Measurement of serum C3 and C4 has been used for several decades to monitor disease activity in patients with SLE. Despite the limited utility and recognized weaknesses of these assays, they have remained the gold standard during an era of unprecedented discovery in the complement field. The current urgent need for lupus biomarkers warrants efforts to mine the complement system for assays superior to serum C3 and C4. Recent studies of soluble and cell-bound complement activation products hold promise for achieving this goal.
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Cell-bound complement activation products in antiphospholipid antibody-positive patients without other systemic autoimmune rheumatic diseases.
Front Immunol
October 2024
Clinical Affairs, Exagen, Vista, CA, United States.
Article Synopsis
- The study focused on understanding how complement activation occurs in patients with antiphospholipid antibodies (aPL) but without other autoimmune diseases, analyzing various complement activation markers.
- Researchers found that a considerable portion of the aPL-positive patients had abnormal levels of cell-bound complement activation products (CB-CAPs), indicating different profiles and clinical manifestations of the disease.
- The results suggest that CB-CAPs might be better indicators of disease activity and thrombosis risk than traditional C3/C4 complement levels in these patients.
Earlier vs. later time period of COVID-19 infection and emergent autoimmune signs, symptoms, and serologies.
J Autoimmun
September 2024
Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Rd., Boston, MA, 02115, USA.
Objective: Autoantibodies and autoimmune diseases after SARS-CoV-2 infection are widely reported. Given evolving variants, milder infections, and increasing population vaccination, we hypothesized that SARS-CoV-2 infection earlier in the pandemic would be associated with more autoimmune connective tissue disease (CTD) symptoms and immunologic abnormalities.
Methods: Patients ≥18 years old with COVID-19 3/1/2020-8/15/2022 completed the CTD Screening Questionnaire and were tested for 27 autoimmune serologies, SARS-CoV-2 serologies, cell-bound complement activation products (CB-CAPs), and T and B lymphocyte immunophenotypes by flow cytometry.
Complement biomarkers in the antiphospholipid syndrome - Approaches to quantification and implications for clinical management.
Clin Immunol
December 2023
Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address:
Complement is a major driver of antiphospholipid syndrome (APS) and a promising therapeutic target in refractory and catastrophic APS. Complement testing in APS is largely limited to research settings, and reliable, rapid-turnaround biomarkers are needed to predict those at risk for adverse clinical outcomes and most likely to benefit from complement inhibition. We review complement biomarkers and their association with thrombosis and obstetric outcomes, including: (i) complement proteins and activation fragments in the fluid phase; (ii) assays that evaluate complement on cell membranes (e.
View Article and Find Full Text PDFMeasurement of Trogocytosis: Quantitative Analyses Validated with Rigorous Controls.
Curr Protoc
October 2023
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia.
Trogocytosis is a process in which receptors on acceptor cells remove and internalize cognate ligands from donor cells. Trogocytosis has a profound and negative impact on mAb-based cancer immunotherapy, as seen in the treatment of chronic lymphocytic leukemia (CLL) with CD20 mAbs, such as rituximab (RTX) and ofatumumab (OFA). Our clinical observations of RTX/OFA-mediated loss of the CD20 target from circulating CLL cells have been replicated in our in vitro studies.
View Article and Find Full Text PDFExploration of complement split products in plasma and urine as biomarkers of kidney graft rejection.
Immunobiology
July 2023
Dept. of Nephrology, Odense University Hospital, Kløvervænget 6, 5000 Odense, Denmark; Dept. of Clinical Research, University of Southern Denmark, J.B. Winsløwsvej 19, 5000 Odense, Denmark. Electronic address:
Introduction: The complement system, consisting of more than thirty different soluble and cell-bound proteins, exerts essential functions both in the innate and adaptive immune systems and is believed to be an important contributor to allograft injury in kidney transplantation. The anaphylatoxins C3a and C5a are powerful chemoattractants, recruiting immune effector cells toward the site of complement activation and enhance T-cell response, while C3dg binding to CR2 on B-cells, enhances B-cell immunity at several stages of the B-cell differentiation. Complement split products in plasma and urine could reflect ongoing inflammation and tissue injury.
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