0.41, p=0.026). Data from patients with systemic lupus erythematosus (SLE), patients with rheumatoid arthritis (RA), and normal subjects are included, and each point represents one patient. MCF = mean channel fluorescence.