Antibodies to Mutated Citrullinated Vimentin in Rheumatoid Arthritis: Diagnostic Value, Association with Radiological Damage and Axial Skeleton Affection

Abstract Background: Early definitive diagnosis and effective treatment are mandatory in rheumatoid arthritis (RA) as it can halt the disease progression and subsequent joints destruction. Objective: To investigate the diagnostic and prognostic value of anti-mutated citrullinated vimentin (anti-MCV) and its correlation with disease activity, peripheral and axial skeleton affection in RA patients. Patients and methods: A total of 123 patients with different rheumatic diseases were enrolled in a prospective-two year study at Ain Shams University hospital: 64 patients with RA and 59 patients with other rheumatic diseases as controls. RA patients were fulfilling the traditional and the new ACR/EULAR diagnostic criteria for RA. They have been followed up for two years. At baseline, all RA patients were subjected to: Clinical assessment of disease activity by taking full histories, general and local examination, measurement of 28 joint count of tender and swollen joints with calculation of disease activity score (DAS-28) for each patient. Complete blood count, erythrocytes sedimentation rate, C-reactive protein and rheumatoid factor titers were performed. Anti-MCV IgG immunoglobulins’ assay was performed at the study endpoint by ELISA. RA patients were then classified into; anti-MCV positive and anti-MCV negative groups for statistical comparison. Plain X-ray was performed on the peripheral joints and scored by the Simple Erosion Narrowing score (SEN-score). Magnetic Resonance Imaging (MRI) scans were carried out to 22 RA patients on cervical and lumbosacral regions. Results: Anti-MCV antibodies were found to be of high sensitivity (79.6%) and specificity (96.6%) in diagnosing RA. The area under the curve was 0.893 at 95% confidence interval (CI), confers an odds ratio of 23.5. Anti-MCV positive RA patients had significantly higher DAS-28 and SEN-scores than anti-MCV negative patients; who were found to have more benign disease with lower incidence of erosions (P , 0.05). MRI scans revealed that; 17/22 (77%) had cervical joints involvement while, 8 (36%) had lumbo-sacral joint lesions (P , 0.05), both were correlated significantly with aggressive peripheral joint disease. Conclusion: Anti-MCV antibodies are promising diagnostic and prognostic marker in RA, with high sensitivity and specificity. They may identify a subset of RA patients with aggressive early erosive disease. The axial skeleton—especially the cervical spine—could be affected in RA and this was correlated with aggressive peripheral joints’ disease. MRI scanning is a sensitive method for detecting axial skeleton involvement in RA, in attempt for better disease control and outcomes

Bone Mineral Density Changes in Patients with Recent-Onset Rheumatoid Arthritis

Background Osteoporosis and related fragility fractures are one of the most common complications seen in patients with rheumatoid arthritis (RA) and dramatically affect quality of life. Objective To evaluate changes in bone mineral density in patients with recent onset rheumatoid arthritis (< 1 year) and its correlation if any with a modified DAS-28 score and simple erosion narrowing score (SENS). Methods This study included 30 patients with recent-onset rheumatoid arthritis fulfilling the new American College of Rheumatology/European League Against Rheumatism diagnostic criteria for rheumatoid arthritis and 20 healthy volunteers as controls. All were subjected to a complete blood count, erythrocyte sedimentation rate, C-reactive protein, liver function tests, renal function tests, rheumatoid factor, and plain x-rays of the hands and feet. Dual-energy x-ray absorptiometry DEXA was used to measure bone mineral density (BMD) of the left proximal femur, lumbar spine (L1–L4), and lower distal radius at the time of recruitment. Results In the RA patients, 13.3% had osteoporosis, 50% had osteopenia, and 36.7% had normal BMD. The most common site of osteoporosis was the lumbar spine (four patients, 13.3%) followed by the femur (two patients, 6.6%), and forearm (only one patient, 3.3%). There was a significantly higher percentage of osteoporosis among RA males than females and the difference was statistically significant ( P = 0.009). Osteoporosis was more common in patients treated with corticosteroids and disease modifying antirheumatic drugs (DMARDs) than in patients treated with only nonsteroidal anti-inflammatory drugs ( P = 0.004). Higher disease activity (DAS-28) was found in RA patients with osteoporosis compared to RA patients with normal BMD or osteopenia, but the difference was not statistically significant. Osteoporotic RA patients were found to have a higher SENS score for radiological damage than nonosteoporotic ones. Conclusion BMD changes do occur in patients with early RA, and are not necessarily correlated with disease activity (DAS-28). However, a significant negative correlation was found between BMD and the score of radiological damage (SENS). Dual energy x-ray absorptiometry is an important investigation to assess BMD in early RA patients

Anti-Annexin V Antibodies: Association with Vascular Involvement and Disease Outcome in Patients with Systemic Sclerosis

Background: Systemic Sclerosis (SSc) is characterized by skin thickening, fibrosis and vascular obliteration. The onset and course are heterogeneous. Prominent features include autoimmunity, inflammation and vascular damage. Aim of study: To measure the level of serum Anti-Annexin V antibodies in SSc patients and to study its significance in relation to vascular damage in these patients. Patients and methods: Twenty patients with SSc (12 with diffuse SSc and 8 with the limited form) and 10 healthy age and sex matched volunteers as controls were all subjected to routine laboratory testing and immunological profiling including antinuclear, anti-Scl-70, anticentomere, anticardiolipin antibodies and anti-annexin V antibodies titres. Vascular damage was assessed by clinical examination and assessment of the disease activity score, nailfold capillaroscopy and colour flow Doppler of the renal arteries; Doppler echocardiography was used for assessing pulmonary hypertension. Results: Anti-annexin V antibodies were detected in 75% of patients. Comparisons between anti-annexin V in diffuse and limited subgroups showed no significance; however a statistically significant positive correlation was found between Anti-annexin V titre and the degree of vascular damage in SSc patients. Anti-annexin V increased significantly in patients with severe vascular damage in comparison with those less affected (15.3 ± 6.6 vs. 11.25 ± 3.6, P , 0.05). A significant positive correlation was found between Anti-annexin V titre and both the ACL titre (r = 0.79, P , 0.001) and the resistive index of the main renal artery (r = 0.42, P , 0.05). Conclusion: Anti-annexin V antibodies were significantly present in sera of patients with SSc. Patients with more severe forms of vascular damage had higher titres of these antibodies. Anti-annexin V antibodies are a sensitive predictor of vascular damage in SSc and could serve as a useful parameter in discriminating patients with a higher risk of vascular affection from those without

Subclinical neuropsychiatric dysfunctions in female patients with systemic lupus erythematosus

Objective To examine for presence of subclinical neuropsychiatric lupus and cerebral atherosclerosis and their correlation with MRI/magnetic resonance angiography (MRA) findings and disease activity and to find if these radiological changes compared with laboratory parameters could be predictive of the early NP affection aiming for early management of these dysfunctions. Patients and methods Thirty adult female patients with systemic lupus erythematosus (SLE) were enrolled, with assessment of SLE disease activity using Systemic Lupus Erythematosus Disease Activity Index; psychometric evaluations using the Modified Mini-Mental State Examination to assess for cognitive dysfunction; Hamilton Depression Rating Scale and Hamilton Anxiety Scale to assess for depression and anxiety, respectively; and brain MRI/MRA to detect any changes in subclinical cases. Results The mean age was 31.7 years. Twelve (40%) patients had positive antiphospholipid (aPL) antibodies with or without clinically evident antiphospholipid syndrome, 22 (73.33%) had different NP manifestations, 13 (43.3%) depression, 15 (50%) anxiety, and 16 (53.3%) cognitive dysfunction. All patients with depression and anxiety and 87.5% of patients with dementia showed abnormalities on MRI. All patients with positive aPL showed abnormalities on MRI, whereas abnormalities on MRI were found in only eight patients with SLE with negative aPL (100 vs. 44.4%). There was a significant correlation between SLE disease activity and both NP manifestations and abnormalities on MRI/MRA, and also between aPL antibodies and NP manifestations. Abnormalities on MRI included discrete white matter lesions, cortical atrophy, and gross infarctions. Conclusion Significant number of patients with SLE without overt NP manifestations had subclinical cerebrovascular and cognitive dysfunctions, depression, and anxiety by simple bedside questionnaires. SLE disease activity positively correlates with NP manifestations. The presence of aPL antibodies is a strong risk factor for developing NP SLE. Several distinct brain MRI patterns were observed in patients with active NP SLE, suggestive of different pathogenic mechanisms

Rheumatological manifestations in patients with malignancies: Relation to immune modulation therapy

Background: The relation between malignancies and rheumatic diseases (RDs) is complex with commonly shared symptoms. Rheumatological manifestations of malignancies may present as paraneoplastic syndromes and could follow chemotherapy. Aim of the work: to investigate rheumatic manifestations of patients with hematologic or solid malignancies and the relation to immune-modulation therapy. Patients and methods: The study included 25 patients with hematological and another 25 with solid malignancies. Patients were subjected to medical history, recording medications received, musculoskeletal examination and laboratory assessment. Results: The mean age and F:M of patients with hematological (43.7 ± 16.04 y and F:M 1.5:1) was significantly lower than those with solid (53.6 ± 14.3 y and F:M 7.3:1) malignancies (p = 0.025 and p = 0.024). Rheumatological manifestations as the first presentation was significantly higher in patients with haematological (60%) compared to solid (20%) malignancies (p = 0.004). Articular involvement was the commonest rheumatological manifestation (72%) followed by mucocutaneous (18%), oral/genital ulcers (10%), thromboembolic events (10%), Raynauds (8%), dry eyes (8%), myositis (6%) and myalgia (4%). The total leucocytic count and serum uric acid were significantly lower in patients with solid tumors (p = 0.045 and p = 0.026 respectively) and autoimmune markers were similar. Dry eye (16.7%), oral/genital ulcers (20.8%) and Raynaud‘s (16.7%) was present only in patients receiving anti-cancer treatment (n = 24). Paradoxically, arthritis was more frequent in those not receiving chemotherapy (n = 17) while myalgia (25%) was evident in those receiving checkpoint inhibitors (n = 8). Conclusion: Rheumatological manifestations occur with solid and hematological malignancies before or throughout the disease course and the most frequent was articular. Myalgia was associated with checkpoint inhibitors