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Objectives To evaluate the proportions of rheumatoid arthritis (RA) sera containing anticitrullinated proteins autoantibodies (ACPA) reactive to α36-50Cit38,42 and/or β60-74Cit60,72,74, two peptides identified as bearing the immunodominant epitopes of their major target, citrullinated fibrin. To analyse the relationships of anti-α36--50Cit38,42 and anti-β60-74Cit60,72,74 autoantibodies with autoantibodies reactive to the complete citrullinated human fibrinogen molecule (AhFibA) and with anti-CCP2 antibodies. Methods 617 sera from 181 patients with established RA and 436 with non-RA rheumatic diseases were tested by ELISA for AhFibA, anti-CCP2, anti-α36- 50Cit38,42, anti-β60-74Cit60,72,74 autoantibodies, and by nephelometry for rheumatoid factor (RF). Diagnostic indexes, correlations and concordances between tests were analysed. Crossreactivity of anti-α36-50Cit38,42 and anti-β60-74Cit60,72,74 autoantibodies was assessed in competition experiments. Results At a diagnostic specificity of 95%, the diagnostic sensitivity of AhFibA (83%) was significantly higher than that of all other tests. The diagnostic sensitivity of anti-β60-74Cit60,72,74 (71%) was significantly higher than that of anti-α36-50Cit38,42 autoantibodies (51%) but similar to that of anti-CCP2 (74%). Titres of RF, anti-α36-50Cit38,42 and anti-β60-74Cit60,72,74 autoantibodies were weakly correlated with each other, whereas titres of anti-β60-74Cit60,72,74 were strongly correlated with those of AhFibA (r=0.633) and anti-CCP2 (r=0.634). Anti-α36-50Cit38,42 and anti-β60-74Cit60,72,74 mainly corresponded to two noncrossreactive subfamilies of ACPA. More than 90% of AhFibA-positive or anti-CCP2-positive sera recognised the α36-50Cit38,42 and/or the β60-74Cit60,72,74 peptide. Conclusions Autoantibodies reactive to α36-50Cit38,42 and β60-74Cit60,72,74 form two distinct, non-overlapping subfamilies of ACPA that, together, cover practically all the ACPA reactivity to citrullinated fibrinogen and to CCP2 antigens. In established RA, anti-β60-74Cit60,72,74 autoantibodies show diagnostic indexes similar to those of anti-CCP2. [ABSTRACT FROM AUTHOR]

Summary: Objective: Osteoarthritis (OA) epidemiologic data are scarce in Europe. To estimate the prevalence of symptomatic knee and hip OA in a multiregional sample in France. Design: A two-phase population-based survey was conducted in six regions in 2007–2009. On initial phone contact using random-digit dialing, subjects 40–75 years old were screened with a validated questionnaire. Subjects screened positive were invited for ascertainment: physical examination and hip and/or knee radiography (Kellgren–Lawrence grade≥2). Multiple imputation for data missing not-at-random was used to account for refusals. Results: Of 63,232 homes contacted, 27,632 were eligible, 9621 subjects screened positive, 3707 participated fully in the ascertainment phase, and 1010 had symptomatic OA: 317 hip, 756 knee. Hip OA prevalence according to age class ranged from 0.9% to 3.9% for men and 0.7–5.1% for women. Knee OA ranged from 2.1% to 10.1% for men and 1.6–14.9% for women. Both differed by geographical region. The hip and knee standardized prevalence was 1.9% and 4.7% for men and 2.5% and 6.6% for women, respectively. Conclusions: This confirmed the feasibility of using a screening questionnaire for eliciting population-based estimates of OA. In France, it increases with age and is greater among women above the age of 50. The geographical disparity of hip and knee OA parallels the distribution of obesity. Study registration ID number 906297 at http://www.clinicaltrials.gov/. [ABSTRACT FROM AUTHOR]

Background: In rheumatoid arthritis (RA), antibodies to citrullinated protein (ACPA) are believed to be heterogeneous and patient stratification by antibody profiling raised clinical interest for patient management. However, heterogeneity might be partially artificial because of the use of heterogeneous methods for ACPA detection. In recent work instead, we found that ACPA were mainly directed towards a single fibrin-derived peptide, β60-74BiotNt, but a comparative analysis with the presence of other ACPA specificities is still lacking., Objectives: To present an overview of RA patients' stratification based on the detection of the main ACPA fine specificities with the same method as compared to that of anti-β60-74BiotNt antibodies., Methods: Over 4500 measurements were performed with more than 22 standardised ELISAs, sera from 180 RA patients and 200 to 436 non-RA rheumatic disease controls., Results: Four to 81% of RA patients had ACPA towards various targets, confirming the heterogeneity of ACPA specificities. However, the subgroups of patients overlapped up to 97% with ACPA levels of correlation coefficients up to 0.8, showing redundancy of some targets. Multiplexing decreased diagnostic specificity from 95% to 64%. Instead, anti-β60-74BiotNt detection identified almost all ACPA-positive patients., Conclusions: Antibodies to citrullinated protein multiplexing shows some degree of redundancy and is not suitable for diagnostic purposes. ACPA fine specificities might be less heterogeneous than perceived by sera testing on multiple peptides. Patient stratification largely depends on detection methods and requires standardisation., Competing Interests: We declare no conflicts of interest., (© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Quantification of Abs toward a single epitope is critical to understanding immunobiological processes. In autoimmunity, the prognostic value of the serological profiles of patients draws much attention, but the detection of Abs toward a single epitope is not well controlled. Particularly, the rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide Abs (ACPA) are specific to a two-atom change on arginyl residues and are considered a heterogeneous family of Abs. As a model, we studied ACPA to decipher how peptide features used as immunosorbent impact Ab detection. We synthesized 30 peptides encompassing immunodominant epitopes of citrullinated fibrin differing by their length and biotin location and tested them using ELISA with 120 sera from RA and non-RA rheumatic disease controls, generating over 3000 experimental measurements. We showed that minor molecular changes in peptide chemical structure had dramatic consequences. Even when peptides exhibited the same epitope, measured Ab titers were extremely variable, and patients' seropositivity was discordant in up to 50% of cases. The distance between epitope and biotin was the most critical parameter for efficient Ab detection irrespective of biotin position or peptide length. Finally, we identified a 15-mer peptide bearing a single citrullinated epitope detecting almost all ACPA-positive sera, thus revealing a high degree of homogeneity in RA autoimmune response. This integrative analysis deciphers the dramatic impact of the molecular design of peptide-based technologies for epitope-specific Ab quantification. It provides a model for assay development and highlights that the studies using such technologies can give a wrong perception of biological processes and therefore that medical use of data must be cautious., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Objective: To analyze the associations between body composition, notably low lean mass, and clinical symptoms [pain, physical function, quality of life (QoL)] in patients with symptomatic hip and/or knee OA., Methods: Cross-sectional study using data from the 3-year follow-up visit of the Knee and Hip OsteoArthritis Long-term assessment (KHOALA) cohort. Skeletal muscle and fat mass were measured by dual X-ray absorptiometry (DXA). Fat mass index (FMI) was defined as total fat mass/height 2 . Appendicular lean mass was adjusted on body mass index (ALM/BMI), and low lean mass was defined according to the definition of FNIH Sarcopenia Project recommendations. Pain and function were measured by the WOMAC index and QoL by the SF-36., Results: In total, 358 patients underwent DXA (67% women, mean [SD] age 63.4 [8.4] years, mean BMI 29.5 [5.6]kg/m 2 ). The visual analog scale (0-100) pain score was 38.0 [24.7] and 25.4% had hip and 74.6% knee OA. Low lean mass and ALM/BMI were associated with impaired QoL and WOMAC scores on bivariate analysis (all p ≤ 0.001) but not on multivariate analysis after adjustment for FMI. For patients with normal BMI, mean [SD] WOMAC scores were higher (greater impairment) with low lean mass than normal body composition (WOMAC function 33.4 [23.3] and 24.0 [17.4], p = 0.02), and mean SF-36 physical component score was lower (greater impairment) 40.3 [10.2] and (44.3 [8.4], p = 0.04). Among patients with obesity, low lean mass had no additional effect., Conclusion: For patients with OA and normal BMI, QoL and function were more impaired for those with than without low lean mass. Conserving muscle mass in people with OA could have functional and antalgic benefits especially for those with normal BMI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To assess the effects of variations in hip morphology on prevalence, clinical severity and progression of hip osteoarthritis., Methods: From 2007 to 2009, we conducted a study of 242 patients aged between 40 and 75 years with symptomatic lower limb osteoarthritis, as part of a population-based osteoarthritis cohort study in France. Standard radiographs of both hips were obtained at baseline and at three years. The progression of hip osteoarthritis was evaluated according to the radiological Kellgren-Lawrence score (KL) and clinical severity from the scores on a Visual Analogic Scale (VAS) for pain recorded yearly. Five measures were used to describe hip morphology: centre edge angle, acetabular index (AI), vertical centre anterior angle, acetabular depth and neck-shaft angle., Results: Of the 484 hips studied, 205 (42%) showed osteoarthritis at baseline and 16 (11 right and 5 left) underwent joint replacement during the follow-up. AI was the morphological measure most consistently and strongly associated with radiographic osteoarthritis at baseline (odds-ratio=1.05, 95% CI: 1.01-1.08 per degree of angle change), clinical severity (correlation coefficient with VAS during 3 years=0.15, P=0.004), radiological progression (odds-ratio=1.05, 95% CI: 1.00-1.10 per degree) and joint replacement (hazard ratio=1.18, 95% CI: 1.07-1.29 per degree)., Conclusions: Acetabular obliquity and especially AI is strongly, and likely causally, associated with the existence, severity and progression of hip osteoarthritis., (Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: Our objective was to compare the use of both anteroposterior (AP) extended-knee X-ray and semi-flexed X-ray (current gold standard) versus the use of semi-flexed X-ray alone to detect femoro-tibial osteoarthritis (OA)., Methods: Individuals 40 to 75 years of age with symptomatic hip and/or knee OA (Kellgren/Lawrence [KL] score≥2) were recruited using a multiregional prevalence survey in France. Both AP and schuss X-rays were performed and read; two years later, the same examiner, blinded to the results of the first reading, performed a second reading of the schuss X-ray. We compared the KL stages of each knee and analyzed osteophyte detection and localization, joint space narrowing (JSN), and the relationship to obesity., Results: The analysis included 350 participants with OA of various stages. Comparing the two readings showed that a higher proportion of patients had KL≥2 when the two X-ray views were combined (right knee: P<0.0001; left knee: P<0.001). There were no differences when using the schuss X-ray alone versus in combination with an AP X-ray in terms of detecting JSN, osteophytes. A comparison of schuss X-ray alone versus AP X-ray alone demonstrated the superiority of the schuss view for evaluating JSN (P=0.0001 and P=0.0001) and no difference in osteophyte detection., Conclusion: Our study shows that the schuss view alone was sufficient for detecting knee osteophytes and JSN. Using one X-ray rather than two will reduce medical costs and irradiation burden. Using two views seems preferable for epidemiological studies., (Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: The relationship between acetabular dysplasia (HD) and hip osteoarthritis (OA) remains unclear, especially for mild forms of dysplasia. Our objectives were to estimate the prevalence of HD in a population-based sample with symptoms and to evaluate potential associations linking HD, hip OA, and hip pain., Methods: Individuals 40 to 75 years of age with symptoms in 1 or both hips were recruited during a multiregional prevalence survey. All study participants underwent examination and radiographs. Radiographs were evaluated using Kellgren-Lawrence staging (with stages ≥ 2 indicating hip OA) and HD measures [center-edge (CE) angle, acetabular inclination angle (HTE), acetabular depth (AD), and vertical center-anterior margin angle]., Results: We studied both hips of 842 individuals (1684 hips), among whom 203 had hip OA. Compared to left hips, right hips had significantly smaller CE angles and significantly greater AD and HTE values (p ≤ 0.001). Overall, the prevalence of HD ranged from 7.6% to 22.2% of the hips depending on the measure used. The prevalence of HD was higher in individuals with hip OA, with significant differences for abnormal HTE (19.1% vs 11.4%; p < 0.0001) and abnormal CE (11.3% vs 7.5%; p = 0.04). By logistic regression, only abnormal HTE remained associated with OA. Same-side hip pain was not statistically more common in individuals with HD after stratification on OA status (p = 0.12)., Conclusion: Our study confirms the relationship between OA and HD, particularly as defined based on the HTE angle.

Objectives: This study aimed to describe the prevalence of symptomatic knee and hip osteoarthritis (OA) and its course over time, as well as identify prognostic factors of OA course and determinants of costs and access to care in France in a patient cohort., Methods: Subjects aged 40 to 75 years, with uni- or bilateral symptomatic hip and/or knee OA (ACR criteria), Kellgren and Lawrence (KL) stage 2 or greater, were recruited from a French national prevalence survey for the multicenter KHOALA cohort study. Data collected at baseline included sociodemographic and clinical data; WOMAC, IKS and Harris scores for pain and function; MAQ score for physical activity; functional comorbidity index; GHQ28 score for psychological status; and SF-36 (generic) and OAKHQOL (specific) scores for quality of life. Blood and urine samples were collected., Results: Eight hundred and seventy-eight subjects were included, 222 with OA of the hip (mean age 61.2±8.8 years), 607 knee (mean age 62.0±8.5 years) and 49 both hip and knee (mean age 64.9±7.9 years). Mean body mass index was 26.9±4.5 for hip OA and 30.3±6.3 for knee OA. Hip and knee OA patients had 1.99 and 2.06 comorbidities, on average, respectively. Disease severity on X-rays for KL stages 2, 3 and 4 for hip OA was 69.8, 26.1 and 4.1%, respectively, and for knee OA, 44.5, 30.3, and 25.2%. As compared with population norms, age- and sex-standardized SF-36 scores were greatly decreased for both knee and hip OA in all dimensions, particularly physical and emotional dimensions., Perspectives: Patients will be followed up annually, alternately by mail and clinical visit. This cohort of representative patients with knee and hip OA will be an opportunity for future collaborative research., (Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Ideally, treatment is based on etiology, if possible on pathophysiology, and in practice on anatomical and clinical findings. A systematic search for the etiological factors of osteoarthritis (OA) shows that the various mechanisms are frequently associated. Etiological treatments are rare. We may mention acetabular tectoplasty in hip dysplasia with minimal joint space narrowing. Valgus osteotomy would also be indicated for early medial tibiofemoral OA in genu varum if we had definite proof that, if left untreated, this deformity inevitably leads to clinically severe OA. This is not the case. One of the limitations of this etiological treatment lies in the fact that we do not know which patients are at risk of developing painful OA. Instead, certain risk factors for OA are known, so that primary and secondary prevention of the disease is possible. While age, sex and genetic predisposition are not amenable to preventive action, the same does not apply to the following factors: obesity, sports, and occupational activity. Thanks to in vitro studies of cultured normal and osteoarthritic chondrocytes and to experimental models of OA in animals, the pathophysiological mechanisms of OA are beginning to be better known. The prospect thus arises of "therapeutic manipulations" of precise pharmacological targets, even if it is still too soon to speak of true pathophysiological treatment of this disease. For instance, various interventions along the IL-1 pathway can be envisaged and have all been tested in animals. In practice, treating OA means taking into consideration its various signs: pain which appears to be mechanical and more or less chronic, joint stiffness, instability, effusion, and--the consequence of these symptoms--the professional, social and personal handicap of the patient. The treatment of OA must be approached from a global perspective, associating whenever possible symptomatic treatment, disease-modifying treatment, education and rehabilitation. In other words, the treatment of OA requires an overall approach, associating pharmacological and non-pharmacological modalities.

Etiological factors in finger osteoarthritis are both local (single injury or repetitive joint use) and general. Epidemiological studies, twin studies, and studies of the ethnic influence have established that genetic factors play a role. The disease is more common in postmenopausal women, suggesting an influence of hormonal factors. Findings from studies of associations between finger osteoarthritis and osteoarthritis at other sites (spine, hips, knees), hyperostosis, and obesity, as well as the fact that the disease is less common in patients with osteoporosis and absent in hemiplegia, suggest that the concept of "osteoarthritic disease" is relevant.