Simultaneous Positivity for Anti-DNA, Anti-Nucleosome and Anti-Histone Antibodies is a Marker for More Severe Lupus Nephritis

Sui, Manshu; Lin, Qingyuan; Xu, Zhaozhen; Han, Xiaojing; Xie, Ruiqin; Jia, Xiuzhi; Guo, Xin; Zhang, Weihua; Xiuru, Guan; Ren, Huan

doi:10.1007/s10875-012-9825-6

Cited by 49 publications

(46 citation statements)

References 43 publications

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“…Differences in anti-histone reactivity have occasionally been associated with particular disease manifestations in SLE patients, including neuropsychiatric lupus [37], discoid lupus [42], and incomplete lupus syndromes [43]. Furthermore, anti-chromatin, anti-dsDNA, and anti-histone reactivity are unequivocally correlated to renal involvement [43], while simultaneous positivity for all three markers has been suggested as a possible marker for severe lupus nephritis [44]. However, although anti-chromatin and anti-histone reactivity are related to renal involvement, measuring these reactivities using conventional chromatin or histones as substrates, is not considered to be useful to differentiate SLE with nephritis from SLE without nephritis [45].…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis

et al. 2016

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Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features. Plasma from SLE patients with and without lupus nephritis, disease controls, and healthy controls, were tested in ELISA with histone H4 peptide acetylated at lysines 8, 12 and 16 (H4pac), H2B peptide acetylated at lysine 12 (H2Bpac), H3 peptide trimethylated at lysine 27 (H3pme), and their unmodified equivalents. SLE patients displayed a higher reactivity with the modified equivalent of each peptide. Reactivity with H4pac showed both a high sensitivity (89%) and specificity (91%) for SLE, while H2Bpac exhibited a high specificity (96%) but lower sensitivity (69%). Reactivity with H3pme appeared not specific for SLE. Anti-H4pac and anti-H2Bpac reactivity demonstrated a high correlation with disease activity. Moreover, patients reacting with multiple modified histone peptides exhibited higher SLEDAI and lower C3 levels. SLE patients with renal involvement showed higher reactivity with H2B/H2Bpac and a more pronounced reactivity with the modified equivalent of H3pme and H2Bpac. In conclusion, reactivity with H4pac and H2Bpac is specific for SLE patients and correlates with disease activity, whereas reactivity with H2Bpac is in particular associated with lupus nephritis.

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Section: Discussionmentioning

confidence: 99%

Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis

et al. 2016

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“…Anti-nuclear antibody is a disease activity marker in SLE [16] and in lupus nephritis [17], with a positivity rate of 95% to 100% at disease onset [18]. …”

Section: Discussionmentioning

confidence: 99%

Association between IgG4 Autoantibody and Complement Abnormalities in Systemic Lupus Erythematosus

Guo

Cai

et al. 2016

Mediators of Inflammation

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In order to investigate the association between IgG4 autoantibody and complement abnormalities in systemic lupus erythematosus (SLE), 72 newly diagnosed SLE patients, 67 rheumatoid arthritis (RA) patients, and 41 healthy normals were employed. Serum levels of antinuclear IgG4 and IgG4-specific IgM-rheumatoid factor (RF) were measured, and the correlations between serum levels of antinuclear IgG4 and several clinical parameters were analyzed. Also, the levels of IgG subclasses, C1q, and C3 deposition in lupus nephritis (LN) were detected. The results showed that serum levels of antinuclear IgG4 were higher in SLE patients relative to healthy normals (P < 0.01). Serum levels of antinuclear IgG4 in SLE patients were positively correlated with serum levels of total IgG4, albumin, and C3 (r = 0.61, P < 0.05; r = 0.40, P < 0.05; and r = 0.54, P < 0.05, resp.) and negatively correlated with 24-hour urinary protein (r = 0.49, P < 0.05). Serum levels of IgG4-specific IgM-RF were higher in RA patients than in SLE patients (P < 0.001). Also, the ratio of the deposition score for IgG4/(IgG1 + IgG2 + IgG3 + IgG4) was negatively correlated with the score for C1q and C3 deposition in LN (r = 0.34, P < 0.05; r = 0.51, P < 0.01, resp.). In summary, the IgG4 autoantibody may dampen the inflammatory response in SLE, thus maybe providing a novel therapeutic target for SLE.

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“…[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. IgG2 were unexpected, because these antibodies are weak complement activators compared with IgG1 and IgG3.…”

Section: Discussionmentioning

confidence: 99%

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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Simultaneous Positivity for Anti-DNA, Anti-Nucleosome and Anti-Histone Antibodies is a Marker for More Severe Lupus Nephritis

Abstract: Our data indicate a strong association between the 3-pos and renal disease activities, especially proliferative glomerulonephritis. The ability of 3-pos to predict renal flares may lead to major additional benefits in the follow-up of these patients.

Cited by 49 publications

References 43 publications

Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis

Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis

Association between IgG4 Autoantibody and Complement Abnormalities in Systemic Lupus Erythematosus

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

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