Cross, M. et al. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann. Rheumatol. Dis. 73, 1316–1322 (2014).
Google Scholar
Smolen, J. S. et al. Rheumatoid arthritis. Nat. Rev. Dis. Primers. 4, 18001 (2018).
Google Scholar
Fallon, E. A. et al. Prevalence of diagnosed Arthritis – United States, 2019–2021. MMWR Morb Mortal. Wkly. Rep. 72, 1101–1107 (2023).
Google Scholar
Singh, D. K. et al. Use of rheumatologic testing in patients who eventually receive a diagnosis of rheumatoid arthritis. South Med. J. 112, 535–538 (2019).
Google Scholar
Prevoo, M. L., van ‘t Hof, M. A., Kuper, H. H., van Leeuwen, M. A. & van de Putte, L. B. and P. L. van Riel. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheumatol 38: 44–48. (1995).
Sengul, I., Akcay-Yalbuzdag, S., Ince, B., Goksel-Karatepe, A. & Kaya, T. Comparison of the DAS28-CRP and DAS28-ESR in patients with rheumatoid arthritis. Int. J. Rheumatol. Dis. 18, 640–645 (2015).
Google Scholar
Nielen, M. M. et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheumatol. 50, 380–386 (2004).
Google Scholar
Ballanti, E. et al. Complement and autoimmunity. Immunol. Res. 56, 477–491 (2013).
Google Scholar
Holers, V. M. & Banda, N. K. Complement in the initiation and evolution of rheumatoid arthritis. Front. Immunol. 9, 1057 (2018).
Google Scholar
Banda, N. K. et al. Analysis of complement gene expression, clinical associations, and biodistribution of complement proteins in the synovium of early rheumatoid arthritis patients reveals unique pathophysiologic features. J. Immunol. 208, 2482–2496 (2022).
Google Scholar
Markiewski, M. M. & Lambris, J. D. The role of complement in inflammatory diseases from behind the scenes into the spotlight. Am. J. Pathol. 171, 715–727 (2007).
Google Scholar
Merle, N. S., Noe, R., Halbwachs-Mecarelli, L., Fremeaux-Bacchi, V. & Roumenina, L. T. Complement system part II: role in immunity. Front. Immunol. 6, 257 (2015).
Google Scholar
Morgan, B. P., Marchbank, K. J., Longhi, M. P., Harris, C. L. & Gallimore, A. M. Complement: central to innate immunity and bridging to adaptive responses. Immunol. Lett. 97, 171–179 (2005).
Google Scholar
Morgan, B. P., Boyd, C. & Bubeck, D. Molecular cell biology of complement membrane attack. Semin Cell. Dev. Biol. 72, 124–132 (2017).
Google Scholar
Zwarthoff, S. A. et al. Functional characterization of alternative and classical pathway C3/C5 convertase activity and Inhibition using purified models. Front. Immunol. 9, 1691 (2018).
Google Scholar
Foley, J. H. et al. Interplay between fibrinolysis and complement: plasmin cleavage of iC3b modulates immune responses. J. Thromb. Haemost. 13, 610–618 (2015).
Google Scholar
Nilsson, U. R., Funke, L., Nilsson, B. & Ekdahl, K. N. Two conformational forms of target-bound iC3b that distinctively bind complement receptors 1 and 2 and two specific monoclonal antibodies. Ups J. Med. Sci. 116, 26–33 (2011).
Google Scholar
Jozsi, M. & Zipfel, P. F. Factor H family proteins and human diseases. Trends Immunol. 29, 380–387 (2008).
Google Scholar
Zipfel, P. F. et al. Factor H family proteins: on complement, microbes and human diseases. Biochem. Soc. Trans. 30, 971–978 (2002).
Google Scholar
Zipfel, P. F. & Skerka, C. Complement factor H and related proteins: an expanding family of complement-regulatory proteins? Immunol. Today. 15, 121–126 (1994).
Google Scholar
Karpati, E. et al. Complement factor H family proteins modulate monocyte and neutrophil granulocyte functions. Front. Immunol. 12, 660852 (2021).
Google Scholar
Karpati, E. et al. Interaction of the factor H family proteins FHR-1 and FHR-5 with DNA and dead cells: implications for the regulation of complement activation and opsonization. Front. Immunol. 11, 1297 (2020).
Google Scholar
Sandor, N. et al. The human factor H protein family—an update. Front. Immunol. 15, 1135490 (2024).
Google Scholar
Mehta, G., Ferreira, V. P., Skerka, C., Zipfel, P. F. & Banda, N. K. New insights into disease-specific absence of complement factor H related protein C in mouse models of spontaneous autoimmune diseases. Mol. Immunol. 62, 235–248 (2014).
Google Scholar
Castell, J. V. et al. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes. FEBS Lett. 242, 237–239 (1989).
Google Scholar
Sproston, N. R. & Ashworth, J. J. Role of C-reactive protein at sites of inflammation and infection. Front. Immunol. 9, 754 (2018).
Google Scholar
Pope, J. E. & Choy, E. H. C-reactive protein and implications in rheumatoid arthritis and associated comorbidities. Semin Arthritis Rheumatol. 51, 219–229 (2021).
Google Scholar
Orr, C. K. et al. The utility and limitations of CRP, ESR and DAS28-CRP in appraising disease activity in rheumatoid arthritis. Front. Med. (Lausanne). 5, 185 (2018).
Google Scholar
Mihlan, M. et al. Human complement factor H-related protein 4 binds and recruits native pentameric C-reactive protein to necrotic cells. Mol. Immunol. 46, 335–344 (2009).
Google Scholar
Hebecker, M. et al. Molecular basis of C-reactive protein binding and modulation of complement activation by factor H-related protein 4. Mol. Immunol. 47, 1347–1355 (2010).
Google Scholar
McRae, J. L. et al. Human factor H-related protein 5 has cofactor activity, inhibits C3 convertase activity, binds heparin and C-reactive protein, and associates with lipoprotein. J. Immunol. 174, 6250–6256 (2005).
Google Scholar
Lewis, M. J. et al. Molecular portraits of early rheumatoid arthritis identify clinical and treatment response phenotypes. Cell. Rep. 28, 2455–2470e2455 (2019).
Google Scholar
Rivellese, F. et al. Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials. Lancet Rheumatol. 5, e648–e659 (2023).
Google Scholar
Love, M. I., Huber, W. & Anders, S. Moderated Estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Google Scholar
Holers, V. M. et al. Potential causal role of synovial complement system activation in the development of post-traumatic osteoarthritis after anterior cruciate ligament injury or meniscus tear. Front. Immunol. 14, 1146563 (2023).
Google Scholar
Holers, V. M. et al. Decay-accelerating factor differentially associates with complement-mediated damage in synovium after meniscus tear as compared to anterior cruciate ligament injury. Immune Netw. 24, e17 (2024).
Google Scholar
van der Heijde, D. How to read radiographs according to the Sharp/van der Heijde method. J. Rheumatol. 27, 261–263 (2000).
Google Scholar
Genant, H. K. et al. Assessment of rheumatoid arthritis using a modified scoring method on digitized and original radiographs. Arthritis Rheumatol. 41, 1583–1590 (1998).
Google Scholar
Lewis, M. J. Predicting best treatment in rheumatoid arthritis. Semin Arthritis Rheumatol. 64S, 152329 (2024).
Google Scholar
Humby, F. et al. and R. R. c. Group. 2021. Rituximab versus Tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial. Lancet 397: 305–317 .
Donlin, L. T. et al. Methods for high-dimensional analysis of cells dissociated from cryopreserved synovial tissue. Arthritis Res. Ther. 20: 139. (2018).
Jones, M. B. IgG and leukocytes: targets of Immunomodulatory alpha2,6 Sialic acids. Cell. Immunol. 333, 58–64 (2018).
Google Scholar
Wang, Y. et al. Loss of alpha2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in arthritis. Nat. Commun. 12, 2343 (2021).
Google Scholar
Kissel, T., Toes, R. E. M., Huizinga, T. W. J. & Wuhrer, M. Glycobiology of rheumatic diseases. Nat. Rev. Rheumatol. 19, 28–43 (2023).
Google Scholar
Eberhardt, H. U. et al. Human factor H-related protein 2 (CFHR2) regulates complement activation. PLoS One. 8, e78617 (2013).
Google Scholar
Merinero, M. et al. Molecular bases for the association of FHR-1 with atypical hemolytic uremic syndrome and other diseases. Blood 137, 3484–3494 (2021).
Google Scholar
Cserhalmi, M., Papp, A., Brandus, B., Uzonyi, B. & Jozsi, M. Regulation of regulators: role of the complement factor H-related proteins. Semin Immunol. 45, 101341 (2019).
Google Scholar
Medjeral-Thomas, N. & Pickering, M. C. The complement factor H-related proteins. Immunol. Rev. 274, 191–201 (2016).
Google Scholar
Skerka, C., Chen, Q., Fremeaux-Bacchi, V. & Roumenina, L. T. Complement factor H related proteins (CFHRs). Mol. Immunol. 56, 170–180 (2013).
Google Scholar
Leffler, J. et al. Annexin-II, DNA, and histones serve as factor H ligands on the surface of apoptotic cells. J. Biol. Chem. 285, 3766–3776 (2010).
Google Scholar
Borza, D. B. Glomerular basement membrane Heparan sulfate in health and disease: a regulator of local complement activation. Matrix Biol. 57–58, 299–310 (2017).
Google Scholar
Gyapon-Quast, F. et al. Defining the glycosaminoglycan interactions of complement factor H-related protein 5. J. Immunol. 207, 534–541 (2021).
Google Scholar
Mahajan, S. et al. Local complement factor H protects kidney endothelial cell structure and function. Kidney Int. 100, 824–836 (2021).
Google Scholar
Jia, Y. et al. Complement factor H attenuates TNF-alpha-induced inflammation by upregulating EIF3C in rheumatoid arthritis. J. Transl Med. 21, 846 (2023).
Google Scholar
Jiang Li, K. W. et al. Hoh and. Complement factor H in molecular regulation of angiogenesis. Med. Rev. 4, 452–466. https://doi.org/10.1515/mr-2023-0048 (2024).
Ju, Liu & Hoh, J. Loss of complement factor H in plasma increases endothelial cell migration. J. Cancer. 8 (12), 2184–2190 (2017).
Google Scholar
Zhang, F. et al. Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes. Nature 623: 616–624. (2023).
Molins, B. et al. Complement factor H binding of monomeric C-reactive protein downregulates proinflammatory activity and is impaired with at risk polymorphic CFH variants. Sci. Rep. 6, 22889 (2016).
Google Scholar
Seddon, J. M., Gensler, G., Klein, M. L. & Milton, R. C. C-reactive protein and homocysteine are associated with dietary and behavioral risk factors for age-related macular degeneration. Nutrition 22, 441–443 (2006).
Google Scholar
Seddon, J. M., George, S., Rosner, B. & Rifai, N. Progression of age-related macular degeneration: prospective assessment of C-reactive protein, Interleukin 6, and other cardiovascular biomarkers. Arch. Ophthalmol. 123, 774–782 (2005).
Google Scholar
Vine, A. K., Stader, J., Branham, K., Musch, D. C. & Swaroop, A. Biomarkers of cardiovascular disease as risk factors for age-related macular degeneration. Ophthalmology 112, 2076–2080 (2005).
Google Scholar
Lee, J. H. et al. Proteomic analysis of human synovial fluid reveals potential diagnostic biomarkers for ankylosing spondylitis. Clin. Proteom. 17, 20 (2020).
Google Scholar
Lee, J. H. et al. The complement factor H-related protein-5 (CFHR5) exacerbates pathological bone formation in ankylosing spondylitis. J. Mol. Med. (Berl). 102, 571–583 (2024).
Google Scholar
Linos, A., Worthington, J. W., O’Fallon, W. M. & Kurland, L. T. The epidemiology of rheumatoid arthritis in Rochester, Minnesota: a study of incidence, prevalence, and mortality. Am. J. Epidemiol. 111, 87–98 (1980).
Google Scholar
Halldorsdottir, H. D., Jonsson, T., Thorsteinsson, J. & Valdimarsson, H. A prospective study on the incidence of rheumatoid arthritis among people with persistent increase of rheumatoid factor. Ann. Rheumatol. Dis. 59, 149–151 (2000).
Google Scholar
Nielsen, S. F., Bojesen, S. E., Schnohr, P. & Nordestgaard, B. G. Elevated rheumatoid factor and long term risk of rheumatoid arthritis: a prospective cohort study. BMJ 345, e5244 (2012).
Google Scholar
Shapiro, S. C. Biomarkers in rheumatoid arthritis. Cureus 13, e15063 (2021).
Google Scholar
Kurowska, W., Kuca-Warnawin, E. H., Radzikowska, A. & Maslinski, W. The role of anti-citrullinated protein antibodies (ACPA) in the pathogenesis of rheumatoid arthritis. Cent. Eur. J. Immunol. 42, 390–398 (2017).
Google Scholar
Buhlmann, D. et al. FHR3 blocks C3d-Mediated coactivation of human B cells. J. Immunol. 197, 620–629 (2016).
Google Scholar
Friese, M. A. et al. Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects synovial fibroblasts during rheumatoid arthritis. Clin. Exp. Immunol. 132, 485–495 (2003).
Google Scholar
Luce Perie, S. et al. Unique target binding by the C-terminal region of FHR1 provides a new perception of aHUS pathology Front. Hematol. 3. (2024).
Dopler, A. et al. Deregulation of factor H by factor H-related protein 1 depends on sialylation of host surfaces. Front. Immunol. 12, 615748 (2021).
Google Scholar
Tak, P. P. & Bresnihan, B. The pathogenesis and prevention of joint damage in rheumatoid arthritis: advances from synovial biopsy and tissue analysis. Arthritis Rheumatol. 43, 2619–2633 (2000).
Google Scholar
Firestein, G. S. Evolving concepts of rheumatoid arthritis. Nature 423, 356–361 (2003).
Google Scholar
Fritsche, L. G. et al. An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD). Hum. Mol. Genet. 19, 4694–4704 (2010).
Google Scholar
