Clinical correlations with serum C1q levels in patients with rheumatoid arthritis

Olsen, Nancy J.; Ho, E. T. F.; Барац, Л. С.

doi:10.1002/art.1780340209

Cited by 12 publications

(6 citation statements)

References 16 publications

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“…C3b was also present on the cartilage surface of RA patients; thus, this study clearly showed that C1s can activate the downstream complement cascade thereby causing irreversible damage. It has also been shown that the level of C1q in serum correlates with clinical disease activity (CDA) in RA patients ( 144 – 146 ). In mouse model of RA, C3b gets deposited first on the surface of cartilage vs. synovium and increased rapidly from 4 to 120 h (Figure 2 ).…”

Section: Initiation Of Rheumatoid Arthritismentioning

confidence: 99%

Complement in the Initiation and Evolution of Rheumatoid Arthritis

2018

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The complement system is a major component of the immune system and plays a central role in many protective immune processes, including circulating immune complex processing and clearance, recognition of foreign antigens, modulation of humoral and cellular immunity, removal of apoptotic and dead cells, and engagement of injury resolving and tissue regeneration processes. In stark contrast to these beneficial roles, however, inadequately controlled complement activation underlies the pathogenesis of human inflammatory and autoimmune diseases, including rheumatoid arthritis (RA) where the cartilage, bone, and synovium are targeted. Recent studies of this disease have demonstrated that the autoimmune response evolves over time in an asymptomatic preclinical phase that is associated with mucosal inflammation. Notably, experimental models of this disease have demonstrated that each of the three major complement activation pathways plays an important role in recognition of injured joint tissue, although the lectin and amplification pathways exhibit particularly impactful roles in the initiation and amplification of damage. Herein, we review the complement system and focus on its multi-factorial role in human patients with RA and experimental murine models. This understanding will be important to the successful integration of the emerging complement therapeutics pipeline into clinical care for patients with RA.

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Section: Initiation Of Rheumatoid Arthritismentioning

confidence: 99%

Complement in the Initiation and Evolution of Rheumatoid Arthritis

2018

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“…From the viewpoint of sensitivity, blood levels of C1q can be quantified, demonstrating its suitability for minimally invasive blood tests. However, from the viewpoint of specificity, blood levels of C1q are increased in rheumatoid arthritis [ 21 ] and sarcopenia [ 22 ]. Furthermore, considering that CKD is a consequence of numerous and diverse primary diseases with complicated underlying pathology, it will be difficult to diagnose CKD solely on the basis of blood levels of C1q.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers of chronic kidney disease among kidney-derived proteins

et al. 2022

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Background Chronic kidney disease (CKD) has few objective symptoms, and it is difficult to make an early diagnosis by using existing methods. Therefore, new biomarkers enabling diagnosis of renal dysfunction at an early stage need to be developed. Here, we searched for new biomarkers of CKD by focusing on kidney-derived proteins that could sensitively reflect that organ’s disease state. Methods To identify candidate marker proteins, we performed a proteomics analysis on renal influx and efflux blood collected from the same individual. Results Proteomics analysis revealed 662 proteins in influx blood and 809 in efflux. From these identified proteins, we selected complement C1q as a candidate; the plasma C1q level was significantly elevated in the renal efflux of donors. Moreover, the plasma concentration of C1q in a mouse model of diabetic nephropathy was significantly increased, in association with increases in blood glucose concentration and urinary protein content. Importantly, we demonstrated that the tendency of C1q to increase in the plasma of CKD patients was correlated with a decrease in their estimated glomerular filtration rate. Conclusion Overall, our results indicate that our approach of focusing on kidney-derived proteins is useful for identifying new CKD biomarkers and that C1q has potential as a biomarker of renal function.

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“…We also observed that the consumption of serum C3 was reduced in CIA mice treated with anti-CII Fabs, which lacks the Fc portion as the binding site of complements; furthermore, the in vitro complement inhibition assay showed that ICs-mediated activation of C3 complement was suppressed by anti-CII Fabs. It has been reported that the provoked level of C3a in the serum of RA patients is correlated with laboratory and clinical manifestations of RA [4,26], whereas the reduced levels of C3 are comparable to those of healthy subjects [27]. The activated protein of C3a is a potent mediator involved in inflammatory responses, including alteration of vascular permeability, opsonization for inflammatory leukocytes and activation of release pro-inflammatory cytokines [28]; moreover, murine CIA suppressed by the C3 convertase inhibitor has been reported [29].…”

Section: Discussionmentioning

confidence: 99%

Suppression of Collagen-Induced Arthritis in Mice by Anti-Collagen Antibody Fab Fragments

Yoshino¹,

Maktrirat²,

Mizutani³

2014

J Arthritis

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Fabs fragments (Fabs) maintain binding ability to specific antigens, but lack the binding site for complements and for receptors on leukocytes that play a crucial role in Rheumatoid Arthritis (RA). In the present study, we investigated whether type II Collagen (CII)-Induced Arthritis (CIA) in mice was suppressed by anti-CII Fabs prepared by papain digestion of anti-CII antibodies. CIA was induced in DBA/1J mice by immunization with chicken CII and completes Freund's adjuvant. To investigate the effect of anti-CII Fabs on the CIA model, mice were injected intraperitoneally with anti-CII Fabs 1 day before the first immunization. As a result, CIA was markedly inhibited by anti-CII Fabs; furthermore, the histological features of anti-CII Fabs-untreated mice included severe hyperplatic synnovium, cartilage and joint destruction, and leukocytic infiltration, whereas animals given anti-CII Fabs showed significant reduction of these histological changes. Additionally, antigen-specific suppression of CIA by anti-CII Fabs was related to the reduced levels of complement C3a in serum. Meanwhile, in vitro studies revealed that anti-CII Fabs significantly blocked the binding of intact anti-CII antibodies and also decreased complement activation. Collectively, the development of CIA was suppressed by anti-CII Fabs, which prevented the binding of anti-CII antibodies to antigen followed by the inhibition of complement activation, suggesting that autoimmune arthritic diseases such as RA may be specifically treated with pathogenic antibody Fabs.

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Clinical correlations with serum C1q levels in patients with rheumatoid arthritis

Cited by 12 publications

References 16 publications

Complement in the Initiation and Evolution of Rheumatoid Arthritis

Complement in the Initiation and Evolution of Rheumatoid Arthritis

Identification of biomarkers of chronic kidney disease among kidney-derived proteins

Suppression of Collagen-Induced Arthritis in Mice by Anti-Collagen Antibody Fab Fragments

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