Détection des anticorps anti-ficoline H chez des patients atteints de lupus érythémateux disséminé

Le lupus érythémateux disséminé (LED) se caractérise par la présence d auto-anticorps dirigés contre les constituants du noyau, cette rupture de tolérance pourrait être due une immunisation contre les antigènes nucléaires provenant de la nécrose des cellules apoptotiques non éliminées. Les ficolines sont des protéines de la voie des lectines du système du complément, outre la reconnaissance des agents pathogènes elles reconnaissent les cellules apoptotiques et participent à leur élimination. La ficoline H a été caractérisée comme étant la cible d auto-anticorps chez un patient atteint de LED. A ce jour, seule une étude ancienne a décrit la présence d anticorps anti-ficoline H dans le sérum de patients lupiques par une technique peu sensible d immun-précipitation. Le but de ce travail a été de mettre au point une technique ELISA pour le dosage des anticorps anti-ficoline H et d évaluer l intérêt de ce dosage chez 43 patients atteints de LED. Nous avons observé que les taux d anticorps anti-ficoline H étaient significativement augmentés chez les patients atteints de LED comparés à ceux des sujets témoins. De plus, ces taux étaient significativement corrélés au SLEDAI. Nous nous sommes ensuite intéressés au suivi de quatre patients atteints de LED, en rémission et en poussée avec atteinte rénale sévère, et nous avons observé une forte association entre des taux élevés d anticorps anti-ficoline H et la phase active de la maladie. En conclusion, le dosage des anticorps anti-ficoline H pourrait avoir un intérêt dans le diagnostic et le suivi du LED. Pour approfondir ces résultats, il est cependant nécessaire d étudier une plus grande population de patients atteints de LED.Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies and accumulation of immune complexes resulting in systemic inflammatory response and tissue damage. Although the underlying mechanisms are complex, defects in dying cells elimination are likely to contribute to autoantigen overload and development of autoimmunity. H-ficolin was initially identified as a serum antigen target for autoantibodies present in SLE patients. Our study aims to investigate the presence of anti-H-ficolin antibodies in a cohort of 43 SLE patients, using a home-made ELISA, to evaluate the clinical significance of anti-H-ficolin antibodies in SLE development and to determine their potential interest as markers for the diagnosis. First, a highly significant difference was found between the anti-H-ficolin levels in SLE patients and those in healthy subjects. Moreover, the titers of anti-H-ficolin antibodies were correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The presence of anti-H-ficolin antibodies was not significantly associated with anti-DNA antibodies and weakly associated with anti-C1q antibodies. Interestingly, the monitoring of four patients sera during acute phase and disease remission showed a strong association of high anti-H-ficolin levels, with active disease characterised by a severe renal involvement. Taken together, these results suggest that anti-ficoline-H antibodies could be of interest for the diagnosis of active lupus forms, but a definitive conclusion requires more extensive investigations.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Association between the Presence of Autoantibodies Targeting Ficolin-3 and Active Nephritis in Patients with Systemic Lupus Erythematosus

International audienceSystemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in the sera of some SLE patients, but their prevalence and significance have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-3 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE. In this retrospective study, sera from SLE patients (n = 165) were selected from a preexisting declared biological collection. Samples from healthy controls (n = 48) were matched with SLE sera. Disease activity was determined according to the SLEDAI score. Anti-ficolin-3, anti-dsDNA and anti-C1q antibodies levels were measured in sera by ELISA. First, a highly significant difference was found in the anti-ficolin-3 levels between SLE patients and healthy subjects. Anti-ficolin-3 antibodies were detected as positive in 56 of 165 (34%) SLE patients. The titer of anti-ficolin-3 antibodies was correlated with the SLEDAI score (r = 0.38, p<0.0001). The presence of anti-ficolin-3 antibodies was associated with anti-C1q and anti-dsDNA antibodies. Regarding associations with clinical manifestations, the presence of active lupus nephritis was significantly associated with the presence of anti-ficolin-3 antibodies (p≤0.001). This association with renal involvement was higher with anti-ficolin-3 or anti-C1q antibodies than with other auto-antibodies. Interestingly, the combination of anti-ficolin-3 and anti-C1q antibodies demonstrated higher specificity than any other serological biomarker. These results suggest that anti-ficolin-3 antibodies could be useful for the diagnosis of active nephritis in SLE patients

Performances of SLE biomarkers.

<p>Performances of SLE biomarkers.</p

Biological characteristics of patients with active and inactive lupus nephritis.

<p>Biological characteristics of patients with active and inactive lupus nephritis.</p

Demographic and clinical variables for SLE patients.

<p>Demographic and clinical variables for SLE patients.</p

Serum anti-ficolin-3 antibodies titers in SLE patients with active disease (flare) or in disease remission.

<p>A) Anti-ficolin-3 titers in SLE patients with active disease (SLEDAI >4) (n = 77) or in disease remission (SLEDAI ≤4) (n = 88). B) Anti-ficolin-3 titers in SLE patients with active disease with renal involvement (n = 36) or without renal involvement (n = 41). Horizontal lines in each group indicate the median values. Statistical analyses were performed by Mann-Whitney test.</p

Characteristics of SLE patients with lupus nephritis.

<p>Characteristics of SLE patients with lupus nephritis.</p

Detection of anti-ficolin-3 antibodies in patients with SLE.

<p>A) Binding of anti-ficolin-3 antibodies to immobilized ficolin-3. Microtiter plates were coated with ficolin-3. Sera from SLE patients and healthy controls were added in serial dilutions. Results represent the mean +/- standard deviation. B) Anti-ficolin-3 antibodies in serum samples. Anti-ficolin-3 antibodies were measured in 48 samples from healthy controls and in 165 samples from patients with SLE. Horizontal lines in each group indicate the median values. Statistical analyses were performed by Mann-Whitney test. A, absorbance; AU, Arbitrary units.</p

Association between anti-ficolin-3 antibodies titers, biological markers and disease activity in patients with SLE.

<p>Association between anti-ficolin-3 titers and anti-dsDNA antibodies (A), anti-C1q antibodies (B) and ficolin-3 concentrations (C) in SLE. D) Association between anti-ficolin-3 titers and SLE Disease Activity Index (SLEDAI). Statistical analyses were performed by Spearman’s rank correlation test.</p