C4d as a Screening Tool and an Independent Predictor of Clinical Outcomes in Lupus Nephritis and IgA Nephropathy

Yang, Xiaoqian; Yuan, Yanhong; Shao, Xinghua; Pang, Huihua; Che, Xiajing; Cao, Liou; Zhang, Minfang; Xu, Yao; Ni, Zhaohui; Chen, Qi; Wang, Qin; Mou, Shan

doi:10.3389/fmed.2022.832998

Cited by 6 publications

(6 citation statements)

References 42 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…, 31 2020 C3, C4, C4d, C1q, C5b9, MBL, MASP1/3, MASP2, properdin, factor B Japan Adult 132 IF 52 55 61.1 (9.7–162) 1.3 (0.04–7.8) Yang et al. , 32 2022 C4d China Adult 120 IHC 32 47 85.8 (60.3–110.7) 1.0 (0.8–3.5) Baek et al. , 33 2018 C4d Korea Pediatric 56 IHC 12.1 59 109.5 ± 32.4 0.5 (0.2–2.0) Wen et al.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Systematic Review of the Link Between Oxford MEST-C Classification and Complement Activation in IgA Nephropathy

Ștefan,

Alamartine,

Mariat

et al. 2024

Kidney International Reports

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

“…, 31 2020 Associated with T1-2 class a Yang et al. , 32 2022 Associated with M1 class a Baek et al. , 33 2018 Positive correlation with C1-2 class c Wen et al.…”

Section: Resultsmentioning

confidence: 99%

Systematic Review of the Link Between Oxford MEST-C Classification and Complement Activation in IgA Nephropathy

Ștefan,

Alamartine,

Mariat

et al. 2024

Kidney International Reports

View full text Add to dashboard Cite

“…In contrast, C4d is derived from the cleavage of C4 and hence indicates both classical and lectin pathway but not alternative pathway activation. Besides that, many C3d and C4d assays are widely used in routine diagnostics and available commercially, especially investigation of C4d is mainly used for immunostaining in (kidney) biopsies (19)(20)(21). Although C4d is perfectly able to distinguish between CP/LP and AP activation, no well-established markers to measure early classical and early lectin pathway activation are available.…”

Section: Introductionmentioning

confidence: 99%

Distinction of early complement classical and lectin pathway activation via quantification of C1s/C1-INH and MASP-1/C1-INH complexes using novel ELISAs

Hurler¹,

Toonen²,

Kajdácsi³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

The most commonly used markers to assess complement activation are split products that are produced through activation of all three pathways and are located downstream of C3. In contrast, C4d derives from the cleavage of C4 and indicates either classical (CP) or lectin pathway (LP) activation. Although C4d is perfectly able to distinguish between CP/LP and alternative pathway (AP) activation, no well-established markers are available to differentiate between early CP and LP activation. Active enzymes of both pathways (C1s/C1r for the CP, MASP-1/MASP-2 for the LP) are regulated by C1 esterase inhibitor (C1-INH) through the formation of covalent complexes. Aim of this study was to develop validated immunoassays detecting C1s/C1-INH and MASP-1/C1-INH complex levels. Measurement of the complexes reveals information about the involvement of the respective pathways in complement-mediated diseases. Two sandwich ELISAs detecting C1s/C1-INH and MASP-1/C1-INH complex were developed and tested thoroughly, and it was investigated whether C1s/C1-INH and MASP-1/C1-INH complexes could serve as markers for either early CP or LP activation. In addition, a reference range for these complexes in healthy adults was defined, and the assays were clinically validated utilizing samples of 414 COVID-19 patients and 96 healthy controls. The immunoassays can reliably measure C1s/C1-INH and MASP-1/C1-INH complex concentrations in EDTA plasma from healthy and diseased individuals. Both complex levels are increased in serum when activated with zymosan, making them suitable markers for early classical and early lectin pathway activation. Furthermore, measurements of C1-INH complexes in 96 healthy adults showed normally distributed C1s/C1-INH complex levels with a physiological concentration of 1846 ± 1060 ng/mL (mean ± 2SD) and right-skewed distribution of MASP-1/C1-INH complex levels with a median concentration of 36.9 (13.18 - 87.89) ng/mL (2.5-97.5 percentile range), while levels of both complexes were increased in COVID-19 patients (p<0.0001). The newly developed assays measure C1-INH complex levels in an accurate way. C1s/C1-INH and MASP-1/C1-INH complexes are suitable markers to assess early classical and lectin pathway activation. An initial reference range was set and first studies showed that these markers have added value for investigating and unraveling complement activation in human disease.

show abstract

“…In addition to the glomerulus, PTC C4d-positive staining was also observed in renal biopsies from LN patients. 26–28 However, there are differences in the PTC C4d detection frequencies in LN patients. 16,20,26,27 Li et al 26 and Drachenber et al 16 recorded similar low frequencies of PTC C4d detection: 6.8% and 8.8%, respectively, by indirect immunofluorescence on frozen tissue sections.…”

Section: C4d Staining In Renal Biopsies From Ln Patientsmentioning

confidence: 99%

Complement C4d as a biomarker for systemic lupus erythematosus and lupus nephritis

Qin,

Wang,

Wang

et al. 2024

Lupus

View full text Add to dashboard Cite

Background: Increasing studies in the last decade have led to the widespread understanding that C4d, a split product of complement component 4 (C4), is a potential biomarker for systemic lupus erythematosus (SLE) and lupus nephritis (LN). Purpose: The aim of this review is to summarize the highlights of studies investigating the use of C4d as a biomarker for diagnosing and monitoring SLE and LN patients. Data collection: we searched PubMed/Medline and Wanfang databases using the terms “C4d and systemic lupus erythematosus”, “C4d and lupus nephritis”, and “Complement C4d”. Results: The deposition of C4d on circulating blood cells has been shown in several clinical studies to be a potential diagnostic marker that can be used to monitor patients with SLE. In addition, C4d deposits on circulating blood cells may be a helpful diagnostic marker for LN, one of the most severe complications of SLE. Meanwhile, studies utilizing renal biopsy specimens have indicated that C4d deposition in the renal peritubular capillaries of LN patients may predict more severe LN or a worse patient prognosis. Generally, a high plasma C4d level and a high plasma C4d/C4 ratio may also be promising indicators that can be used to monitor patients with SLE and LN. Conclusions: C4d detection may be a novel strategy for further clinical prediction and therapy.

show abstract

C4d as a Screening Tool and an Independent Predictor of Clinical Outcomes in Lupus Nephritis and IgA Nephropathy

Cited by 6 publications

References 42 publications

Systematic Review of the Link Between Oxford MEST-C Classification and Complement Activation in IgA Nephropathy

Systematic Review of the Link Between Oxford MEST-C Classification and Complement Activation in IgA Nephropathy

Distinction of early complement classical and lectin pathway activation via quantification of C1s/C1-INH and MASP-1/C1-INH complexes using novel ELISAs

Complement C4d as a biomarker for systemic lupus erythematosus and lupus nephritis

Contact Info

Product

Resources

About