Measuring ACPA in the general population or primary care: is it useful?

Finckh, Axel; Courvoisier, Delphine S.; Lamacchia, Céline; inflammatoires, Recherche clinique en rhumatismes

doi:10.1136/rmdopen-2019-001085

Cited by 15 publications

(8 citation statements)

References 85 publications

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“…The overall cohort tested over 9000 potential participants since 2008, while about >750 were included being ACPA+in line with reported prevalence of ACPA-positivity. 45 The populations and models developed for ACPA+arthralgia 22 46 are therefore not directly transferable to cohort of patients with CSA (as defined by EULAR taskforce 42 47 48 ), or in first degree relatives of patients with IA, 49–51 which are the other main characteristics used for selecting at risk individuals. In addition, progression rate in these different groups are different and if 32% for IA in our cohort, progression to RA was only observed following from the development of IA in less than 25% of cases.…”

Section: Discussionmentioning

confidence: 99%

“…As criteria are needed to define an at-risk population and to balance the specificity of the recruitment with the number of cases needed to develop models. The overall cohort tested over 9000 potential participants since 2008, while about >750 were included being ACPA+in line with reported prevalence of ACPA-positivity 45. The populations and models developed for ACPA+arthralgia22 46 are therefore not directly transferable to cohort of patients with CSA (as defined by EULAR taskforce42 47 48), or in first degree relatives of patients with IA,49–51 which are the other main characteristics used for selecting at risk individuals.…”

Section: Discussionmentioning

confidence: 99%

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Added value of multiple autoantibody testing for predicting progression to inflammatory arthritis in at-risk individuals

et al. 2022

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BackgroundPredicting progression to clinical arthritis in individuals at-risk of developing rheumatoid arthritis is a prerequisite to developing stratification groups for prevention strategies. Selecting accurate predictive criteria is the critical step to define the population at-risk. While positivity for anti-citrullinated protein antibodies (ACPA) remains the main recruitment biomarker, positivity for other autoantibodies (AutoAbs) identified before the onset of symptoms, may provide additional predictive accuracy for stratification.ObjectiveTo perform a multiple AutoAbs analysis for both the prediction and the time of progression to inflammatory arthritis (IA).Methods392 individuals were recruited based on a new musculoskeletal complaint and positivity for ACPA or rheumatoid factor (RF). ELISAs were performed for ACPA, RF, anti-nuclear Ab, anti-carbamylated protein (anti-CarP) and anti-collagen AutoAbs. Logistic and COX regression were used for analysis.ResultsProgression to IA was observed in 125/392 (32%) of cases, of which 78 progressed within 12 months. The AutoAbs ACPA, RF, anti-CarP were individually associated with progression (p<0.0001) and improved prediction when combined with demographic/clinical data (Accuracy >77%; area under the curve (AUC) >0.789), compared with prediction using only demographic/clinical data (72.9%, AUC=0.760). Multiple AutoAbs testing provided added value, with +6.4% accuracy for number of positive AutoAbs (AUC=0.852); +5.4% accuracy for AutoAbs levels (ACPA/anti-CarP, AUC=0.832); and +6.2% accuracy for risk-groups based on high/low levels (ACPA/RF/anti-CarP, AUC=0.837). Time to imminent progression was best predicted using ACPA/anti-CarP levels (AUC=0.779), while the number of positive AutoAbs was/status/risk were as good (AUC=0.778).ConclusionWe confirm added value of multiple AutoAbs testing for identifying progressors to clinical disease, allowing more specific stratification for intervention studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Added value of multiple autoantibody testing for predicting progression to inflammatory arthritis in at-risk individuals

et al. 2022

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“…The positive predictive value (PPV) of ACPA tests, which demonstrates the likelihood of an individual with a positive test to have or develop a condition, varies in different studied populations – from 9% in the general population to 55% when both environmental and genetic risk factors are present, 52% in clinically suspect arthralgia (CSA) and >80% in undifferentiated arthritis patients [ 129 ]. Multivariable analysis in one study showed ACPA-positivity to be an independent risk factor for RA development in individuals with CSA (hazard ratio (HR) = 5.1; 2.0–13.2) and to have a 50–67% PPV (RF-negative/RF-positive) for RA development within 2 years [ 125 ] .…”

Section: Clinical Relevance Of Autoantibodies In Ramentioning

confidence: 99%

Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings

Sokolova

Schett

Steffen

2021

Clinic Rev Allerg Immunol

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Autoantibodies represent a hallmark of rheumatoid arthritis (RA), with the rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA) being the most acknowledged ones. RA patients who are positive for RF and/or ACPA (“seropositive”) in general display a different etiology and disease course compared to so-called “seronegative” patients. Still, the seronegative patient population is very heterogeneous and not well characterized. Due to the identification of new autoantibodies and advancements in the diagnosis of rheumatic diseases in the last years, the group of seronegative patients is constantly shrinking. Aside from antibodies towards various post-translational modifications, recent studies describe autoantibodies targeting some native proteins, further broadening the spectrum of recognized antigens. Next to the detection of new autoantibody groups, much research has been done to answer the question if and how autoantibodies contribute to the pathogenesis of RA. Since autoantibodies can be detected years prior to RA onset, it is a matter of debate whether their presence alone is sufficient to trigger the disease. Nevertheless, there is gathering evidence of direct autoantibody effector functions, such as stimulation of osteoclastogenesis and synovial fibroblast migration in in vitro experiments. In addition, autoantibody positive patients display a worse clinical course and stronger radiographic progression. In this review, we discuss current findings regarding different autoantibody types, the underlying disease-driving mechanisms, the role of Fab and Fc glycosylation and clinical implications.

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“…The detection of circulating antibody titers against citrullinated (cyclic) peptides (CCP), e.g. anti-citrullinated peptide antibodies (ACPA) is used today for differential diagnosis, therapeutic follow-up and prognosis of patients with various forms of arthritis ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

Proteoform Analysis of Matrix Metalloproteinase-9/Gelatinase B and Discovery of Its Citrullination in Rheumatoid Arthritis Synovial Fluids

Grillet

Ugarte-Berzal

et al. 2021

Front. Immunol.

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ObjectivesTo explore posttranslational modifications (PTMs), including proteolytic activation, multimerization, complex formation and citrullination of gelatinases, in particular of gelatinase B/MMP-9, and to detect in gelatin-Sepharose affinity-purified synovial fluids, the presence of specific MMP proteoforms in relation to arthritis.MethodsLatent, activated, complexed and truncated gelatinase-A/MMP-2 and gelatinase B/MMP-9 proteoforms were detected with the use of zymography analysis to compare specific levels, with substrate conversion assays, to test net proteolytic activities and by Western blot analysis to decipher truncation variants. Citrullination was detected with enhanced sensitivity, by the use of a new monoclonal antibody against modified citrullines.ResultsAll MMP-9 and MMP-2 proteoforms were identified in archival synovial fluids with the use of zymography analysis and the levels of MMP-9 versus MMP-2 were studied in various arthritic diseases, including rheumatoid arthritis (RA). Secondly, we resolved misinterpretations of MMP-9 levels versus proteolytic activities. Thirdly, a citrullinated, truncated proteoform of MMP-9 was discovered in archival RA synovial fluid samples and its presence was corroborated as citrullinated hemopexin-less MMP-9 in a small prospective RA sample cohort.ConclusionSynovial fluids from rheumatoid arthritis contain high levels of MMP-9, including its truncated and citrullinated proteoform. The combination of MMP-9 as analyte and its PTM by citrullination could be of clinical interest, especially in the field of arthritic diseases.

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Measuring ACPA in the general population or primary care: is it useful?

Cited by 15 publications

References 85 publications

Added value of multiple autoantibody testing for predicting progression to inflammatory arthritis in at-risk individuals

Added value of multiple autoantibody testing for predicting progression to inflammatory arthritis in at-risk individuals

Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings

Proteoform Analysis of Matrix Metalloproteinase-9/Gelatinase B and Discovery of Its Citrullination in Rheumatoid Arthritis Synovial Fluids

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