Anti-carbamylated protein (anti-CarP) antibodies precede the onset of rheumatoid arthritis

Shi, Jing; Stadt, Lotte A van de; Levarht, E. W. Nivine; Huizinga, Tom W J; Hamann, Dörte; Schaardenburg, Dirkjan van; Toes, René E. M.; Trouw, Leendert A.

doi:10.1136/annrheumdis-2013-204154

Cited by 189 publications

(159 citation statements)

References 22 publications

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“…Moreover, several CF serum samples reacted with both fibrinogen and carbamylated fibrinogen but not with nBPI. Reactivity of CF sera to carbamylated fibrinogen parallels previously observed autoreactivity in RA patients (41). Thus, autoantibodies in CF sera react with specificity with the denatured forms of nBPI, fibrinogen, and carbamylated fibrinogen.…”

Section: Resultssupporting

confidence: 66%

The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

Skopelja¹,

Hamilton²,

Jones³

et al. 2016

JCI Insight

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Section: Resultssupporting

confidence: 66%

The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

Skopelja¹,

Hamilton²,

Jones³

et al. 2016

JCI Insight

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“…The sera autoantibodies are polyclonal and reactive to Ig (RF) [6], ACPAs [13] or carbamylated fetal calf serum (anticarb antibodies) [14]. There is a strong environmental component, rather than MHC genetics, driving the production of the RA autoantibodies, as shown in twin studies [15], indicating a role for the innate immune system.…”

Section: Stage 1 -Autoimmune Priming In Healthy Individualsmentioning

confidence: 99%

Autoimmune priming, tissue attack and chronic inflammation — The three stages of rheumatoid arthritis

2014

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Extensive genome-wide association studies have recently shed some light on the causes of chronic autoimmune diseases and have confirmed a central role of the adaptive immune system. Moreover, better diagnostics using disease-associated autoantibodies have been developed, and treatment has improved through the development of biologicals with precise molecular targets. Here, we use rheumatoid arthritis (RA) as a prototype for chronic autoimmune disease to propose that the pathogenesis of autoimmune diseases could be divided into three discrete stages. First, yet unknown environmental challenges seem to activate innate immunity thereby providing an adjuvant signal for the induction of adaptive immune responses that lead to the production of autoantibodies and determine the subsequent disease development. Second, a joint-specific inflammatory reaction occurs. This inflammatory reaction might be clinically diagnosed as the earliest signs of the disease. Third, inflammation is converted to a chronic process leading to tissue destruction and remodeling. In this review, we discuss the stages involved in RA pathogenesis and the experimental approaches, mainly involving animal models that can be used to investigate each disease stage. Although we focus on RA, it is possible that a similar stepwise development of disease also occurs in other chronic autoimmune settings such as multiple sclerosis (MS), type 1 diabetes, and systemic lupus erythematosus.Keywords: Animal models r Autoimmunity r Rheumatology Revisiting past efforts of RA researchEven though much detail has been recently revealed on the genetics and epidemiology of autoimmune diseases, several concepts on autoimmunity have been around for a long time. Early rheumatology studies were already deeply engaged in analyzing rheumatoid factors (RFs), that is, autoantibodies to Ig, and the Correspondence: Dr. Rikard Holmdahl e-mail: Rikard.Holmdahl@ki.se strong genetic association of RA with the HLA-DR alloantigens. However, many of the underlying causes of RA and the different stages in the disease process are still unclear even with the most recent information and therefore many of the old conceptual questions remain.The main result of recent genome-wide association studies (GWAS) is the confirmation of the strong association between "classical" (RF-positive) RA and the "shared epitope" MHC class II alleles [1][2][3]. The shared epitope is a specific peptide-binding pocket, originally defined as a structure in the polymorphic DRB1 chain shared by many alleles with basic amino acids at positionwww.eji-journal.eu 1594 Rikard Holmdahl et al. Eur. J. Immunol. 2014. 44: 1593-1599 70 and 74 [2], to which one now also may add positions 11 and 13 that are also strongly associated with RA [3]. In addition, the identity of around hundred genetic loci, with minor contribution to RA susceptibility, strengthen the dogma that RA is caused by aberrant autoreactive T cells [4,5]. Even though the influence of MHC and CD4 + T cells are more validated than ever, we still search for th...

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“…These antibodies are rarely found in patients with other connective tissue diseases (CTDs) unless SSc features are also present, and thus, they are important diagnostic markers. The antibodies are nearly always present when first tested, and their presence likely precedes clinical findings by months or years, as has been confirmed in RA and SLE [7,8]. SSc antibodies typically remain detectable throughout the course of disease, independent of treatment.…”

Section: Ssc-associated Anasmentioning

confidence: 92%