Epitope-Specific Anti-C1q Autoantibodies in Systemic Lupus Erythematosus

Frontiers in Immunology

Immunology

Severin B. Vogt¹  Uyen Huynh-Do²  Carlo Chizzolini³  Camillo Ribi⁴  Jessica Weiss⁵  Pascal A. Rabatscher⁵  Andrea Kieninger-Gräfitsch⁵  Joel Leonardi⁶  Marten Trendelenburg⁶  Jessica S. Kleer⁶ 

[1] Department of Clinical Pharmacology and Toxicology, University Hospital, Basel, Switzerland;Department of Nephrology and Hypertension, University Hospital, Bern, Switzerland;Department of Pathology and Immunology, University Hospital, Geneva, Switzerland;Division of Immunology and Allergy, Department of Internal Medicine, University Hospital, Lausanne, Switzerland;Laboratory of Clinical Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland;Laboratory of Clinical Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland;Division of Internal Medicine, University Hospital, Basel, Switzerland;

关键词: autoantibody(ies);    autoimmune diseases;    complement;    systemic lupus erythematosus (SLE);    lupus nephritis;   

DOI  :  10.3389/fimmu.2021.761395

 received in 2021-08-19, accepted in 2021-12-15,  发布年份 2022

来源: Frontiers

【 摘 要 】

ObjectiveIn 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.MethodsFirst, 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.ResultsThe 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.ConclusionIn 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.

【 授权许可】

Unknown   
Copyright © 2022 Kleer, Rabatscher, Weiss, Leonardi, Vogt, Kieninger-Gräfitsch, Chizzolini, Huynh-Do, Ribi and Trendelenburg