Anti carbamylated protein antibodies as a diagnostic marker in patients with rheumatoid arthritis and its association with disease activity

Background Despite the diagnostic contribution of anti-citrullinated protein( anti-CCP) antibody and rheumatoid factor (RF), approximately one-third of patients with rheumatoid arthritis (RA) remain seronegative .Anti-carbamylated protein (Anti-Carp) antibodies have been attracting increasing attention as a new diagnostic marker of RA. Objective evaluate levels of anti-carp antibodies in RA patients in order to detect its role as a diagnostic marker and its possible association with disease activity and severity. Methods This study included thirty adult patients with clinical evidence of rheumatoid arthritis and thirty healthy matched age and sex as controls. All underwent history taking, clinical examination, assessment of disease activity with modified Disease Activity28 (DAS28), Laboratory investigations including Complete blood count (CBC), erythrocytes sedimentation rate (ESR), C-Reactive Protein (CRP), Liver function tests, Kidney function tests, Serum uric acid, RF, anti CCP Ab, anti-Carp Ab and radiographic Assessment with Larsen score. Results Plasma levels of anti-Carp Ab were significantly higher in patients than control group (p > 0,001) with sensitivity of 73.33% and specificity of 100%.it showed significant positive correlation with CRP (r = 0.37 )(p < 0.05) as a marker of activity of RA and also there was significant positive correlation with RF and ACPA (r = 0.45)(r = 0.48) (p < 0.05) respectively as a diagnostic marker for RA. Plasma levels of anti-Carp Ab were higher in patients with more joints damage and erosions as assessed by Larsen radiological score as there was a highly significant correlation between Larsen score and serum Anti-Carp(r = 0.61)(p < 0.001).. Conclusion serum Anti–Carp antibody level was higher in RA patients which serve as a diagnostic marker for RA, also its significant correlation with CRP and Larsen score may serve as a marker for disease progression and severity.

POS0549 FUNCTIONAL IMPACT OF FOREFOOT INVOLVEMENT IN RHEUMATOID ARTHRITIS

Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly affects small joints of the hands and feet. Foot deformities may affect the patient’s gait, thus compromising their daily activities and autonomy.Objectives:The aim of this study was to analyze its functional impact.Methods:We conducted a cross-sectional study including patients diagnosed with RA according to the ACR/EULAR 2010 criteria. Demographic variables, Foot Function Index (FFI), and Health Assessment Questionnaire (HAQ) scores were analyzed. We collected data on the following clinical variables: The pain Visual Analog Scale (VAS), forefoot deformities, erythrocyte sedimentation rate (ESR), and Disease Activity Score 28 (DAS28). All patients had feet X-rays and the Larsen score was calculated. A blinded radiologist experienced in musculoskeletal imaging using a Philips HD11 device with a high-frequency linear transducer performed ultrasonography (US) of MTP joints. Synovitis was defined as an abnormal hypoechoic synovial tissue within the capsule that is not displaceable and poorly compressible and that may exhibit Doppler signals. The composite synovitis score (power doppler / grayscale ultrasound (PDUS)) was measured for each joint. The US score of each patient was defined by the sum of the composite scores of the joints studied (0-30). A p-value <0.05 was considered significant.Results:We included 31 patients (25 men and six women) with a mean age of 54.8±10.8 years old [32-70]. The mean disease duration was 8.5±7.2 years [1-37]. The mean ESR and DAS28 ESR were 33±26 mm [5-102] and 3.8±1.5 [0.6-7], respectively. Twenty-nine percent of patients had a high disease activity.Metatarsalgia was reported by 54.8% of patients with a mean VAS of 4.5±3.7 [0-9]. Forefoot deformities were noted in 42% of patients: round forefoot in 13% of cases, triangular forefoot in 29% of cases, hallux valgus in 29% of cases, Quintus varus in 29% of cases, and claw toes in 13% of cases. Corns and calluses were noted in 42% and 29% of cases respectively.X-rays showed abnormalities in 75% of patients. The mean Larsen score was 9.8±6.2 [0-28].US showed synovitis in 46.3% of MTP1, in 53.7% of MTP2, in 48.3% of MTP3, in 42.6% of MTP4, and in 37% of MTP5 joints. Doppler signal was detected in 5.6% of MTP1 and MTP2, and in 3.7% of MTP3, MTP4, and MTP5 joints. The mean US score was 5.3±4.3 [0-15].The mean FFI was 66.5%. Mean rates of pain, difficulty, and disability were 89.5%, 40%, and 70% respectively. The mean HAQ score was 0.5±0.5 [0-2]. Severe disability was noted in 20% of patients.A significant positive correlation was noted between FFI and, Larsen score (r=0.214, p=0.014) and US score (r=0.420, p=0.021). A significant positive correlation was also noted between HAQ score and, foot pain VAS (r=0.555, p=0.009).Conclusion:Foot involvement is frequently seen in RA. This condition may affect patients’ autonomy. Early diagnosis and appropriate treatment are necessary in order to preserve the quality of life.Disclosure of Interests:None declared

Do anti-carbamylated protein antibodies in rheumatoid arthritis reflect local and systemic osteoporosis? A study of osteoprotegrin and receptor activator for nuclear factor kappa B ligand and radiological assessment

Background One of the most important and dangerous complications of rheumatoid arthritis (RA) is bone loss, which manifested by erosions and juxta-articular or systemic bone loss. Anti-carbamylated protein (anti-CarP) antibodies which are also called anti-homocitrulline antibodies have recently been found in RA. Increase anti-CarP antibody titres may lead to severe disease and increase the progression of bone loss. Osteoprotegrin and receptor activator for nuclear factor kappa B and its ligand (RANKL) are the main players in the pathogenesis of osteoporosis. Thus, we aimed to investigate and detect the presence and prevalence of anti-CarP in rheumatoid arthritis and their association with disease severity and osteoporosis, as well as with OPG/RANKL in 80 Egyptian RA patients to highlight this relationship which could be useful in managing RA patients with osteoporosis. Results Serum anti-CarP levels were significantly increased in the RA group compared with the control group (P< 0.001). We found a negative association between anti-CarP and anti-CCP and disease activity (r=−0.878, −0.534, respectively, P<0.001). We also found a positive correlation between anti-CarP and the Larsen score, DEXA score, RF, HAQ, and RANKL (r=0.646, 0.287, 0.243, 0.892, 0.671, 0.869 [respectively], P<0.001) and there was negative correlation between anti-CarP and OPG (r=−0.553, P<0.001). Conclusion Anti-CarP antibodies are associated with disease severity and disability in RA patients. They could play an important and significant role in the pathogenesis of osteoporosis in these patients.

Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis: a prospective longitudinal inception cohort study

IntroductionAnticitrullinated peptide antibody (ACPA) responses for 22 citrullinated peptides in patients with early rheumatoid arthritis (RA) were analysed and related to radiological and clinical outcome during the first 2 years in a prospective inception cohort.MethodsThe ACPA reactivities were assessed in 1022 patients with early RA (symptoms <12 months) using the custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden) in a prospective longitudinal study of observational assessments of Disease Activity Score (DAS28 and its components) and radiology during the first 24 months, accounting for the treatment.ResultsFrequency of ACPA reactivities varied between 13.3% and 63.1%. Of the anticyclic citrullinated peptide-2 (anti-CCP2) antibody-negative patients, ACPA reactivities were positive in 32.6%. Smoking, human leucocyte antigen-shared epitope (HLA-SE), anti-CCP2/rheumatoid factor, protein tyrosine phosphatase non-receptor type 22 (1858C/T) and DAS28 were significantly associated with number of ACPA reactivities. The ACPA reactivities modified differently the development of DAS28 over 24 months (identified using trajectories). Anti-Filaggrin307-324, anti-hnRNP (Peptide)-Z1 and anti-F4-CIT-R antibodies anticipated lower DAS28 values (p<0.01–0.05), while positivity for anti-Fibrinogen(Fib)β62-78(74), and anti-Fibα563-583 predicted higher DAS28 (p<0.01 both). Interaction between anti-Fibß36-52, anti-Pept-5 and anti-Bla-26 antibodies, respectively, and DAS28 during 24 months decreased significantly the DAS28 values (p<0.01–0.05). Corticosteroids and biologicals were related to DAS28-area under the curve and Larsen score 24 months. Anti-vimentin2-17 antibodies remained significantly associated with Larsen score at baseline and 24 months, respectively, and radiological progression, besides biologicals at 24 months adjusted for sex and age.ConclusionsSeveral ACPA reactivities modified significantly the DAS28 development during the first 24 months and were significantly associated with Larsen score at baseline, 24 months and radiological progression.

Six-month prospective trial in early and long-standing rheumatoid arthritis: evaluating disease activity in the wrist through sequential synovial histopathological analysis, RAMRIS magnetic resonance score and EULAR-OMERACT ultrasound score

IntroductionStandardised scoring systems for rheumatoid arthritis (RA) joint disease activity include Larsen score for radiographs, rheumatoid arthritis magnetic resonance imaging score (RAMRIS) for MRI and using the European League Against Rheumatisms-Outcome Measures in Rheumatology (EULAR-OMERACT) score for ultrasound (US) images. The aim of this prospective study was to investigate the relationship between histological synovitis and radiological synovitis, assessed by conventional X-ray, US and MRI of the wrist radiocarpal joint.Methods20 patients with treatment naive early RA (ERA) and 20 with long-standing RA (LRA) were enrolled in a 6-month prospective study. Patients with RA underwent US-guided synovial biopsy, X-ray and US of the wrist at enrolment and 6 months. MRI at baseline and also at 6 months for the ERA group, and scored with the RAMRIS system. X-ray was scored by Larsen score and US by the EULAR-OMERACT system. Synovial biopsy inflammation was determined by the Krenn score.ResultsIn the ERA group at baseline, Krenn score was correlated strongly with both US combined score (r = 0.77 p < 0.001) and MRI synovitis score (r = 0.85 p < 0.001), while uncorrelated at 6 months. In the LRA group at baseline, these scores correlated strongly (r = 0.83, p < 0.001) to moderately (r = 0.61, p = 0.002), and persisted at 6 months for US score (r = 0.81 p < 0.001). For all patients with RA, change in Krenn score between baseline and 6 months was correlated with both change in US combined score (r = 0.65, p < 0.001) and change in MRI synovitis score (r = 0.50, p = 0.03).ConclusionThe MRI RAMRIS synovitis score and EULAR-OMERACT US scoring system are sensitive measures of histological synovitis in LRA and ERA. After 6 months, this correlation persists in the established RA group, but not in the ERA group. Overall, decreases in MRI/US synovitis are associated with reductions in histological synovitis. The study validates the use of MRI RAMRIS and EULAR-OMERACT US scores as surrogate markers of histological synovitis in established RA and early untreated RA.

Association of the A Allele of the TNF-Alpha-308 G/A Gene Polymorphism with Radiographic Progression in Rheumatoid Arthritis

Summary To examine whether the presence of the rare A allele of the TNF-Alpha-308 G/A gene polymorphism is associated with erosive arthritis and rapid radiological progression of the disease. The examined group included 131 patients with early RA. Using the PCR-RFLP method, the TNF-Alpha-308 G/A gene polymorphism was determined for all patients. In relation to the presence of the A allele of the examined polymorphism, the patients were divided into two subgroups: subgroup A (G/A and A/A genotypes) and subgroup G (G/G genotype). Based on the presence of the destructive changes in joints found in the initial radiographs, the findings were classified as erosive and non-erosive RA. Radiological progression was assessed on the basis of the annual change in the Larsen score – LS (0-200). Group A comprised 62 (47.33%) patients, while group G comprised 69 (52.67%) patients. The presence of cysts and erosions in subgroups A and G was compared before the start of the methotrexate therapy. It was determined that erosions (erosive RA) were statistically significantly more frequent in group A (83.87% of patients) in comparison with group G (44.93% of patients), p < 0,001. Group A patients had a higher value of the Larsen score in relation to the group G both before and after methotrexate was administered for a year (before therapy, LS in group A: 48.58 ± 20.54; in group G 20.73 ± 12.31; p < 0.01; after MTX therapy, LS in group A: 58.32 ± 22.25; in group G 25.35 ± 14.57; p < 0.001). The average value of the annual LS change in group A was statistically significantly greater than the change in group G patients (9.98 ± 4.95 to 5.23 ± 2.72) (p < 0.05). The presence of the A allele of the TNF-Alpha-308 G/A gene polymorphism is associated with the occurrence of early erosive joint changes and more rapid radiological progression of the disease.

Is It the Age at Disease Onset or the Disease Radiological Severity That Affects Cervical Spine Involvement in Patients With Rheumatoid Arthritis?

Background: Cervical spine involvement in patients with rheumatoid arthritis (RA) can cause pain and disability, with a variety of neurologic signs and symptoms. Objectives: To investigate the relationship between structural cervical spine involvement in patients with RA with the age at disease onset and the degree of radiologic severity of RA measured by Larsen scoring. Patients and methods: This cross-sectional study included 50 adult patients with RA. Patients who complained or not complained from symptoms of cervical spine involvement in RA were included; we did X-ray of the cervical spine, hands, and feet; Larsen scoring method; disease activity score (DAS28); and Neck Disability Index. Results: The results revealed that patients with cervical involvement tend to be younger at their disease onset than those with no cervical involvement, as detected by cervical X-ray. The relation was significant P < .05 regarding all cervical involvements except for basilar invagination. Disease radiological severity (measured by Larsen score) significantly increases the risk for subaxial subluxation, P = .040. All other cervical complications of RA tend to have nonsignificant relation with disease severity. Using univariate binary regression analysis for risk factors for cervical involvement showed that the only probable risk factor for cervical involvement (detected by X-ray) in patients with RA is age at disease onset. Conclusions: The early age at disease onset tends to affect cervical spine involvement in patients with RA more than the disease radiological severity.

Radiocarpal and Midcarpal Instability in Rheumatoid Patients: A Systematic Review

Background: This study was aimed at identifying the criteria for the diagnosis of Radiocarpal instability in rheumatoid arthritis RA). Methods: The main databases were searched to identify studies describing the pathophysiology of Radiocarpal instability in patients with RA. We focussed on the epidemiology, radiographic parameters, criteria for instability and on treatment options. Results. In the search 108 articles were found, of these 12 studies were included for this review. Instability occurs in at an average of 35.2% of the rheumatoid wrists. The instability was found between 8 and 13 years after onset of rheumatoid arthritis. A strong correlation was found between instability, duration of RA and Larsen score. Several radiographic methods were described to evaluate Radiocarpal instability in RA. Several treatment options for instability in patients with RA are described. All with their own indications and limitations. Conclusion: OOn a standard AP radiograph deformity can be measured using the carpal height and the ulnar translation index of Chamay. This gives an indication for instability. For describing the deterioration of the joints the Larsen score is most used. If there are more radiographs in time the Simmen classification can be used. For real assessment of instability dynamic radiographs are needed. Level of Evidence: Level IV.

Is Lipoprotein-Associated Phospholipase A2 a Link between Inflammation and Subclinical Atherosclerosis in Rheumatoid Arthritis?

Objective. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker of vascular inflammation, is associated with cardiovascular disease. This prospective study of an inception cohort aimed to investigate whether the level of Lp-PLA2 is associated with subclinical atherosclerosis in patients with rheumatoid arthritis (RA).Methods. Patients from northern Sweden diagnosed with early RA were consecutively recruited into an ongoing prospective study. From these, all patients ≤60 years (n=71) were included for measurements of subclinical atherosclerosis at inclusion (T0) and five years later (T5). Forty age- and sex-matched controls were included. The patients were clinically assessed, SCORE, Reynolds Risk Score, and Larsen score were calculated, and blood samples were drawn from all individuals at T0 and T5.Results. There was no significant difference in the level of Lp-PLA2 between patients with RA and controls (p>0.05). In simple linear regression models among patients with RA, Lp-PLA2 at T0 was significantly associated with intima media thickness (IMT) at T0 and T5, flow mediated dilation (FMD) at T0 and T5, ever smoking, male sex, HDL-cholesterol (inversely), non-HDL-cholesterol, SCORE, Reynolds Risk Score, and Larsen score (p<0.05).Conclusion. In this cohort of patients with early RA, the concentration of Lp-PLA2 was associated with both subclinical atherosclerosis and disease severity.

Discrepancy Between Clinical and Radiological Responses to Tocilizumab Treatment in Patients with Systemic-onset Juvenile Idiopathic Arthritis

Objective.Tocilizumab (TCZ), an antiinterleukin-6 receptor monoclonal antibody, is clinically beneficial in patients with systemic-onset juvenile idiopathic arthritis (sJIA). We investigated the clinical and radiological outcomes of TCZ therapy in patients with sJIA.Methods.We retrospectively evaluated 2 clinical trials (NCT00144599 and NCT00144612) involving 40 patients with sJIA who received intravenous TCZ (8 mg/kg) every 2 weeks. Clinical data and radiographs of the hands and large joints were assessed before and during TCZ treatment. The Poznanski score, modified Larsen scores of the hands and large joints, and Childhood Arthritis Radiographic Score of the Hip (CARSH) were recorded.Results.After a mean duration of 4.5 years of TCZ treatment, clinical data had improved significantly, the mean Poznanski score improved from −1.5 to −1.1, the mean Larsen score of the hands deteriorated from 7.0 to 10.0, the mean Larsen score for the large joints deteriorated from 5.9 to 6.8, and the CARSH worsened from 3.9 to 6.2. The Larsen score for the large joints improved in 11 cases (28%), remained unchanged in 8 cases (20%), and worsened in 21 cases (52%). Matrix metalloproteinase 3 (MMP-3) levels remained significantly higher (278 mg/dl) in patients with worsened Larsen scores than in patients with improved or unchanged scores (65 mg/dl). Logistic regression analysis showed that older age at disease onset was a significant risk factor for radiographic progression.Conclusion.The modified Larsen score of the large joints deteriorated in half the patients who had high MMP-3 levels during TCZ treatment and who were significantly older at disease onset.