Les marqueurs biologiques du lupus érythémateux disséminé, intérêt des anticorps anti-ficoline H

Le lupus érythémateux disséminé est une connectivite fréquente. Les marqueurs biologiques actuels, notamment les anticorps anti-ADN et les anticorps anti-C1q, sont insuffisants pour le suivi de cette pathologie en particulier en cas d atteinte rénale. Les anticorps anti-ADN, marqueur le plus utilisé, sont très variables selon les techniques de dosage. La ficoline H est une protéine de reconnaissance de la voie des lectines du complément ; elle a un faible rôle anti-infectieux mis en évidence et par contre un rôle puissant d opsonisation des cellules apoptotiques. La ficoline H a été initialement identifiée comme un antigène cible d auto-anticorps chez des patients lupiques. L objectif principal de cette étude a donc été d évaluer l intérêt des anticorps anti-ficoline H, parmi les autres marqueurs biologiques, chez 136 patients lupiques. Notre étude a montré que les anticorps anti-ficoline H sont présents de façon significative chez les patients lupiques par rapport aux sujets sains. Elle a aussi montré que ces anticorps sont associés à l activité lupique : corrélation avec le SLEDAI ( Systemic lupus erythematosus disease activity index ) (50 patients en poussée, 86 patients en rémission). Chez ces patients en poussée les anticorps anti-ficoline H sont associés à l atteinte rénale et non aux autres types d atteintes. Ces résultats sont confirmés dans le suivi de 11 patients. En conclusion, le dosage des anticorps anti-ficoline H semble utile au diagnostic et au suivi, en particulier rénal, des patients lupiques.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

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

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

Characteristics of SLE patients with lupus nephritis.

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

Performances of SLE biomarkers.

<p>Performances of SLE biomarkers.</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