Casein is an Essential Cofactor in Autoantibody Reactivity Directed against the C-Terminal SmD1 Peptide AA 83-119 in Systemic Lupus Erythematosus

Riemekasten, Gabriela; Marell, Jeannette; Hentschel, C; Klein, Roseli Pizzigatti; Burmester, G.-R.; Schoessler, Werner; Hiepe, Falk

doi:10.1078/0171-2985-00202

Cited by 13 publications

(13 citation statements)

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“…With BSA as blocking reagent, a low reactivity of anti-dsDNA and anti-histone antibodies was observed ( fig 1A). Until recently, it seemed that the application of different blocking reagents led to different reactivities of serum samples from patients with SLE with the SmD1(83-119) peptide, 9 whereas we showed that the presence of nucleosomal material in commonly used blocking reagents interfered with the reactivity of anti-chromatin autoantibodies in ELISA. 7 Indeed, DNaseI treatment of the applied blocking reagent-that is, milk and casein-abolished the reactivity of all monoclonal anti-dsDNA antibodies with the SmD1 (83-119) peptide (fig 1A).…”

Section: Resultsmentioning

confidence: 56%

The binding of lupus-derived autoantibodies to the C-terminal peptide (83-119) of the major SmD1 autoantigen can be mediated by double-stranded DNA and nucleosomes

Dieker

Bavel²,

Riemekasten³

et al. 2006

Annals of the Rheumatic Diseases

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Section: Resultsmentioning

confidence: 56%

The binding of lupus-derived autoantibodies to the C-terminal peptide (83-119) of the major SmD1 autoantigen can be mediated by double-stranded DNA and nucleosomes

Dieker

Bavel²,

Riemekasten³

et al. 2006

Annals of the Rheumatic Diseases

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“…[1011] Investigators have also established that as the major protein component of milk, casein is likely an important cofactor for autoantibodies against the SmD1 83-19 peptide and functions through changing the peptide's critical epitope conformation. [7] Further, Dieker et al . [21] mentioned that binding between autoantibodies and SmD1 83-119 can be mediated by dsDNA and nucleosome.…”

Section: Discussionmentioning

confidence: 99%

“…[34] More researchers have exploited various techniques, such as immunoblotting, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA), to increase anti-Sm antibody detection sensitivity. [35678]…”

Section: Introductionmentioning

confidence: 99%

Evaluating Anti-SmD1-amino-acid 83-119 Peptide Reactivity in Children with Systemic Lupus Erythematosus and Other Immunological Diseases

Yang

Zhang

2016

Chinese Medical Journal

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Background:SmD1-amino-acid 83-119 peptide (SmD183-119) is the major epitope of Smith (Sm) antigen, which is specific for adult systemic lupus erythematosus (SLE). The anti-SmD183-119 antibody has exhibited higher sensitivity and specificity than anti-Sm antibody in diagnosing adult SLE. However, the utility of anti-SmD183-119 antibodies remains unclear in children with SLE (cSLE). This study aimed to assess the characteristics of anti-SmD183-119 antibody in the diagnosis of cSLE.Methods:Samples from 242 children with different rheumatological and immunological disorders, including autoimmune diseases (SLE [n = 46] and ankylosing spondylitis [AS, n = 11]), nonautoimmune diseases (Henoch-Schonlein purpura [HSP, n = 60], idiopathic thrombocytopenia purpura [n = 27], hematuria [n = 59], and arthralgia [n = 39]) were collected from Shanghai Children's Medical Center from March 6, 2012 to February 27, 2014. Seventy age- and sex-matched patients were enrolled in this study as the negative controls. All the patients' sera were analyzed for the anti-SmD183-119, anti-Sm, anti-U1-nRNP, anti-double-stranded DNA (dsDNA), anti-nucleosome, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB, anti-Scl-70, and anti-histone antibodies using the immunoblotting assay. The differences in sensitivity and specificity between anti-SmD183-119 and anti-Sm antibodies were compared by Chi-square test. The correlations between anti-SmD183-119 and other auto-antibodies were analyzed using the Spearman's correlation analysis. A value of P < 0.05 was considered statistically significant.Results:Thirty-six out of 46 patients with cSLE were found to be positive for anti-SmD183-119, while 12 patients from the cSLE cohort were found to be positive for anti-Sm. Compared to cSLE, it has been shown that anti-SmD183-119 was only detected in 27.3% of patients with AS and 16.7% of patients with HSP. In comparison with anti-Sm, it has been demonstrated that anti-SmD183-119 had a higher sensitivity (78.3% vs. 26.1%, χ2 = 25.1, P < 0.05) and a lower specificity (90.8% vs. 100%, χ2 = 13.6, P < 0.05) in the diagnosis of cSLE. Further analysis revealed that anti-SmD183-119 antibodies were positively correlated with anti-dsDNA, anti-nucleosome, and anti-histone antibodies in cSLE. Moreover, it has been clearly shown that anti-SmD183-119 was more sensitive than anti-Sm in discriminating autoimmune diseases from nonautoimmune disorders in patients with arthralgia or hematuria.Conclusions:Measurement of anti-SmD183-119 in patients with cSLE has a higher sensitivity and a marginally lower specificity than anti-Sm. It has been suggested that inclusion of anti-SmD183-119 testing in the integrated laboratory diagnosis of cSLE may significantly improve the overall sensitivity in child populations.

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“…The antigens employed in these tests included purified native proteins, recombinant polypeptides or synthetic peptides [79,80,82] and a high degree of clinical accuracy has been reported for immunoassays based on the SmD peptides (SmD1 83-119 and SmD3 108-122) [80][81][82]. The SmD1 peptide has been shown to be dependent on casein as a cofactor for antibody binding [83] and the SmD3 peptide contains an sDMA residue as the key amino acid [79]. Surprisingly, the prevalence of anti-SmD1 83-119 was reported as high as 70% in SLE and up to 20% in related SARD, which is not in agreement with to the known prevalence of anti-Sm antibodies.…”

Section: Anti-sm/rnpmentioning

confidence: 99%

Challenges and Controversies in Autoantibodies Associated with Systemic Rheumatic Diseases

Mähler¹,

Raijmakers²,

Fritzler

2007

CRR

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Since the first identification of self-reactive antibodies in systemic lupus erythematosus and other systemic autoimmune rheumatic diseases, many autoantibodies have been identified as useful probes in molecular and cell biology and as diagnostic and prognostic biomarkers in clinical immunology. Among the autoantigens, double-stranded desoxoribonucleic acid (dsDNA), the Smith antigen (Sm), ribonucleoproteins (RNP), Scl-70 (topoisomerase I), proliferating cell nuclear antigen (PCNA), and others were described as serologic hallmarks in the diagnosis of systemic autoimmune rheumatic diseases. Despite these advances in identifying autoantibody markers, a number of challenges and controversies persist concerning their origin, clinical usefulness and relevance. These include the association between anti-ribosomal P antibodies and clinical features in systemic lupus erythematosus, the disease specificity of several autoantibodies (i.e. chromatin, Jo-1, alpha-fodrin, topo I and CENP), the relationship between the SS-A/Ro52 and SS-A/Ro60 autoantibody system(s) and the detection of anti-RNP/Sm and anti-fibrillarin antibodies.

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Casein is an Essential Cofactor in Autoantibody Reactivity Directed against the C-Terminal SmD1 Peptide AA 83-119 in Systemic Lupus Erythematosus

Cited by 13 publications

References 14 publications

The binding of lupus-derived autoantibodies to the C-terminal peptide (83-119) of the major SmD1 autoantigen can be mediated by double-stranded DNA and nucleosomes

The binding of lupus-derived autoantibodies to the C-terminal peptide (83-119) of the major SmD1 autoantigen can be mediated by double-stranded DNA and nucleosomes

Evaluating Anti-SmD1-amino-acid 83-119 Peptide Reactivity in Children with Systemic Lupus Erythematosus and Other Immunological Diseases

Challenges and Controversies in Autoantibodies Associated with Systemic Rheumatic Diseases

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