Serum IgG2 antibody multicomposition in systemic lupus erythematosus and lupus nephritis (Part 1): cross-sectional analysis
Abstract Objectives Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antig...
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| Published in | Rheumatology Vol. 60; no. 7; pp. 3176 - 3188 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Oxford University Press (OUP)
29.12.2020
Oxford University Press Oxford Publishing Limited (England) |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1462-0324 1462-0332 1462-0332 |
| DOI | 10.1093/rheumatology/keaa767 |
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| Abstract | Abstract
Objectives
Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis.
Methods
A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non‐commercial techniques.
Results
The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low–medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0–12 months), and high levels at T0–1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions.
Conclusion
Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients.
Trial registration
The Zeus study was registered at https://clinicaltrials.gov, NCT02403115. |
|---|---|
| AbstractList | Objectives Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis. Methods A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non‐commercial techniques. Results The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low–medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0–12 months), and high levels at T0–1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions. Conclusion Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients. Trial registration The Zeus study was registered at https://clinicaltrials.gov, NCT02403115. Abstract Objectives Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis. Methods A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non‐commercial techniques. Results The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low–medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0–12 months), and high levels at T0–1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions. Conclusion Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients. Trial registration The Zeus study was registered at https://clinicaltrials.gov, NCT02403115. Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis. A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercial techniques. The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low-medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0-12 months), and high levels at T0-1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions. Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients. The Zeus study was registered at https://clinicaltrials.gov, NCT02403115. Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis.OBJECTIVESSerum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis.A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercial techniques.METHODSA total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercial techniques.The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low-medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0-12 months), and high levels at T0-1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions.RESULTSThe presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low-medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0-12 months), and high levels at T0-1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions.Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients.CONCLUSIONNephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients.The Zeus study was registered at https://clinicaltrials.gov, NCT02403115.TRIAL REGISTRATIONThe Zeus study was registered at https://clinicaltrials.gov, NCT02403115. |
| Author | Andrea Petretto Giacomo Garibotto Leda Cipriani Angela Tincani Stefano Volpi Marco Prunotto Angelo A. Manfredi Giulia Pazzola Barbara Trezzi Domenico Santoro Giuseppe A. Ramirez Maurizio Bruschi Isabella Pisani Paride Fenaroli Simone Negrini Giuseppe Murdaca Federico Pratesi Enrico Verrina Gian Marco Ghiggeri Pasquale Esposito Carlomaurizio Montecucco Giacomo Emmi Gabriella Moroni Angelo Ravelli Augusto Vaglio Andrea Angeletti Franco Franceschini Micaela Fredi Giovanni Candiano Marcello Bagnasco Marta Mosca Giampaola Pesce Valentina Binda Francesco Locatelli Paola Migliorini Renato Alberto Sinico Lorenzo Cavagna Ilaria Cavazzana Francesco Scolari |
| AuthorAffiliation | 5 Nephrology and Dialysis Unit, Meyer Children’s Hospital , Firenze 15 Division of Nephrology, University of Genoa and Policlinico San Martino , Genoa 22 Division of Paediatric Rheumatology 10 Nephrology and Dialysis, Arciospedale Santa Maria Nuova , Reggio Emilia 1 Laboratory of Molecular Nephrology, Division of Paediatric Rheumatology and Division of Nephrology, Dialysis and Transplantation, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini , Genoa 4 Rheumatology and Clinical Immunology, ASST SpedaliCivili and Università of Brescia , Brescia 14 Department of Internal Medicine, University of Genoa , Genoa 23 Division of Nephrology, Dialysis and Transplantation, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini , Genoa, Italy 8 Core Facilities-Proteomics Laboratory, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini , Genoa 21 School of Pharmaceutical Sciences, University of Geneva , Geneva, Switze |
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| BackLink | https://cir.nii.ac.jp/crid/1873398393023431680$$DView record in CiNii https://www.ncbi.nlm.nih.gov/pubmed/33374003$$D View this record in MEDLINE/PubMed |
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| Contributor | Vaglio, A Ravelli, A Scolari, F Mosca, M Tincani, A Garibotto, G Ghiggeri, G. M Franceschini, F Bagnasco, M Cavagna, L Emmi, G Prunotto, M Murdaca, G Negrini, S Esposito, P Bruschi, M Verrina, E Cavazzana, I Pisani, I Fenaroli, P Binda, V Pesce, G Sinico, R. A Petretto, A Manfredi, A Candiano, G Migliorini, P Trezzi, B Santoro, D Volpi, S Angeletti, A Ramirez, G. A Pazzola, G Montecucco, C Fredi, M Pratesi, F Locatelli, F Cipriani, L Moroni, G |
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| Copyright | The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com. The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com |
| Copyright_xml | – notice: The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com 2020 – notice: The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com. – notice: The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com |
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| Issue | 7 |
| Keywords | LN anti-ENO1 antibodies SLE biomarkers anti-Histone 2A antibodies anti-C1q antibodies |
| Language | English |
| License | This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com. |
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| PublicationPlace | England |
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| PublicationTitle | Rheumatology |
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| PublicationYear | 2020 |
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| Snippet | Abstract
Objectives
Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show... Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity... Objectives Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher... |
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| SubjectTerms | Adolescent Adult Annexin A1 anti-C1q antibodie anti-C1q antibodies anti-C1q antibodies; anti-ENO1 antibodies; anti-Histone 2A antibodies; biomarkers; LN; SLE anti-C1q antibodies; anti-ENO1 antibodies; anti-Histone 2A antibodies; biomarkers; LN; SLE; Adolescent; Adult; Annexin A1; Antibodies, Antinuclear; Antibody Specificity; Antiphospholipid Syndrome; Arthritis, Rheumatoid; Biomarkers, Tumor; Complement C1q; Cross-Sectional Studies; DNA; DNA-Binding Proteins; Female; Histones; Humans; Immunoglobulin G; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Middle Aged; Nucleosomes; Phosphopyruvate Hydratase; Tumor Suppressor Proteins; Undifferentiated Connective Tissue Diseases; Young Adult anti-C1q antibodies; anti-ENO1 antibodies; anti-Histone 2A antibodies; biomarkers; lupus nephritis; systemic lupus erythematosus Anti-DNA antibodies anti-ENO1 antibodie anti-ENO1 antibodies anti-Histone 2A antibodie anti-Histone 2A antibodies Antibodies Antibodies, Antinuclear Antibody Specificity Antigens Antinuclear Antiphospholipid Syndrome Arthritis Arthritis, Rheumatoid biomarker biomarkers Biomarkers, Tumor Clinical Science Complement C1q Cross-Sectional Studie Cross-Sectional Studies DNA DNA-Binding Protein DNA-Binding Proteins Female Histone Histones Human Humans Immunoglobulin G Intracellular LN LN, SLE, biomarkers, anti-ENO1 antibodies, anti-Histone 2A antibodies, anti-C1q antibodies LN; SLE; anti-C1q antibodies; anti-ENO1 antibodies; anti-Histone 2A antibodies; biomarkers Lupus Lupus Erythematosus Lupus Erythematosus, Systemic Lupus Nephriti Lupus Nephritis Male Middle Aged Nucleosome Nucleosomes Phosphopyruvate Hydratase Radioimmunoassay Rheumatoid Serum levels SLE Systemic Systemic lupus erythematosus Tumor Tumor Suppressor Protein Tumor Suppressor Proteins Undifferentiated Connective Tissue Disease Undifferentiated Connective Tissue Diseases Young Adult |
| Title | Serum IgG2 antibody multicomposition in systemic lupus erythematosus and lupus nephritis (Part 1): cross-sectional analysis |
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