Hydroxychloroquine modulates elevated expression of S100 proteins in systemic lupus erythematosus

Abstract

Objectives We investigated the effect of hydroxychloroquine (HCQ) on S100A8 and S100A9 serum levels in systemic lupus erythematosus (SLE) patients with low disease activity receiving immunosuppressants. Methods SELENA-SLEDAI, Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum levels of complement factors, anti-dsDNA antibodies, and white blood cell, lymphocyte, and platelet counts were used to evaluate disease activity, cutaneous disease activity, and immunological activity, respectively. Serum S100A8 and S100A9 were measured at HCQ administration and after 3 or 6 months using ELISA. Results S100A8 and S100A9 serum levels were elevated at baseline and the magnitude of decrease from baseline at 3 and 6 months after HCQ administration was greater in patients with renal involvement than in those without (baseline: S100A8, p = 0.034; S100A9, p = 0.0084; decrease: S100A8, p = 0.049; S100A9, p = 0.023). S100 modulation was observed in patients with ( n = 17; S100A8, p = 0.0011; S100A9, p = 0.0002) and without renal involvement ( n = 20; S100A8, p = 0.0056; S100A9, p = 0.0012), and was more apparent in patients with improved CLASI activity scores (improved: S100A8, p = 0.013; S100A9, p = 0.0032; unimproved: S100A8, p = 0.055; S100A9, p = 0.055). No associations were observed for immunological biomarkers. Conclusion HCQ may improve organ involvement in SLE by modulating S100 protein levels, especially in patients with renal or skin involvement.

Effect of Add-on Hydroxychloroquine Therapy on Serum Proinflammatory Factor Levels in Patients with Systemic Lupus Erythematosus With or Without Lupus Nephritis

“…We previously reported that HCQ modulates serum levels of S100A8 and S100A9 in SLE patients with LDA [21]. S100 proteins are components of neutrophil extracellular traps (NETs), which play an important role in the pathogenesis of SLE [39] [40].…”

“…Willis et al showed that HCQ therapy resulted in signi cant clinical improvement in a manner that strongly correlated with reductions in IFN-α levels [20]. Our previous study suggested that HCQ modulated the expression of S100 proteins in SLE patients with LDA [21]. However, little is known about the effects of HCQ on biomarkers in SLE patients with LDA.…”

The pathogenesis of cutaneous lupus erythematosus: The aberrant distribution and function of different cell types in skin lesions

“…Recently, HCQ is reported to significantly inhibit S100 proteins and S100 proteins which are ligands for TLR4 are related to organ involvement in SLE. HCQ reduces S100 proteins and then results in inhibition of TLR4 signalling, which may indicate the mechanism of skin lesion alleviation in SLE patients 113 . Also, in a more recently case reported HCQ treatment in a 34‐year‐old woman with DLE, and after 5 months of HCQ administration at a dose of 200 mg/day without prednisolone (PSL) dosage increased, the skin lesions completely resolved 114 .…”

“…HCQ reduces S100 proteins and then results in inhibition of TLR4 signalling, which may indicate the mechanism of skin lesion alleviation in SLE patients. 113 Also, in a more recently case reported HCQ treatment in a 34-year-old woman with DLE, and after 5 months of HCQ administration at a dose of 200 mg/day without prednisolone (PSL) dosage increased, the skin lesions completely resolved. 114 Topical corticosteroids are the first-line topical therapy for skin lesions in CLE, while corticosteroids can result in skin atrophy in CLE treatment.…”

New insights in gut-liver axis in wild-type murine imiquimod-induced lupus

“…Calprotectin is a calcium-binding protein found in neutrophilic granulocytes; because it resists metabolic degradation and can be measured in feces with ease, fecal calprotectin is a reliable marker of inflammation or damage in the gastrointestinal tract. 14 Although fecal calprotectin has been classically associated with increased intestinal permeability and gut immune activation in inflammatory bowel diseases, 15 and serum calprotectin correlated to lupus activity, 16 its relation to intestinal permeability has been scantly investigated in lupus. 17…”