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

Sidiropoulos, P I; Boumpas, D T

doi:10.1191/0961203304lu1032oa

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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Monoclonal antibodies against CD154, known to cause thromboembolic events in halted clinical trials, were tested in the VoC model at relevant concentrations and successfully induced thrombosis.
“As an example, monoclonal antibodies against CD154, known to cause thromboembolic events in halted clinical trials (Sidiropoulos and Boumpas, 2004), were tested in the VoC model at relevant concentrations and successfully induced thrombosis (Barrile et al., 2018).”
From Considering future qualification for regulatory science in the early development of microphysiological systems: a case study of microthrombosis in a Vessel-on-Chip (2024) · cites this paper as Sidiropoulos and Boumpas, 2004

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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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