Plasma levels of high-mobility group box 1 and soluble receptor for advanced glycation end products in primary antiphospholipid antibody syndrome patients

<div><p>Introduction</p><p>Many studies have demonstrated elevated circulating levels of high-mobility group box 1 (HMGB1) and decreased circulating levels of soluble receptor for advanced glycation end products (sRAGE) in patients with autoimmune diseases. In the present study, we investigated plasma levels of both HMGB1 and sRAGE in primary antiphospholipid syndrome (pAPS) patients.</p><p>Methods</p><p>We prospectively recruited 11 pAPS patients, 17 antiphospholipid antibody (APA)-positive SLE patients without APS manifestations (APA⁺SLE) and 12 SLE patients with secondary APS (APS⁺SLE). We also recruited 10 healthy controls (HCs). Plasma levels of HMGB1 and sRAGE were determined using sandwich ELISA kits. In addition, plasma levels of HMGB1 were also determined using Western blot in 6 pAPS patients and 6 HCs.</p><p>Results</p><p>There was no significant difference in plasma levels of HMGB1 measured by ELISA among subgroups of the enrolled subjects. In addition, there was no significant difference in plasma levels of HMGB1 measured by Western blot between pAPS patients and HCs. On the other hand, we observed a trend toward lower plasma levels of sRAGE in APA⁺SLE or APS⁺SLE patients when compared with HCs. However, there was no significant difference in plasma levels of sRAGE between pAPS patients and HCs, or between APA⁺SLE patients and APS⁺SLE patients.</p><p>Conclusion</p><p>There was no significant difference in plasma levels of sRAGE or HMGB1 between pAPS patients and HCs. Plasma levels of sRAGE/HMGB1 could not be utilized to differentiate between APA⁺SLE and APS⁺SLE patients.</p></div

Baseline characteristics of the enrolled subjects.

<p>Baseline characteristics of the enrolled subjects.</p

Comparisons of plasma levels of HMGB1 and sRAGE measured by ELISA between subgroups of the enrolled patients and HCs.

<p>(a) Comparison of plasma levels of HMGB1 between pAPS, APA⁺SLE, APS⁺SLE patients and HCs. (b) Comparison of plasma levels of HMGB1 between SLE patients with and without disease flares. (c) Comparison of plasma levels of sRAGE between pAPS, APA⁺SLE, APS⁺SLE patients and HCs. (d) Comparison of plasma levels of sRAGE between SLE patients with and without disease flares. P values of < 0.008 were regarded as statistically significant for multiple comparisons. APA, antiphospholipid antibody; HC, healthy control; HMGB1, high-mobility group box 1; pAPS, primary antiphospholipid syndrome; SLE, systemic lupus erythematosus; sRAGE, soluble receptor for advanced glycation end products.</p

Correlation analyses between plasma levels of sRAGE, HMGB1 and serum ACA IgG or IgM titers among the enrolled patients.

<p>(a) Correlation between plasma levels of HMGB1 and serum ACA IgG titers; (b) Correlation between plasma levels of sRAGE and serum ACA IgG titers; (c) Correlation between plasma levels of HMGB1 and serum ACA IgM titers; (d) Correlation between plasma levels of sRAGE and serum ACA IgM titers. Correlation analyses were performed using Spearman’s rank correlation test. ACA: anticardiolipin antibodies; HMGB1, high-mobility group box 1; sRAGE, soluble receptor for advanced glycation end products.</p

Correlation analyses between plasma levels of sRAGE, HMGB1, serological markers of disease activity and SLEDAI among SLE patients.

<p>(a) Correlation between plasma levels of HMGB1 and sRAGE; (b) Correlation between plasma levels of HMGB1 and serum anti-dsDNA; (c) Correlation between plasma levels of HMGB1 and serum C3; (d) Correlation between plasma levels of HMGB1 and serum C4; (e) Correlation between plasma levels of HMGB1 and SLEDAI; (f) Correlation between plasma levels of sRAGE and serum anti-dsDNA; (g) Correlation between plasma levels of sRAGE and serum C3; (h) Correlation between plasma levels of sRAGE and serum C4; (i) Correlation between plasma levels of sRAGE and SLEDAI. Correlation analyses were performed using Spearman’s rank correlation test. ^aOne APS⁺SLE patient did not receive anti-dsDNA, C3 and C4 examinations. APS, antiphospholipid syndrome; C3, complement 3; C4, complement 4; anti-dsDNA, anti-double-stranded DNA antibody; HMGB1, high-mobility group box 1; SLE, systemic lupus erythemtosus; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index; sRAGE, soluble receptor for advanced glycation end products.</p

The relationships between subgroups of patients and log-transformed plasma levels of HMGB1 or sRAGE in a multivariate linear regression model (R² = 0.04 for plasma HMGB1; R² = 0.19 for plasma sRAGE).

<p>The relationships between subgroups of patients and log-transformed plasma levels of HMGB1 or sRAGE in a multivariate linear regression model (R² = 0.04 for plasma HMGB1; R² = 0.19 for plasma sRAGE).</p

Comparisons of plasma levels of HMGB1 measured by Western blot between pAPS patients and HCs.

<p>(a) Poor correlation of ELISA with Western blot in the measurement of plasma levels of HMGB1 in both pAPS patients and HCs. (b) Comparison of plasma levels of HMGB1 between pAPS patients and HCs. Band intensities were quantified by ImageJ. HC, healthy control; HMGB1, high-mobility group box 1; pAPS, primary antiphospholipid syndrome; WB, Western blot.</p