Anti-annexin II Antibodies in Systemic Autoimmune Diseases and Antiphospholipid Syndrome

Salle, V.; Mazière, J.C.; Смаил, А.; Cévallos, R.; Mazière, Cécile; Fuentes, Vincent; Tramier, B.; Makdassi, R; Choukroun, Gabriel; Vittecoq, Olivier; Goëb, Vincent; Ducroix, J.P.

doi:10.1007/s10875-008-9188-1

Cited by 69 publications

(65 citation statements)

References 27 publications

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“…Actually, other studies reported an association of antiannexin antibodies with peculiar autoimmune conditions, such as discoid lupus 25 and antiphospholipid syndrome, typically a serious condition potentially causing vascular events. [26][27][28] Therefore, our results go in the direction of other reports that already suggested a generic implication of antihistones, anti-DNA, and antipodocyte antibodies. 11,29,30 Looking at the renal composition of autoantibodies, a relevant finding here is the preponderance in glomeruli of antibodies of the IgG2 isotype (anti-a-enolase/annexin AI and H3 histone) with little amounts of anti-DNA IgG3 and predominant colocalization of anti-IgG4 with C1q in subepithelial deposits of class V biopsies.…”

Section: Discussionsupporting

confidence: 89%

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2)

Bruschi¹,

Galetti

Sinico

et al. 2015

Journal of the American Society of Nephrology

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Glomerular planted antigens (histones, DNA, and C1q) are potential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patients with LN. Prevalent antibody isotypes were defined, levels were determined, and glomerular colocalization was investigated. Renal and circulating antibodies were matched, and serum levels were compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (anti-a-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including antia-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and anti-a-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria.3.5 g/24 hours and creatinine.1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis.

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Section: Discussionsupporting

confidence: 89%

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2)

Bruschi¹,

Galetti

Sinico

et al. 2015

Journal of the American Society of Nephrology

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“…The implication of antia-enolase IgG2 has been, in particular, addressed on the basis of homology with experimental models of LN and will be discussed below. Anti-annexin AI antibodies in SLE are not new, [34][35][36] because they have been proposed as markers of discoid lupus erythematosus, 34 and more generally, high serum levels have been detected in small series of patients with systemic autoimmune diseases, 14 particularly anti-phospholipid syndrome. 35 The demonstration of specific anti-annexin AI IgG2 in glomeruli emerges as a major finding of this work and strengthens their implication in LN.…”

Section: Discussionmentioning

confidence: 99%

“…Anti-annexin AI antibodies in SLE are not new, [34][35][36] because they have been proposed as markers of discoid lupus erythematosus, 34 and more generally, high serum levels have been detected in small series of patients with systemic autoimmune diseases, 14 particularly anti-phospholipid syndrome. 35 The demonstration of specific anti-annexin AI IgG2 in glomeruli emerges as a major finding of this work and strengthens their implication in LN. Other than antia-enolase and anti-annexin AI, the panel of antibody versus podocyte antigens included proteins of the cytoskeleton, such as vimentin and ezirin/moesin, or cytosol enzymes, such as glutathione synthetase, lactate dehydrogenase, and transketolase.…”

Section: Discussionmentioning

confidence: 99%

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo

Bruschi¹,

Sinico

Moroni

et al. 2014

Journal of the American Society of Nephrology

101

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Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens in renal biopsy samples from patients with LN and determine whether the same autoantibodies can be detected in circulation. Glomeruli were microdissected from biopsy samples of 20 patients with LN and characterized by proteomic techniques. Serum samples from large cohorts of patients with systemic lupus erythematosus (SLE) with and without LN and other glomerulonephritides were tested. Glomerular IgGs recognized 11 podocyte antigens, with reactivity varying by LN pathology. Notably, IgG2 autoantibodies against a-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of a-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti-a-enolase (.15 mg/L) IgG2 and/or anti-annexin AI (.2.7 mg/L) IgG2 were detected in most patients with LN but not patients with other glomerulonephritides, and they identified two cohorts: patients with high anti-a-enolase/low anti-annexin AI IgG2 and patients with low anti-a-enolase/high anti-annexin AI IgG2. Serum levels of both autoantibodies decreased significantly after 12 months of therapy for LN. Anti-a-enolase IgG2 recognized specific epitopes of a-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human a-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against a-enolase and annexin AI predominate in the glomerulus and can be detected in serum.

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“…[7][8][9][10][11][12][13][14] However, a seronegative catastrophic APS has been recently described. 32,33 In this study, we analyzed new possible antigenic target(s) of the antibodies that could be used to identify these patients.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 Indeed, aPLs represent a heterogeneous family of antibodies that react with serum phospholipid-binding plasma proteins, among which ␤ 2 GPI represents the main protein cofactor. 7,8 In addition, protein S, 9,10 protein C, 11 prothrombin, 12 annexin V, 13 or annexin II 14 also have been demonstrated as antigenic targets for these autoantibodies.…”

Section: Introductionmentioning

confidence: 99%