Functional Characterization of Autoantibodies against Complement Component C3 in Patients with Lupus Nephritis

Vasilev, Vasil; Noé, Rémi; Dragon-Durey, Marie-Agnès; Chauvet, Sophie; Lazarov, Valentin; Deliyska, Boriana; Frémeaux‐Bacchi, Véronique; Dimitrov, Jordan D.; Roumenina, Lubka T.

doi:10.1074/jbc.m115.647008

Cited by 48 publications

(73 citation statements)

References 48 publications

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“…Therefore, further studies are needed in order to clarify if anti-FB and anti-C3b autoantibodies have a primary mechanistic role in the pathology of the lipodystrophy or if they rather secondarily arise as a consequence of the increase in circulating complement proteins produced due to unabated complement activation in the presence of C3NeF. A plausible possibility in line with the presence of C3NeF and low C3 levels in our BSS cohort is that these autoantibodies synergistically promote further C3 convertase stabilization and C3 consumption in serum, similarly to what has already been described by Vasilev and colleagues for anti-C3 and anti-C3b autoantibodies in patients with lupus nephritis [33,34].…”

Section: Discussionsupporting

confidence: 79%

Immunological features of patients affected by Barraquer-Simons syndrome

Corvillo

Ceccarini

Nozal

et al. 2020

Orphanet J Rare Dis

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Background: C3 hypocomplementemia and the presence of C3 nephritic factor (C3NeF), an autoantibody causing complement system over-activation, are common features among most patients affected by Barraquer-Simons syndrome (BSS), an acquired form of partial lipodystrophy. Moreover, BSS is frequently associated with autoimmune diseases. However, the relationship between complement system dysregulation and BSS remains to be fully elucidated. The aim of this study was to provide a comprehensive immunological analysis of the complement system status, autoantibody signatures and HLA profile in BSS. Thirteen subjects with BSS were recruited for the study. The circulating levels of complement components, C3, C4, Factor B (FB) and Properdin (P), as well as an extended autoantibody profile including autoantibodies targeting complement components and regulators were assessed in serum. Additionally, HLA genotyping was carried out using DNA extracted from peripheral blood mononuclear cells. Results: C3, C4 and FB levels were significantly reduced in patients with BSS as compared with healthy subjects. C3NeF was the most frequently found autoantibody (69.2% of cases), followed by anti-C3 (38.5%), and anti-P and anti-FB (30.8% each). Clinical data showed high prevalence of autoimmune diseases (38.5%), the majority of patients (61.5%) being positive for at least one of the autoantibodies tested. The HLA allele DRB1*11 was present in 54% of BSS patients, and the majority of them (31%) were positive for *11:03 (vs 1.3% allelic frequency in the general population). Conclusions: Our results confirmed the association between BSS, autoimmunity and C3 hypocomplementemia. Moreover, the finding of autoantibodies targeting complement system proteins points to complement dysregulation as a central pathological event in the development of BSS.

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Section: Discussionsupporting

confidence: 79%

Immunological features of patients affected by Barraquer-Simons syndrome

Corvillo

Ceccarini

Nozal

et al. 2020

Orphanet J Rare Dis

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“…The low C3 and C4 levels may result in a vicious cycle, because, in turn, accumulated IC activates and consumes complement through classical pathway [26]. Besides, autoantibodies such as anti-C1q could damage complement [27], and it has recently been reported that anti-C3 autoantibody levels correlated with disease activity [28]. Most SLE patients are complement deficient, and their immune system cannot clear IC effectively, increasing IC deposits to cause damage to organs or systems.…”

Section: Discussionmentioning

confidence: 99%

The Impact of T Cell Vaccination in Alleviating and Regulating Systemic Lupus Erythematosus Manifestation

Huang

Yang

et al. 2016

Journal of Immunology Research

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Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease identified by a plethora of production of autoantibodies. Autoreactive T cells may play an important role in the process. Attenuated T cell vaccination (TCV) has proven to benefit some autoimmune diseases by deleting or suppressing pathogenic T cells. However, clinical evidence for TCV in SLE is still limited. Therefore, this self-controlled study concentrates on the clinical effects of TCV on SLE patients. Methods. 16 patients were enrolled in the study; they accepted TCV regularly. SLEDAI, clinical symptoms, blood parameters including complements 3 and 4 levels, ANA, and anti-ds-DNA antibodies were tested. In addition, the side effects and drug usage were observed during the patients' treatment and follow-up. Results. Remissions in clinical symptoms such as facial rash, vasculitis, and proteinuria were noted in most patients. There are also evident reductions in SLEDAI, anti-ds-DNA antibodies, and GC dose and increases in C3 and C4 levels, with no pathogenic side effects during treatment and follow-up. Conclusions. T cell vaccination is helpful in alleviating and regulating systemic lupus erythematosus manifestation.

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“…In the serum samples positive for anti-C3 antibodies, the levels of C3 were significantly lower, compared with the negative samples. The authors speculate that anti-C3 antibodies enhance C3 convertase, resulting in a more efficient C3 cleavage [126]. In another study, antibodies against C3b, although less frequent than that against C1q, showed a higher specificity for LN, particularly for the prediction of renal flare [127].…”

Section: Lupus Nephritismentioning

confidence: 97%

“…To date, the autoantibodies against C3 and C3b have been reported in LN (Table 2) [126,127]. In the Bulgarian population, anti-C3 antibodies were present in 31% of patients (in 12 of total 39 individuals), and they correlated positively with anti-dsDNA antibodies levels, as well as with the severity of LN.…”

Section: Lupus Nephritismentioning

confidence: 99%

The role of the alternative pathway of complement activation in glomerular diseases

2018

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The complement system (CS) has recently been recognized as a bridge between innate and adaptive immunity that constitutes a very complex mechanism controlling the clearance of pathogens, cellular debris, and immune complexes. Out of three known pathways of complement activation, the alternative pathway (AP) plays a critical role in host defense by amplifying the complement response, independently of initiation pathway and continuously maintaining low-level activity in a process called 'thick-over.' A key molecule of the CS is C3, in which the AP is constantly activated. To prevent host cell destruction, a group of the AP regulators tightly controls this pathway of the CS activation. Acquired and genetic abnormalities of the CS may alter the delicate balance between enhancing and inhibiting the AP cascade. These can lead to the uncontrolled CS activation, inflammatory response, and subsequent tissue damage. Since complement components are locally produced and activated in the kidney, the abnormalities targeting the AP may cause glomerular injury. C3 glomerulopathy is a new entity, in which the AP dysregulation has been well established. However, recent studies indicate that the AP may also contribute to a wide range of kidney pathologies, including immune-complex-mediated glomerulonephritis (GN), pauci-immune GN, and primary membranous nephropathy (PMN). This article provides insight into current knowledge on the role of the AP in the pathogenesis of glomerular diseases, focusing mainly on various types of primary and secondary GN and PMN.

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Functional Characterization of Autoantibodies against Complement Component C3 in Patients with Lupus Nephritis

Cited by 48 publications

References 48 publications

Immunological features of patients affected by Barraquer-Simons syndrome

Immunological features of patients affected by Barraquer-Simons syndrome

The Impact of T Cell Vaccination in Alleviating and Regulating Systemic Lupus Erythematosus Manifestation

The role of the alternative pathway of complement activation in glomerular diseases

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