Epitope-Specific Anti-C1q Autoantibodies in Systemic Lupus Erythematosus. Kleer, J. S., Rabatscher, P. A., Weiss, J., Leonardi, J., Vogt, S. B., Kieninger-Gräfitsch, A., Chizzolini, C., Huynh-Do, U., Ribi, C., & Trendelenburg, M. Frontiers in Immunology, 12:761395, January, 2022. ![Epitope-Specific Anti-C1q Autoantibodies in Systemic Lupus Erythematosus [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Objective In patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients. Methods First, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP® microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models. Results The epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p < 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q. Conclusion In this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE.
@article{kleer_epitope-specific_2022,
title = {Epitope-{Specific} {Anti}-{C1q} {Autoantibodies} in {Systemic} {Lupus} {Erythematosus}},
volume = {12},
issn = {1664-3224},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2021.761395/full},
doi = {10.3389/fimmu.2021.761395},
abstract = {Objective
In patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients.
Methods
First, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP® microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models.
Results
The epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p \< 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q.
Conclusion
In this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE.},
urldate = {2022-02-01},
journal = {Frontiers in Immunology},
author = {Kleer, Jessica S. and Rabatscher, Pascal A. and Weiss, Jessica and Leonardi, Joel and Vogt, Severin B. and Kieninger-Gräfitsch, Andrea and Chizzolini, Carlo and Huynh-Do, Uyen and Ribi, Camillo and Trendelenburg, Marten},
month = jan,
year = {2022},
keywords = {Application - Autoimmune Research, PEPperCHIP - Customized - Cyclic constrained, PEPperMAP - Epitope Mapping - Conformational},
pages = {761395},
}
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{"_id":"B7FWpRsxpyM2vWkfY","bibbaseid":"kleer-rabatscher-weiss-leonardi-vogt-kieningergrfitsch-chizzolini-huynhdo-etal-epitopespecificantic1qautoantibodiesinsystemiclupuserythematosus-2022","author_short":["Kleer, J. S.","Rabatscher, P. A.","Weiss, J.","Leonardi, J.","Vogt, S. B.","Kieninger-Gräfitsch, A.","Chizzolini, C.","Huynh-Do, U.","Ribi, C.","Trendelenburg, M."],"bibdata":{"bibtype":"article","type":"article","title":"Epitope-Specific Anti-C1q Autoantibodies in Systemic Lupus Erythematosus","volume":"12","issn":"1664-3224","url":"https://www.frontiersin.org/articles/10.3389/fimmu.2021.761395/full","doi":"10.3389/fimmu.2021.761395","abstract":"Objective In patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients. Methods First, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP® microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models. Results The epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p < 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q. Conclusion In this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE.","urldate":"2022-02-01","journal":"Frontiers in Immunology","author":[{"propositions":[],"lastnames":["Kleer"],"firstnames":["Jessica","S."],"suffixes":[]},{"propositions":[],"lastnames":["Rabatscher"],"firstnames":["Pascal","A."],"suffixes":[]},{"propositions":[],"lastnames":["Weiss"],"firstnames":["Jessica"],"suffixes":[]},{"propositions":[],"lastnames":["Leonardi"],"firstnames":["Joel"],"suffixes":[]},{"propositions":[],"lastnames":["Vogt"],"firstnames":["Severin","B."],"suffixes":[]},{"propositions":[],"lastnames":["Kieninger-Gräfitsch"],"firstnames":["Andrea"],"suffixes":[]},{"propositions":[],"lastnames":["Chizzolini"],"firstnames":["Carlo"],"suffixes":[]},{"propositions":[],"lastnames":["Huynh-Do"],"firstnames":["Uyen"],"suffixes":[]},{"propositions":[],"lastnames":["Ribi"],"firstnames":["Camillo"],"suffixes":[]},{"propositions":[],"lastnames":["Trendelenburg"],"firstnames":["Marten"],"suffixes":[]}],"month":"January","year":"2022","keywords":"Application - Autoimmune Research, PEPperCHIP - Customized - Cyclic constrained, PEPperMAP - Epitope Mapping - Conformational","pages":"761395","bibtex":"@article{kleer_epitope-specific_2022,\n\ttitle = {Epitope-{Specific} {Anti}-{C1q} {Autoantibodies} in {Systemic} {Lupus} {Erythematosus}},\n\tvolume = {12},\n\tissn = {1664-3224},\n\turl = {https://www.frontiersin.org/articles/10.3389/fimmu.2021.761395/full},\n\tdoi = {10.3389/fimmu.2021.761395},\n\tabstract = {Objective \n In patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients. \n \n Methods \n First, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP® microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models. \n \nResults \n The epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p \\< 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q. \n \nConclusion \n In this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE.},\n\turldate = {2022-02-01},\n\tjournal = {Frontiers in Immunology},\n\tauthor = {Kleer, Jessica S. and Rabatscher, Pascal A. and Weiss, Jessica and Leonardi, Joel and Vogt, Severin B. and Kieninger-Gräfitsch, Andrea and Chizzolini, Carlo and Huynh-Do, Uyen and Ribi, Camillo and Trendelenburg, Marten},\n\tmonth = jan,\n\tyear = {2022},\n\tkeywords = {Application - Autoimmune Research, PEPperCHIP - Customized - Cyclic constrained, PEPperMAP - Epitope Mapping - Conformational},\n\tpages = {761395},\n}\n\n","author_short":["Kleer, J. S.","Rabatscher, P. A.","Weiss, J.","Leonardi, J.","Vogt, S. 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