Objective Decreased clearance of apoptotic cells is suggested to be a major pathogenic factor in systemic lupus erythematosus (SLE). The aim of this study was to investigate whether the binding of SLE autoantibodies to apoptotic cells influences the phagocytosis of these cells by macrophages. Methods Apoptosis was induced in a human T cell line (Jurkat) and a keratinocyte cell line (HaCaT) by ultraviolet B irradiation. Binding of purified IgG from 26 SLE patients and 15 healthy controls to apoptotic cells was assessed by flow cytometry and Western blotting. Phagocytosis of IgG‐opsonized apoptotic cells by monocyte‐derived macrophages was assessed by light microscopy. Similar experiments were performed with a monoclonal antibody against SSA/Ro and IgG fractions from 5 patients with Sjögren's syndrome (SS) and 5 patients with rheumatoid arthritis (RA). Results IgG fractions from all 26 SLE patients bound to late apoptotic, but not early apoptotic, cells. IgG fractions isolated from SLE patients with different autoantibody profiles showed comparable levels of binding. IgG fractions from healthy controls did not bind. Opsonization of apoptotic cells with IgG fractions from SLE patients resulted in a significant inhibition of phagocytosis as compared with healthy control IgG fractions. A monoclonal antibody directed against SSA/Ro and IgG isolated from 5 antinuclear antibody (ANA)–positive patients with SS were also able to elicit these effects, whereas IgG from 5 ANA‐negative patients with RA did not. The inhibitory effect of patient IgG was abolished by blocking either the Fcγ receptors (FcγR) or the constant region of IgG, using a specific Fc‐blocking peptide. Conclusion Autoantibodies from SLE patients are able to opsonize apoptotic cells and inhibit their uptake by macrophages via an FcγR‐dependent mechanism.
The objective of this study was to establish the relationship between Candida vaginalis and (pre)neoplasia and the prevalence of Candida and (pre)neoplasia related to age and ethnicity. Data were collected from 445,671 asymptomatic women invited for mass screening between 1995 and 2002 and coded according to the Dutch cervical smear coding system (KOPAC) with six grades for (pre)neoplastic changes. Prevalence and relative risks (RRs) were established for Candida and squamous abnormalities in Dutch women and four groups of immigrants. The prevalence of Candida is significantly higher in the cohort of 30-year-old women and lower in the cohorts of 45-, 50-, 55-, and 60-year-old women. The RR of having Candida was higher for Surinamese women (1.24; CI 1.08-1.42). Furthermore, the RR of having mild dysplasia was higher for Surinamese women (1.47; CI 1.14-1.89) and for women born in other countries than in The Netherlands, Turkey, and Morocco (1.36; CI 1.13-1.62). No statistically significant relationship between (pre)neoplasia and Candida was observed. C. vaginalis is more frequent among Surinamese women. Presence of Candida is not associated with an increased risk for squamous abnormalities; therefore, women carrying Candida are not at an increased risk of developing cervical cancer.
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