Association of Anti–Acidic Ribosomal Protein P0 and Anti–Galectin 3 Antibodies With the Development of Skin Lesions in Systemic Lupus Erythematosus

Abstract

Objective. The specific autoantibodies and antigens that mediate systemic lupus erythematosus (SLE)-related organ injuries remain largely unknown. This study was undertaken to investigate the antibodymediated immune response that leads to SLE skin lesions.Methods. The study included 85 SLE patients with lupus-specific skin lesions and 31 without skin lesions. The reactivity of serum antibody with skin antigens was determined by immunoblotting using human foreskin as the substrate. Skin antigens were identified using mass spectrometry. Serum antibody was isolated by affinity purification and was injected intracutaneously into mouse skin to determine pathogenicity. Serum antibody levels were monitored by enzyme-linked immunosorbent assay.Results. We determined that 78% of the patients with skin lesions had serum antibodies reactive with 35-kd and/or 25-kd skin antigens, which was significantly higher than the percentage of patients without skin lesions (P < 0.0001), suggesting a correlation between immune response and skin lesions. Acidic ribosomal protein P0 (RPLP0) and galectin 3 were 2 target antigens identified from 35-kd and 25-kd proteins, respectively. Purified serum anti-RPLP0 and anti-galectin 3 antibodies induced lupus-like histologic changes after intracutaneous injection. Anti-RPLP0 and anti-galectin 3 antibody levels were significantly higher in SLE patients than in healthy controls and decreased with skin recovery. Anti-galectin 3 antibody levels were not significantly higher in SLE patients than in patients with dermatomyositis or scleroderma, but strongly related to lupus cutaneous vasculitis. Additionally, levels of the 2 antibodies were positively correlated with leukopenia and C3 deficiency, and the anti-RPLP0 antibody level was also positively correlated with arthritis and SLE disease activity. Conclusion. Our findings indicate that the immune response mediated by serum anti-RPLP0 and anti-galectin 3 antibodies plays a key role in the pathogenesis of SLE skin lesions. These findings provide new insights into the mechanism of SLE-related organ disorders.Systemic lupus erythematosus (SLE) is a unique autoimmune disease characterized by extremely heterogeneous clinical manifestations and the most complex autoantibody profile (1-5). Autoantibodies not only serve as a marker of disease diagnosis, activity, and severity (6,7), but they also play a primary and pivotal role in the initiation and exacerbation of SLE disease (8,9). A cluster of anti-nuclear debris antibodies, including anti-double-stranded DNA (anti-dsDNA), anti-

Plasma galectin‐3 levels do not differ in systemic lupus erythematosus patients

“…Shi et al found that anti‐galectin‐3 antibody of SLE patients was significantly higher as compared to healthy individuals. Additionally, anti‐galectin‐3 antibody decreased with skin recovery and was strongly related to lupus cutaneous vasculitis . It identified the mechanism of SLE skin damage and demonstrated that interaction of tissue antigens with specific antibodies contributes to SLE organ damage.…”

“…Additionally, anti-galectin-3 antibody decreased with skin recovery and was strongly related to lupus cutaneous vasculitis. 10 It identified the mechanism of SLE skin damage and demonstrated that interaction of tissue antigens with specific antibodies contributes to SLE organ damage. Kang et al showed that serum levels of galectin-3 were elevated in SLE, particularly in those with nephritis, when compared with healthy subjects.…”

“…Moreover, 2 studies showed that galectin‐3 may be correlated with complement 3 and 4 levels and anti‐double‐stranded DNA (anti‐dsDNA) in SLE . In addition, a recent study showed that the pathogenesis of SLE‐related skin injuries may be closely related to anti‐galectin‐3 antibodies, but evidence of the association between clinical manifestations of SLE and galectin‐3 remains limited.…”

Pathogenesis and targeted treatment of skin injury in SLE

“…59,60 Antibodies against 60S acidic ribosomal protein P0 (RPLP0) and galectin 3 are related to the development of skin lesions in SLE. 61 Anti-Ro antibodies have been associated with skin lesions and photo sensitivity, 4 and have been found deposited in the skin of patients with SLE. Ro52 (also known as E3 ubiquitin-protein ligase TRIM21) is a common target of autoantibodies in SLE, and Ro52 is expressed at high levels in the skin of patients with spontan eous CLE and UV-induced inflammatory lesions; indeed, approximately 80% of infiltrating cells within CLE lesions stain positive for Ro52.…”

Selected novel aspects in pathogenesis of lupus erythematosus – interdisciplinary view

“…Stwierdzono, że hodowle keratynocytów, które nie produkują Gal-3, są bardziej wrażliwe na apoptozę indukowaną przez promieniowanie ultrafioletowe. W 2015 roku ukazała się praca, w której wykazano, że przeciwciała anty-Gal-3 mogą odgrywać istotną rolę w toczniu [33]. Badania przeprowadzono u 85 pacjentów z SLE ze zmianami skórnymi oraz u 31 pacjentów z SLE bez zmian skórnych.…”