Cited by 180Systemic Lupus Erythematosus ResearchVasculitis and related conditionsSystemic Sclerosis and Related Diseases

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Lessons learned from anti-CD40L treatment in systemic lupus erythematosus patients

Sidiropoulos, P I, Boumpas, D T·2004·Lupus

DOI 10.1191/0961203304lu1032oa

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Abstract

The CD40-CD40L system has pleiotropic effects in a variety of cells and biological processes including immune response, thrombosis and atherogenesis. Within the immune system, these molecules represent a critical link between its humoral and cellular arms. As a result of these attributes and based on preclinical data in animals, anti-CD40L antibodies were tested in a variety of immunologic diseases including idiopathic thrombocytopenic purpura, psoriasis, Crohn's disease, systemic lupus erythematosus and transplantation. Phase I/II studies in humans with lupus nephritis demonstrated reduction of anti-double-stranded DNA (anti-dsDNA) antibodies but not of protective antibodies. Reduction of anti-DNA was associated with increased serum complement levels and reduced glomerular inflammation. As a result of thrombotic effects, observed even in patients negative for anti-cardiolipin antibodies, there is a temporary halt on further human studies. The reasons for the prothrombotic effects are not clear at present but may represent effects on platelets and/or the endothelium. In view of the significant immunomodulatory effects of anti-CD40L treatment in patients with lupus nephritis, the increasing realization of the importance of premature atherosclerosis in lupus and an increasing amount of data supporting a role for the CD40-CD40L interactions in this process, inhibition of this pathway deserves further exploration in lupus.

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Authors: Sidiropoulos, P. I., & Boumpas, D. T.
Affiliations: University of Crete (GR)
Corresponding author: Boumpas, D T
ORCID: Sidiropoulos, P I
Boumpas, D T
Venue: Lupus
Publisher: SAGE Publications
Published: 2004-05
Volume: 13
Issue: 5
Pages: 391-397
ISSN: 0961-2033 (ISSN-L)
1477-0962
DOI: 10.1191/0961203304lu1032oa
OpenAlex: W2074674463
Cited by: 178
References: 75
Citations by year: 2026: 2 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 14 · 2018: 10 · 2017: 8 · 2016: 7 · 2015: 18 · 2014: 11 · 2013: 8 · 2012: 14
FWCI: 6.19
Type: journal article
Language: en
Open access: closed
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Lupus (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
Health Sciences › Medicine › Rheumatology › Vasculitis and related conditions
Health Sciences › Medicine › Rheumatology › Systemic Sclerosis and Related Diseases
Keywords: anti-CD40L antibody, CD40-CD40L interaction, systemic lupus erythematosus, lupus nephritis, anti-dsDNA antibodies, complement system, thrombosis, atherosclerosis, platelets, endothelium, immunomodulation, anticardiolipin antibodies
MeSH terms: Antibodies, Monoclonal, Antibody Formation, B-Lymphocytes, Humans, Immunotherapy, Lupus Erythematosus, Systemic, CD40 Ligand

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Lessons learned from anti-CD40L treatment in systemic lupus erythematosus patients

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