Publications
2009
Schett G, Dumortier H, Hoefler E, Muller S, Steiner G
B cell epitopes of the heterogeneous nuclear ribonucleoprotein A2: identification of a new specific antibody marker for active lupus disease Article de journal
Dans: Annals of the Rheumatic Diseases, vol. 68, no. 5, p. 729–735, 2009, ISSN: 1468-2060.
Résumé | Liens | BibTeX | Étiquettes: Autoantibodies, B-Lymphocyte, Biomarkers, Dumortier, Enzyme-Linked Immunosorbent Assay, Epitopes, Female, Follow-Up Studies, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Humans, I2CT, Lupus Erythematosus, Male, Rheumatic Diseases, Severity of Illness Index, Systemic, Team-Dumortier
@article{schett_b_2009,
title = {B cell epitopes of the heterogeneous nuclear ribonucleoprotein A2: identification of a new specific antibody marker for active lupus disease},
author = {G Schett and H Dumortier and E Hoefler and S Muller and G Steiner},
doi = {10.1136/ard.2007.087502},
issn = {1468-2060},
year = {2009},
date = {2009-05-01},
journal = {Annals of the Rheumatic Diseases},
volume = {68},
number = {5},
pages = {729--735},
abstract = {OBJECTIVES: Autoantibody formation and T cell reactivity against the heterogeneous nuclear ribonucleoprotein A2 (hnRNP-A2) has been observed in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Since no differences in epitope recognition were reported and the usefulness of anti-hnRNP-A2 antibodies as diagnostic markers of SLE is unknown, it was our objective to characterise linear B cell epitopes of hnRNP-A2 and to relate the anti-hnRNP-A2 antibody responses to disease activity and clinical features of SLE.
METHODS: Sequential serum samples from 15 patients with SLE and sera from patients with other rheumatic diseases and healthy subjects were investigated by ELISA for autoantibody reactivities against a set of 13 overlapping peptides spanning the RNA-binding region of hnRNP-A2. Antibody reactivity against the complete protein was determined by western immunoblotting and ELISA. SLE disease activity was assessed by European Consensus Lupus Activity Measure scores, by SLE Index scores and the British Isles Lupus Assessment index.
RESULTS: Anti-peptide antibody reactivities were found in 60% of SLE sera but in only 5% of control samples, and were mainly directed to four peptides, one of which (p155-175) appeared to be immunodominant. Antibodies to p155-175 were exclusively seen in patients with SLE and correlated with clinical disease activity as well as kidney and skin involvement. No correlations were found for the other anti-peptide antibody responses.
CONCLUSION: Peptide p155-175 encompasses a disease-specific immunodominant epitope of hnRNP-A2. Since antibodies to p155-175 correlate with disease activity and nephritis, they may be useful as markers for active SLE.},
keywords = {Autoantibodies, B-Lymphocyte, Biomarkers, Dumortier, Enzyme-Linked Immunosorbent Assay, Epitopes, Female, Follow-Up Studies, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Humans, I2CT, Lupus Erythematosus, Male, Rheumatic Diseases, Severity of Illness Index, Systemic, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
METHODS: Sequential serum samples from 15 patients with SLE and sera from patients with other rheumatic diseases and healthy subjects were investigated by ELISA for autoantibody reactivities against a set of 13 overlapping peptides spanning the RNA-binding region of hnRNP-A2. Antibody reactivity against the complete protein was determined by western immunoblotting and ELISA. SLE disease activity was assessed by European Consensus Lupus Activity Measure scores, by SLE Index scores and the British Isles Lupus Assessment index.
RESULTS: Anti-peptide antibody reactivities were found in 60% of SLE sera but in only 5% of control samples, and were mainly directed to four peptides, one of which (p155-175) appeared to be immunodominant. Antibodies to p155-175 were exclusively seen in patients with SLE and correlated with clinical disease activity as well as kidney and skin involvement. No correlations were found for the other anti-peptide antibody responses.
CONCLUSION: Peptide p155-175 encompasses a disease-specific immunodominant epitope of hnRNP-A2. Since antibodies to p155-175 correlate with disease activity and nephritis, they may be useful as markers for active SLE.
2008
Muller Sylviane, Monneaux Fanny, Schall Nicolas, Rashkov Rasho K, Oparanov Boycho A, Wiesel Philippe, Geiger Jean-Marie, Zimmer Robert
Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial Article de journal
Dans: Arthritis and Rheumatism, vol. 58, no. 12, p. 3873–3883, 2008, ISSN: 0004-3591.
Résumé | Liens | BibTeX | Étiquettes: Adolescent, Adult, Aged, Antibodies, Antinuclear, C-Reactive Protein, DNA, Female, Humans, I2CT, Immunotherapy, Lupus Erythematosus, Male, Middle Aged, Monneaux, Peptide Fragments, Peptides, Severity of Illness Index, Spliceosomes, Systemic, Team-Dumortier, Treatment Outcome, Young Adult
@article{muller_spliceosomal_2008,
title = {Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial},
author = {Sylviane Muller and Fanny Monneaux and Nicolas Schall and Rasho K Rashkov and Boycho A Oparanov and Philippe Wiesel and Jean-Marie Geiger and Robert Zimmer},
doi = {10.1002/art.24027},
issn = {0004-3591},
year = {2008},
date = {2008-01-01},
journal = {Arthritis and Rheumatism},
volume = {58},
number = {12},
pages = {3873--3883},
abstract = {OBJECTIVE: To assess the safety, tolerability, and efficacy of spliceosomal peptide P140 (IPP-201101; sequence 131-151 of the U1-70K protein phosphorylated at Ser140), which is recognized by lupus CD4+ T cells, in the treatment of patients with systemic lupus erythematosus (SLE).
METHODS: An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor alpha were measured by ELISA and nephelometry.
RESULTS: IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 x 200 microg IPP-201101 (group 1), but only in 1 patient in the group receiving 3 x 1,000 microg IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration.
CONCLUSION: IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.},
keywords = {Adolescent, Adult, Aged, Antibodies, Antinuclear, C-Reactive Protein, DNA, Female, Humans, I2CT, Immunotherapy, Lupus Erythematosus, Male, Middle Aged, Monneaux, Peptide Fragments, Peptides, Severity of Illness Index, Spliceosomes, Systemic, Team-Dumortier, Treatment Outcome, Young Adult},
pubstate = {published},
tppubtype = {article}
}
METHODS: An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor alpha were measured by ELISA and nephelometry.
RESULTS: IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 x 200 microg IPP-201101 (group 1), but only in 1 patient in the group receiving 3 x 1,000 microg IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration.
CONCLUSION: IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.