Background Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by production of autoantibodies. The anti-double stranded DNA (anti-dsDNA) autoantibodies are diagnostic biomarkers of SLE. A subset of anti-dsDNA antibodies can enter living cells and induce cytokine secretion. Our previous studies have reported that internalizable anti-DNA IgG localize to the cytosol and trigger secretion of IL-8 and TNF-a in primary human CD14+ monocytes. In this study, we detected the presence of antibodies that localized to the cytosol in monocytes obtained from the patients with SLE.
Methods Cytosolic localization of IgG in CD14+ monocyte gated from PBMC of healthy controls (n=65) and SLE patients (n=160) was analyzed using a FACSCanto II flow cytometer. The Alexa Fluor 488 fluorescence intensity resulting from Igs existence (κ and λ chain of Ig) within the CD14+ monocyte population was then quantified as the mean fluorescence intensity (MFI). The presence of cytosolic IgG was determined by the ratio of permeabilization (P) to non-permeabilization (NP). [formula: Ratio of P:NP = (P – Control P)/(NP – Control NP)]
Results We show a statistically significant association between cytosolic localization of antibodies (ratio of P:NP) and disease activity in the patients with SLE. Compared with healthy controls (MFI=1.082), SLE patients had higher levels in active (MFI=1.245) and inactive (MFI=1.328) disease.
Conclusions Antibodies in the patients with SLE highly localize to the cytosol of monocytes, depending on the disease activity defined by SLE disease activity index (SLEDAI).
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