C1q: Its Functions within the Innate and Adaptive Immune Responses and its Role in Lupus Autoimmunity

Sontheimer, Richard D.; Racila, Emil; Racila, Doina

doi:10.1111/j.0022-202x.2005.23673.x

Cited by 90 publications

(59 citation statements)

References 54 publications

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“…Our findings indicate that anti-C1q antibodies are associated with SLE global activity but not specifically with active lupus nephritis. Although the main function of C1q is to clear ICs from tissues and self antigens generated during apoptosis (4), C1q has other biologic functions and could play roles as both facilitating and inhibiting/protective factors (30). As one example, Lood et al recently reported a novel function for C1q in the regulation of IC-induced production of interferon-␣ and other cytokines by plasmacytoid dendritic cells (31).…”

Section: Discussionmentioning

confidence: 99%

Anti‐C1q antibodies are associated with systemic lupus erythematosus global activity but not specifically with nephritis: A controlled study of 126 consecutive patients

Katsumata

Miyake

Kawaguchi

et al. 2011

Arthritis & Rheumatism

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Objective. Several studies have shown that antiC1q antibodies correlate with the occurrence and activity of nephritis in systemic lupus erythematosus (SLE). However, the significance of anti-C1q antibodies in SLE has not been fully characterized. The aim of this study was to investigate associations between anti-C1q antibodies and clinical and serologic parameters of SLE.Methods. An enzyme-linked immunosorbent assay kit was used to measure anti-C1q antibodies in the sera of 126 consecutive patients with active SLE who were admitted to our university hospital from 2007 through 2009. Sera obtained from patients with high titers of anti-C1q antibodies at the initial evaluation (n ‫؍‬ 20) were reevaluated following treatment. Control sera were obtained from patients with other autoimmune diseases and from normal healthy control subjects (n ‫؍‬ 20 in each group). Associations between anti-C1q antibodies and clinical and serologic parameters of SLE were statistically analyzed.Results. Anti-C1q antibodies were detected in the sera of 79 of 126 patients with SLE. The prevalence and titers of anti-C1q antibodies were significantly (P < 0.0001) higher in SLE patients than in patients with rheumatoid arthritis, patients with systemic sclerosis, and normal healthy control subjects. The prevalence and titers of anti-C1q antibodies were not significantly associated with active lupus nephritis (P ‫؍‬ 0.462 and P ‫؍‬ 0.366, respectively). Anti-C1q antibody titers were significantly correlated with SLE Disease Activity Index 2000 scores and the levels of anti-doublestranded DNA antibodies, C3, C4, CH50, and C1q (P < 0.0001 for all comparisons). Moreover, anti-C1q antibody titers significantly decreased as clinical disease was ameliorated following treatment (P ‫؍‬ 0.00097).Conclusion. These findings indicate that anti-C1q antibodies are associated with SLE global activity but not specifically with active lupus nephritis.

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Section: Discussionmentioning

confidence: 99%

Anti‐C1q antibodies are associated with systemic lupus erythematosus global activity but not specifically with nephritis: A controlled study of 126 consecutive patients

Katsumata

Miyake

Kawaguchi

et al. 2011

Arthritis & Rheumatism

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“…Patients with C1q deficiency can develop lupus with high penetrance (18). It has been reported that more than 90% of individuals with complete congenital deficiency of C1q can develop early-onset photosensitive SLE (14). The presence of anti-C1q has been also strongly correlated with hypocomplementemia, disease activity and renal involvement in SLE patients (20).…”

Section: Discussionmentioning

confidence: 99%

“…The classical pathway of complement activation is characterized by the binding of C1q to immune complexes (13). C1q is a recognition component in the classical pathway, and it can help solubilize immune complexes and aid in the clearance of apoptotic debris (14). The gene coding region for C1q is localized on chromosome 1p34-36 and consists of three genes, C1qA, C1qB and C1qC (15).…”

Section: Introductionmentioning

confidence: 99%

Association between C1q gene polymorphisms and autoimmune thyroid diseases

Yao

et al. 2017

Arch. Endocrinol. Metab.

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Objective: In the present study, we aimed to assess the associations of C1q gene polymorphisms with autoimmune thyroid diseases (AITD) susceptibility. Subjects and methods: A set of 1,003 AITD patients (661 with Graves' disease and 342 with Hashimoto's thyroiditis) and 880 ethnicallyand geographically-matched controls from Chinese Han population were included. Five common single nucleotide polymorphisms (SNPs) (rs294185, rs292001, rs682658, rs665691 and rs294179) in C1q gene locus were genotyped. Frequencies of genotypes and alleles were compared between patients and controls, and haplotype analysis was also performed. Results: There was no statistically significant difference between AITD patients and controls in the frequencies of alleles of rs294185 (P = 0.41), rs292001 (P = 0.71), rs682658 (P = 0.68), rs665691 (P = 0.68) and rs294179 (P = 0.69). There was also no statistically significant difference between AITD patients and controls in the frequencies of genotypes of rs294185 (P = 0.72), rs292001 (P = 0.89), rs682658 (P = 0.83), rs665691 (P = 0.90) and rs294179 (P = 0.43). Stratified analyses showed that none of those five SNPs in C1q gene were associated with Graves' disease or Hashimoto's thyroiditis (all P values > 0.05). Haplotype analysis revealed that there were no obvious genetic associations of C1q gene polymorphisms with AITD susceptibility. Conclusions: We, for the first time, identified the associations between C1q gene SNPs and AITD, and our findings suggested that five common SNPs in C1q gene were not associated with AITD susceptibility in Chinese Han population. Arch Endocrinol Metab. 2017;61(3):337-42.

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“…C1q is mostly produced outside the liver by monocytes, macrophages, fibroblasts, dendritic cells and epithelial cells [4]. Therefore the functions of C1q are related to its ability to bind to different molecules and receptors.…”

Section: C1qmentioning

confidence: 99%

“…Therefore the functions of C1q are related to its ability to bind to different molecules and receptors. It plays a key role in the activation of the complement cascade through the classic pathway: its binding to the Fc region of Ig activates C1r and C1s, leading to C4 cleavage by an enzymatic reaction [4]. C1q acts as a bridging molecule between debris from cellular apoptosis (apoptotic bodies) and macrophages.…”

Section: C1qmentioning

confidence: 99%

Protective molecules and their cognate antibodies: new players in autoimmunity

Zen

Bassi

Campana

et al. 2010

Autoimmun Highlights

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Impairment of the clearance of apoptotic material seems to contribute to autoantigen exposure, which can initiate or maintain an autoimmune response in predisposed individuals. Complement component C1q, Creactive protein (CRP), serum amyloid P (SAP), mannose-binding lectin (MBL), apolipoprotein A-1 (Apo A-1) and long pentraxin 3 (PTX3) are molecules involved in the removal of apoptotic bodies and pathogens, and in other antiinflammatory pathways. For this reason they have been called “protective” molecules. C1q has a key role in the activation of the complement cascade and acts as a bridging molecule between apoptotic bodies and macrophages favouring phagocytosis. In addition to other functions, CRP, SAP and MBL bind to the surface of numerous pathogens as well as cellular debris and activate the complement cascade, thus stimulating their clearance by immune cells. The role of PTX3 is more controversial. In fact, PTX also promotes the clearance of microorganisms, but the activation of the complement cascade through C1q and removal of apoptotic material can be either stimulated or inhibited by this molecule. Antibodies against protective molecules have been recently reported in systemic lupus erythematosus and other autoimmune rheumatic diseases. Some of them seem to be pathogenetic and others protective. Thus, protective molecules and their cognate antibodies may constitute a regulatory network involved in autoimmunity. Dysregulation of this system might contribute to the development of autoimmune diseases in predisposed individuals.

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C1q: Its Functions within the Innate and Adaptive Immune Responses and its Role in Lupus Autoimmunity

Cited by 90 publications

References 54 publications

Anti‐C1q antibodies are associated with systemic lupus erythematosus global activity but not specifically with nephritis: A controlled study of 126 consecutive patients

Anti‐C1q antibodies are associated with systemic lupus erythematosus global activity but not specifically with nephritis: A controlled study of 126 consecutive patients

Association between C1q gene polymorphisms and autoimmune thyroid diseases

Protective molecules and their cognate antibodies: new players in autoimmunity

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