Complement activation by (auto-) antibodies

Daha, Nina A.; Banda, Nirmal K.; Roos, Anja; Beurskens, Frank J.; Bakker, Joost M.; Daha, Mohamed R.; Trouw, Leendert A.

doi:10.1016/j.molimm.2011.04.024

Cited by 125 publications

(106 citation statements)

References 147 publications

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“…Immune complexes, formed, for example, by anti-citrullinated protein antibodies (ACPA), can trigger the classical pathway [39]. However, this would occur after the induction of such antibodies [40,41], which would put genetic variants of C1q at the effector-phase of RA rather than at the onset of RA. We have divided the patient group on the basis of their ACPA status and found the effect of C1q genetic variants in both strata, although the P-values were stronger in the larger ACPA-positive group (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Genetic variants in the region of the C1q genes are associated with rheumatoid arthritis

Trouw

Daha

Kurreeman

et al. 2013

Clinical and Experimental Immunology

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SummaryRodent models for arthritis implicate a role for complement in disease development and progression. In humans, complement deposition has been observed in inflamed synovia of rheumatoid arthritis (RA) patients. In this study we analysed whether genetic variants of complement component C1q predispose to RA. We genotyped single nucleotide polymorphisms (SNPs) in and around the C1q genes, C1qA, C1qB and C1qC, in a Dutch set of 845 RA cases and 1046 controls. Replication was sought in a sample set from North America (868 cases/1193 controls), and a meta-analysis was performed in a combined samples set of 8000 cases and 23 262 controls of European descent. We determined C1q serum levels in relation to C1q genotypes. In the discovery phase, five of the 13 SNPs tested in the C1q genes showed a significant association with RA. Additional analysis of the genomic area around the C1q genes revealed that the strongest associating SNPs were confined to the C1q locus. Within the C1q locus we observed no additional signal independent of the strongest associating SNP, rs292001 [odds ratio (OR) = 0·72 (0·58-0·88), P = 0·0006]. The variants of this SNP were associated with different C1q serum levels in healthy controls (P = 0·006). Interestingly, this SNP was also associated significantly in genome-wide association studies (GWAS) from the North American Rheumatoid Arthritis Consortium study, confirming the association with RA [OR = 0·83 (0·69-1·00), P = 0·043]. Combined analysis, including integrated data from six GWAS studies, provides support for the genetic association. Genetic variants in C1q are correlated with C1q levels and may be a risk for the development of RA.

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Section: Discussionmentioning

confidence: 99%

Genetic variants in the region of the C1q genes are associated with rheumatoid arthritis

Trouw

Daha

Kurreeman

et al. 2013

Clinical and Experimental Immunology

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“…Interestingly, in the human situation, RA-associated antibodies, ACPA, also display a strong capacity to activate AP [16]. These data indicate collectively that arthritogenic/arthritisassociated antibodies use the AP to activate complement [17]. Complement deposits, which also contain AP components, can be found in the inflamed joint [18].…”

Section: Introductionmentioning

confidence: 99%

The major risk alleles of age-related macular degeneration (AMD) in CFH do not play a major role in rheumatoid arthritis (RA)

Trouw¹,

Böhringer

Daha³

et al. 2011

Clinical and Experimental Immunology

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SummaryBecause activation of the alternative pathway (AP) of the complement system is an important aspect of both age-related macular degeneration (AMD) and rheumatoid arthritis (RA), we wished to address the question whether genetic risk factors of the AP inhibitor complement factor H (CFH) for AMD would also be risk factors for RA. For this purpose we genotyped single nucleotide polymorphisms (SNPs) in a Dutch set of RA patients and controls. Similarly, a meta-analysis using a Spanish cohort of RA as well as six large genome-wide association studies (GWAS) studies was performed. For these SNPs we analysed more than 6000 patients and 20 000 controls. The CFH variants, I62V, Y402H, IVS1 and IVS10, known to associate strongly with AMD, did not show a significant association with the risk of developing RA despite a strong statistical power to detect such differences. In conclusion, the major risk alleles of AMD in CFH do not have a similar effect on developing RA.

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“…Pathogen-specific antibodies activate the classical complement pathway (10). Bacterial surface glycopolymers are also recognized by a variety of pattern recognition molecules, including mannose-binding lectin (MBL) (11,12).…”

mentioning

confidence: 99%

“…The immune complexes also induce phagocytosis via cell surface Fc␥ receptors (Fc␥Rs). Because S. aureus is a Gram-positive bacterium with a thick peptidoglycan layer, many reports have suggested that serum antibody-mediated opsonophagocytosis is necessary to combat pathogenic S. aureus infection (10,15). Additionally, MBL deficiency in mice caused susceptibility to S. aureus infection (16).…”

mentioning

confidence: 99%

Glycoepitopes of Staphylococcal Wall Teichoic Acid Govern Complement-mediated Opsonophagocytosis via Human Serum Antibody and Mannose-binding Lectin

Kurokawa

Jung

et al. 2013

Journal of Biological Chemistry

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Background:The exact staphylococcal antigenic determinants of anti-staphylococcal IgG and mannose-binding lectin (MBL) have not been determined. Results:The antigenic epitopes of the staphylococcal wall teichoic acid (WTA) for serum IgG and MBL are O-N-acetyl-Dglucosamine residues. Conclusion: The sugar moiety of WTA is an important molecular determinant in host responses to S. aureus. Significance: The results provide new insights into the host-pathogen interaction.

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Complement activation by (auto-) antibodies

Cited by 125 publications

References 147 publications

Genetic variants in the region of the C1q genes are associated with rheumatoid arthritis

Genetic variants in the region of the C1q genes are associated with rheumatoid arthritis

The major risk alleles of age-related macular degeneration (AMD) in CFH do not play a major role in rheumatoid arthritis (RA)

Glycoepitopes of Staphylococcal Wall Teichoic Acid Govern Complement-mediated Opsonophagocytosis via Human Serum Antibody and Mannose-binding Lectin

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