Complement-amplified thrombotic microangiopathy in systemic lupus erythematosus and lupus nephritis: a systematic review of 78 reported patients
- 1Department of Rheumatology and Immunology, Peking University International Hospital , ,
Abstract
Background: Thrombotic microangiopathy (TMA) complicating systemic lupus erythematosus (SLE) and lupus nephritis (LN) spans immune thrombotic thrombocytopenic purpura, anti-phospholipid-associated microangiopathy, secondary endothelial injury, and complement-amplified/atypical hemolytic uremic syndrome (aHUS)-like phenotypes. The boundaries remain uncertain, and treatment evidence is dominated by selectively published cases.
Methods: In this PROSPERO-registered systematic review (CRD420261409684), we searched PubMed, Embase, and Web of Science through to 17 March 2026, verified the source identity and eligibility, and performed a PubMed-only update through to 14 August 2026. We reconstructed patient-level reports by phenotype, competing mechanisms, complement-related evidence, treatment, and outcome. We included citable published abstracts when patient-level data were extractable but analyzed them as a lower-information stratum rather than as equivalent to full texts. Analyses were descriptive. We did not include China National Knowledge Infrastructure (CNKI) because no verifiable search record was available. One reviewer performed the screening, extraction, and appraisal. We report both as protocol deviations.
Results: We included 56 sources describing 78 patients: in total, 39 full-text sources/61 patients and 17 published abstract sources/17 patients. There were 56 female patients (71.8%), and the median age was 24.5 years. Source-adjudicated microangiopathic hemolysis, thrombocytopenia, acute kidney injury/renal failure, strict TMA identified on kidney biopsy, and dialysis/renal replacement therapy (RRT) were present in 71 (91.0%), 74 (94.9%), 67 (85.9%), 42 (53.8%), and 46 (59.0%), respectively. Low C3/C4 levels were reported in 55 (70.5%), strict T2 complement evidence in 1 (1.3%), and index event terminal/tissue activation in 6 (7.7%). Complement inhibitors were reported in 60 (76.9%) and renal and hematologic improvements in 49 (62.8%) and 65 (83.3%), respectively. Certainty was very low, and treatment comparisons were not estimable.
Conclusions: SLE/LN-associated TMA is heterogeneous, and complement may act as a driver, an amplifier, or an epiphenomenon. Case-based evidence supports rigorous mechanistic adjudication and biomarker-rich registries, but cannot establish incidence, prognosis, comparative efficacy, or universal treatment duration.
Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261409684 , identifier CRD420261409684.
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BibTeX
@article{li2026complementamplified,
title = {{Complement-amplified thrombotic microangiopathy in systemic lupus erythematosus and lupus nephritis: a systematic review of 78 reported patients}},
author = {Sheng-Guang Li and Ruohan Yu and Yanfeng Zhang and Lina Zhang and Jing Zhang and Yadan Zou and Ji Li and Ting Long and Xujie You},
journal = {Frontiers in immunology},
year = {2026},
month = sep,
doi = {10.3389/fimmu.2026.1940769},
url = {https://europepmc.org/article/PMC/PMC13661993},
note = {CC BY},
}
RIS
TY - JOUR
TI - Complement-amplified thrombotic microangiopathy in systemic lupus erythematosus and lupus nephritis: a systematic review of 78 reported patients
AU - Sheng-Guang Li
AU - Ruohan Yu
AU - Yanfeng Zhang
AU - Lina Zhang
AU - Jing Zhang
AU - Yadan Zou
AU - Ji Li
AU - Ting Long
AU - Xujie You
PY - 2026
DA - 2026/09/30
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1940769
UR - https://europepmc.org/article/PMC/PMC13661993
AB - Background: Thrombotic microangiopathy (TMA) complicating systemic lupus erythematosus (SLE) and lupus nephritis (LN) spans immune thrombotic thrombocytopenic purpura, anti-phospholipid-associated microangiopathy, secondary endothelial injury, and complement-amplified/atypical hemolytic uremic syndrome (aHUS)-like phenotypes. The boundaries remain uncertain, and treatment evidence is dominated by selectively published cases. Methods: In this PROSPERO-registered systematic review (CRD420261409684), we searched PubMed, Embase, and Web of Science through to 17 March 2026, verified the source identity and eligibility, and performed a PubMed-only update through to 14 August 2026. We reconstructed patient-level reports by phenotype, competing mechanisms, complement-related evidence, treatment, and outcome. We included citable published abstracts when patient-level data were extractable but analyzed them as a lower-information stratum rather than as equivalent to full texts. Analyses were descriptive. We did not include China National Knowledge Infrastructure (CNKI) because no verifiable search record was available. One reviewer performed the screening, extraction, and appraisal. We report both as protocol deviations. Results: We included 56 sources describing 78 patients: in total, 39 full-text sources/61 patients and 17 published abstract sources/17 patients. There were 56 female patients (71.8%), and the median age was 24.5 years. Source-adjudicated microangiopathic hemolysis, thrombocytopenia, acute kidney injury/renal failure, strict TMA identified on kidney biopsy, and dialysis/renal replacement therapy (RRT) were present in 71 (91.0%), 74 (94.9%), 67 (85.9%), 42 (53.8%), and 46 (59.0%), respectively. Low C3/C4 levels were reported in 55 (70.5%), strict T2 complement evidence in 1 (1.3%), and index event terminal/tissue activation in 6 (7.7%). Complement inhibitors were reported in 60 (76.9%) and renal and hematologic improvements in 49 (62.8%) and 65 (83.3%), respectively. Certainty was very low, and treatment comparisons were not estimable. Conclusions: SLE/LN-associated TMA is heterogeneous, and complement may act as a driver, an amplifier, or an epiphenomenon. Case-based evidence supports rigorous mechanistic adjudication and biomarker-rich registries, but cannot establish incidence, prognosis, comparative efficacy, or universal treatment duration. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261409684 , identifier CRD420261409684.
SN - 1664-3224
ER -