Immune memory and activation markers in systemic lupus erythematosus

Master'sMASTER OF SCIENC

Lipid anti-lipid antibody responses correlate with disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by broad clinical manifestations including cardiovascular and renal complications with periodic disease flares and significant morbidity and mortality. One of the main contributing factors to the pathology of SLE is the accumulation and impaired clearance of immune complexes of which the principle components are host auto-antigens and antibodies. The contribution of host lipids to the formation of these autoimmune complexes remains poorly defined. The aim of the present study was to identify and analyze candidate lipid autoantigens and their corresponding anti-lipid antibody responses in a well-defined SLE patient cohort using a combination of immunological and biophysical techniques. Disease monitoring in the SLE cohort was undertaken with serial British Isles Lupus Assessment Group (BILAG) scoring. Correlations between specific lipid/anti-lipid responses were investigated as disease activity developed from active flares to quiescent during a follow up period. We report a significant negative correlation between anti-lipid antibodies for 24S-hydroxycholesterol, cardiolipin and phosphatidylserine with SLE disease activity. Taken together, these data suggest that lipid autoantigens represent a new family of biomarkers that can be employed to monitor disease activity plus the efficacy of therapeutic intervention in SLE

Lipid anti-lipid antibody responses correlate with disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by broad clinical manifestations including cardiovascular and renal complications with periodic disease flares and significant morbidity and mortality. One of the main contributing factors to the pathology of SLE is the accumulation and impaired clearance of immune complexes of which the principle components are host auto-antigens and antibodies. The contribution of host lipids to the formation of these autoimmune complexes remains poorly defined. The aim of the present study was to identify and analyze candidate lipid autoantigens and their corresponding anti-lipid antibody responses in a well-defined SLE patient cohort using a combination of immunological and biophysical techniques. Disease monitoring in the SLE cohort was undertaken with serial British Isles Lupus Assessment Group (BILAG) scoring. Correlations between specific lipid/anti-lipid responses were investigated as disease activity developed from active flares to quiescent during a follow up period. We report a significant negative correlation between anti-lipid antibodies for 24S-hydroxycholesterol, cardiolipin and phosphatidylserine with SLE disease activity. Taken together, these data suggest that lipid autoantigens represent a new family of biomarkers that can be employed to monitor disease activity plus the efficacy of therapeutic intervention in SLE

Levels of unsaturated fatty acids and anti-unsaturated fatty acids IgG in SLE patients’ plasma.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055639#pone-0055639-g003" target="_blank">Figure 3ai and 3ai</a>i. Phosphatidylserine levels and anti-phosphatidylserine IgG levels in plasma. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055639#pone-0055639-g003" target="_blank">Figure 3bi and 3bii</a>. Isoprostane (15-F_2t-IsoP +5-F_2t-IsoP) levels normalized against AA values and anti-15-F_2t-IsoP IgG levels in plasma. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055639#pone-0055639-g003" target="_blank">Figure 3ci</a>. Isoprostane (8-F_2t-IsoP) levels normalized against AA values. p<0.05 value was considered as significant in Wilcoxon test.</p

Levels of oxysterol and anti-oxysterol IgG in SLE patients’ plasma.

<p>Analysis by GC<i>-</i>MS and ELISA show higher levels of oxidized cholesterols or anti-cholesterol IgGs in patients during flare versus follow-up period. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055639#pone-0055639-g002" target="_blank">Figure 2ai and 2 aii</a>. 7-α-hydroxycholesterol levels and anti-7-α-hydroxycholesterol IgG levels in plasma. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055639#pone-0055639-g002" target="_blank">Figure 2bi and 2bii</a>. 7-β-hydroxycholesterol levels and anti-7-β-hydroxycholesterol IgG levels in plasma. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055639#pone-0055639-g002" target="_blank">Figure 2ci and 2cii</a>. 7-ketocholesterol levels and anti-7-ketocholesterol IgG levels in plasma. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055639#pone-0055639-g002" target="_blank">Figure 2di and 2dii</a>. 24S-hydroxycholesterol levels and anti-24S-hydroxycholesterol IgG levels in plasma. p<0.05 value was considered as significant in Wilcoxon test.</p

SLE disease activity score measured with the BILAG index reduces significantly over the time while total IgG levels remain the same.

<p>The British Isles Lupus Assessment Group (BILAG) index score during disease flare and the follow-up period. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055639#pone-0055639-g001" target="_blank">Figure 1a</a>. A significant improvement is detectable over the time. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055639#pone-0055639-g001" target="_blank">Figure 1b</a>. A level of total IgGs in patients’ blood is similar during disease flares and in the follow-up period. p<0.05 value considered significant in Wilcoxon test.</p

A summary of reported lipids and anti-lipid antibodies involved in autoimmune, degenerative and age-related diseases.

<p>A summary of reported lipids and anti-lipid antibodies involved in autoimmune, degenerative and age-related diseases.</p

Biomarker candidates that correlate with BILAG scores.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055639#pone-0055639-g005" target="_blank">Figure 5ai, 5bi, 5ci</a>. Anti-24S hydroxycholesterol IgG, anti-cardiolipin IgG and anti-phosphatidylserine IgG levels negatively correlate with BILAG scores. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055639#pone-0055639-g005" target="_blank">Figure 5bii</a>. Anti-7-α-hydroxycholesterol IgG levels also show trend of negative correlation with BILAG scores. p<0.05 value was considered as significant in Spearman correlation and Linear regression tests.</p