{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:32:01Z","timestamp":1760059921956,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Fund, Bulgaria","award":["DN 01\/9","BG16RFPR002-1.014-0017"],"award-info":[{"award-number":["DN 01\/9","BG16RFPR002-1.014-0017"]}]},{"name":"Scientific Research, Innovation, and Digitalization for Intelligent Transformation 2021\u20132027\u201d Programme","award":["DN 01\/9","BG16RFPR002-1.014-0017"],"award-info":[{"award-number":["DN 01\/9","BG16RFPR002-1.014-0017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by tissue damage in multiple organs caused by autoantibodies and the resulting immune complexes. One possible way for complement system contribution to onset of autoimmune disorder could be realized by the impairment of C1q-mediated apoptotic clearance as part of human homeostasis. The capacity of C1q to bind early apoptotic cells could be decreased or even lost in the presence of anti-C1q antibodies. A monoclonal anti-idiotypic single-chain (scFv) antibody was selected from the phage library Griffin1\u201d to recognize anti-C1q autoantibodies, purified from sera of lupus nephritis patients. Lupus-prone MRL\/lpr mice were injected weekly with scFv A1 fragment-binding anti-C1q antibodies. The number of in vitro and ex vivo studies with collected cells, sera, and organs from the treated animals was performed. scFv treatment changed the percentage of different B-, T-, and NK-cell subpopulations as well as plasma cells and plasmablasts in the spleen and bone marrow. An increase in the levels of splenocyte proliferation, anti-C1q antibodies, and the number of plasma cells producing anti-dsDNA and anti-C1q antibodies were also observed in scFv-treated animals. High levels of proteinuria and hematuria combined with unstable levels of IL10 and IFN\u03b3 promote the development of severe lupus and shorten the survival of treated MRL\/lpr mice. Therapy with the scFv A1 antibody resulted in BCR recognition on the surface of anti-C1q-specific B-cells and had a disease progression effect, enhancing lupus symptoms in the MRL\/lpr mouse model of SLE.<\/jats:p>","DOI":"10.3390\/ijms26157048","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T13:35:28Z","timestamp":1753191328000},"page":"7048","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-C1q Autoantibody-Binding Engineered scFv C1q-Mimicking Fragment Enhances Disease Progression in Lupus-Prone MRL\/lpr Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Silviya","family":"Bradyanova","sequence":"first","affiliation":[{"name":"Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8582-9296","authenticated-orcid":false,"given":"Nikolina","family":"Mihaylova","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9046-5914","authenticated-orcid":false,"given":"Nikola","family":"Ralchev","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4419-1603","authenticated-orcid":false,"given":"Alexandra","family":"Kapogianni","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biology, Sofia University \u201cSt. Kliment Ohridski\u201d, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4375-5115","authenticated-orcid":false,"given":"Ginka","family":"Cholakova","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biology, Sofia University \u201cSt. Kliment Ohridski\u201d, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalina","family":"Nikolova-Ganeva","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3308-4154","authenticated-orcid":false,"given":"Ivanka","family":"Tsacheva","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biology, Sofia University \u201cSt. Kliment Ohridski\u201d, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey","family":"Tchorbanov","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.33590\/emjrheumatol\/10311457","article-title":"Cytokines and Inflammatory Mediators in Systemic Lupus Erythematosus","volume":"5","author":"Rojas","year":"2018","journal-title":"EMJ Rheumatol."},{"key":"ref_2","unstructured":"Tsokos, G.C. (2016). Chapter 8\u2014Overview of the Pathogenesis of Systemic Lupus Erythematosus. Systemic Lupus Erythematosus, Academic Press."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"677","DOI":"10.2217\/bmm-2016-0379","article-title":"Novel biomarkers for systemic lupus erythematosus","volume":"11","author":"Zeng","year":"2017","journal-title":"Biomark. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dossybayeva, K., Abdukhakimova, D., and Poddighe, D. (2020). Basophils and Systemic Lupus Erythematosus in Murine Models and Human Patients. Biology, 9.","DOI":"10.3390\/biology9100308"},{"key":"ref_5","first-page":"1","article-title":"Anti-CD20 monoclonal antibodies in Systemic Lupus Erythematosus","volume":"69","author":"Shah","year":"2021","journal-title":"Biol. J. Int. Assoc. Biol. Stand."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e000199","DOI":"10.1136\/lupus-2016-000199","article-title":"Mouse models of lupus: What they tell us and what they don\u2019t","volume":"5","author":"Richard","year":"2018","journal-title":"Lupus Sci. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1177\/0300985810370005","article-title":"Mouse models of systemic lupus erythematosus reveal a complex pathogenesis","volume":"47","author":"Rottman","year":"2010","journal-title":"Vet. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/ar3433","article-title":"Lipsky PE Mechanisms of B cell autoimmunity in SLE","volume":"13","author":"Giesecke","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.semnephrol.2006.09.007","article-title":"T cells and B cells in lupus nephritis","volume":"27","author":"Foster","year":"2007","journal-title":"Semin. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tai, Y., Wang, Q., Korner, H., Zhang, L., and Wei, W. (2018). Molecular mechanisms of T cells activation by dendritic cells in autoimmune diseases. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00642"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wilkinson, M.G.L., and Rosser, E.C. (2019). B cells as a therapeutic target in paediatric rheumatic disease. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00214"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.4049\/jimmunol.179.5.3351","article-title":"Depletion of B cells in murine lupus: Efficacy and resistance","volume":"179","author":"Ahuja","year":"2007","journal-title":"J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"eaav1648","DOI":"10.1126\/scitranslmed.aav1648","article-title":"Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus","volume":"11","author":"Kansal","year":"2009","journal-title":"Sci. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/art.34359","article-title":"Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: The Lupus Nephritis Assessment with Rituximab study","volume":"64","author":"Rovin","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1136\/annrheumdis-2012-202760","article-title":"Efficacy and safety of epratuzumab in patients with moderate\/severe active systemic lupus erythematosus: Results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study","volume":"73","author":"Wallace","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1177\/0961203316645205","article-title":"Anti-C1q in systemic lupus erythematosus","volume":"25","author":"Stojan","year":"2016","journal-title":"Lupus"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Csorba, K., Schirmbeck, L.A., Tuncer, E., Ribi, C., Roux-Lombard, P., Chizzolini, C., Huynh-Do, U., Vanhecke, D., and Trendelenburg, M. (2019). Anti-C1q Antibodies as Occurring in Systemic Lupus Erythematosus Could Be Induced by an Epstein-Barr Virus-Derived Antigenic Site. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02619"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.4049\/jimmunol.1501659","article-title":"Anti-C1q Autoantibodies from Systemic Lupus Erythematosus Patients Induce a Proinflammatory Phenotype in Macrophages","volume":"196","author":"Thanei","year":"2016","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"812","DOI":"10.4049\/jimmunol.171.2.812","article-title":"Modular Organization of the Carboxyl-Terminal, Globular Head Region of Human C1q A, B, and C Chains","volume":"171","author":"Kishore","year":"2003","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Todorova, N., Rangelov, M., Bogoeva, V., Stoyanova, V., Yordanova, A., Nikolova, G., Georgiev, H., Dimitrova, D., Mohedin, S., and Stoyanova, K. (2021). Anti-Idiotype scFv Localizes an Autoepitope in the Globular Domain of C1q. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158288"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3587","DOI":"10.1002\/eji.200737143","article-title":"Selective silencing of DNA-specific B lymphocytes delays lupus activity in MRL\/lpr mice","volume":"37","author":"Tchorbanov","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e12915","DOI":"10.1111\/sji.12915","article-title":"Monoclonal antibody therapy that targets phospholipid-binding protein delays lupus activity in MRL\/lpr mice","volume":"92","author":"Mihaylova","year":"2020","journal-title":"Scand. J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00005-021-00624-7","article-title":"Anti-ANX A1 Antibody Therapy in MRL\/lpr Murine Model of Systemic Lupus Erythematosus","volume":"69","author":"Bradyanova","year":"2021","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s00281-005-0007-y","article-title":"Antibodies against C1q in patients with systemic lupus erythematosus","volume":"27","author":"Trendelenburg","year":"2005","journal-title":"Springer Semin. Immunopathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1172\/JCI200421075","article-title":"Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes","volume":"114","author":"Trouw","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1016\/j.molimm.2006.09.009","article-title":"Detection of autoantibodies against the globular domain of human C1q in the sera of systemic lupus erythematosus patients","volume":"44","author":"Tsacheva","year":"2007","journal-title":"Mol. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.molimm.2015.05.010","article-title":"C1q, antibodies and anti-C1q autoantibodies","volume":"68","author":"Beurskens","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.cell.2018.07.010","article-title":"Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging","volume":"174","author":"Goltsev","year":"2018","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1084\/jem.180.4.1295","article-title":"The role of B cells in lpr\/lpr-induced autoimmunity","volume":"180","author":"Shlomchik","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Liu, M., Liang, S., and Zhang, C. (2021). NK Cells in Autoimmune Diseases: Protective or Pathogenic?. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.624687"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/intimm\/dxl047","article-title":"Spontaneous B cell hyperactivity in autoimmune-prone MRL mice","volume":"18","author":"Nijnik","year":"2006","journal-title":"Int. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kleer, J.S., Rabatscher, P.A., Weiss, J., Leonardi, J., Vogt, S.B., Kieninger-Gr\u00e4fitsch, A., Chizzolini, C., Huynh-Do, U., Ribi, C., and Trendelenburg, M. (2022). Epitope-Specific Anti-C1q Autoantibodies in Systemic Lupus Erythematosus. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.761395"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6941","DOI":"10.1038\/s41467-023-42541-7","article-title":"Antigen presentation by B cells enables epitope spreading across an MHC barrier","volume":"14","author":"Wittenborn","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jaut.2013.06.002","article-title":"Anti-DNA antibodies cross-react with C1q","volume":"44","author":"Franchin","year":"2013","journal-title":"J. Autoimmun."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kapogianni, A., Radulova, G., Donev, V., Videv, P., Cholakova, G., Iliev, S., Ivanova, A., Bogoeva, V., and Tsacheva, I. (2025). Characterization of the binding of the globular domains of the complement component C1q to phosphatidylserine. Int. J. Biol. Macromol., 291.","DOI":"10.1016\/j.ijbiomac.2024.139116"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/labinvest.3700468","article-title":"IL-10 regulation of lupus in the NZM2410 murine model","volume":"86","author":"Blenman","year":"2006","journal-title":"Lab. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.4049\/jimmunol.2100565","article-title":"IL-10 as a Th2 Cytokine: Differences Between Mice and Humans","volume":"207","author":"Rasquinha","year":"2021","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s12033-021-00363-2","article-title":"Autoinduction as Means for Optimization of the Heterologous Expression of Recombinant Single-Chain Fv (scFv) Antibodies","volume":"63","author":"Nikolova","year":"2021","journal-title":"Mol. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/08916934.2017.1300884","article-title":"Annexin A1 as a target for managing murine pristane-induced systemic lupus erythematosus","volume":"50","author":"Mihaylova","year":"2017","journal-title":"Autoimmunity"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7048\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:13:59Z","timestamp":1760033639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7048"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,22]]},"references-count":39,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26157048"],"URL":"https:\/\/doi.org\/10.3390\/ijms26157048","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,7,22]]}}}