Effect of Etanercept on anti-carbamylated protein antibodies in patients with rheumatoid arthritis

Rheumatoid Arthritis (RA) is a systemic, chronic inflammatory disease characterized by inflammation of synovial joints and production of autoantibodies such as Rheumatoid Factor and antibodies directed against modified proteins - i.e. anti-citrullinated peptides antibody (ACPA). Carbamylation, as a post translational modification, has been recently associated to RA since anti-carbamylated protein antibodies (anti-CarP) have been detected in the sera of RA patients. The effect of treatment on anti-CarP level has been never addressed before. Through this study we aimed to investigate the short term effect of anti-TNF treatment with Etanercept on anti-CarP. We enrolled consecutive RA patients before starting treatment with Etanercept. Clinical data and serum samples were gathered from each patient at baseline and after 3 months of treatment. Disease activity was assessed at baseline and after 3 months by using the C-reactive protein - Disease Activity Score (DAS) 28. Sixty-three age and sex matched healthy donors served as controls. Anti-Car-P antibodies were investigated by immune-enzymatic assay. We enrolled 17 RA patients (F:M 15:2, mean age 44.1 ± 10.7 years, mean disease duration 7.9 ± 5.8 years). Six patients (35.3%) were positive for anti-CarP antibodies at baseline while three months after only 4 patients (23.5%) remained positive. Mean serum level of anti-CarP antibodies at baseline and after 3 months were: 253.0 ± 139.8AU/ml and 271.0 ± 132.4AU/ml respectively. Considering the persistently anti-CarP positive patients, the mean antibody titre increases from 386.2 ± 49.3AU/ml at baseline to 421.8 ± 144.0AU/ml at follow up. The effect of anti-TNF treatment on autoantibody status is still controversial; in particular, data on ACPA variation during treatment are discordant. In our cohort of long standing RA patients, a short term course of Etanercept did not affect the anti-CarP status. In conclusion, this pilot study demonstrated a slight reduction in the percentage of anti-CarP positive patients but an overall increase of antibody titres unrelated to the clinical response to TNF blockade was observed

Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the antidsDNA status. Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM). Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was signifiantly more frequent in anti-dsDNA + (30.2%), compared with antidsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.; = 0.001). Serositis resulted signifiantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.; < 0.0001). Th reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with antidsDNA − (21.8%, = 0.005). We did not identify significant differences in the mean ECLAM values before and after modifiation of anti-dsDNA status ( = 0.7). Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity

Oral mucosal lesions in electronic cigarettes consumers versus former smokers

Electronic cigarettes (ECs) have become very popular in recent years. However, many uncertainties remain about their side effects. This study aims to evaluate the prevalence and characteristics of oral mucosal lesions (OMLs) in former smokers compared to ECs consumers

Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients

BACKGROUND: Rheumatoid arthritis (RA) patients carry a high risk of cardiovascular morbidity and mortality. The excess of cardiovascular disease cannot be entirely explained by traditional risk factors and the immune system contributes to the development of atherosclerosis. Moreover, post-translational modifications such as citrullination and carbamylation have been linked to inflammation and atherosclerosis. Anti-carbamylated proteins antibodies (anti-CarP) are a new subset of autoantibodies identified in RA patients. This study aimed to investigate a possible association between anti-CarP and subclinical atherosclerosis in RA patients. METHODS: We enrolled RA patients and normal healthy controls (NHS) without known cardiovascular risk factors or heart disease. Cardiovascular risk was assessed using the Modified Systemic Coronary Risk Evaluation (mSCORE). Anti-CarP were investigated by a solid phase "home-made" ELISA. Anti-citrullinated protein antibodies (ACPA) and Rheumatoid Factor (RF) were investigated by ELISA assays. Subclinical atherosclerosis was evaluated by brachial artery Flow-Mediated Dilatation (FMD) and Carotid Intima-Media Thickness (c-IMT) while arterial stiffness by Ankle-Brachial Index (ABI) and Cardio-Ankle Vascular Index (CAVI). RESULTS: We enrolled 50 RA patients (34 F and 16 M, mean age 58.4 ± 13.1 years, mean disease duration 127 ± 96.7 months) and 30 age and sex matched NHS. According to the mSCORE, 58% of patients had a low risk, 32% a moderate and 8% a high risk for cardiovascular disease. FMD was significantly lower in RA patients than in NHS (5.6 ± 3.2 vs 10.7 ± 8.1%; p < 0.004) and CAVIs significantly higher in a RA patients compared to NHS (left CAVI 8.9 ± 1.7 vs 8.1 ± 1.5; p < 0.04 for and right CAVI 8.8 ± 1.6 vs 8.0 ± 1.4; p < 0.04 for the). ABI and c-IMT did not differ between the two populations. The multivariate regression analysis showed a significant association of anti-CarP antibodies with FMD, left and right CAVI and both c-IMT (r = 1.6 and p = 0.05; r = 1.7 and p = 0.04; r = 2.9 and p = 0.05; r = 1.5 and p = 0.03; r = 1.1 and p = 0.03 respectively). CONCLUSIONS: This study confirms that RA patients, without evidence of cardiovascular disease or traditional risk factors, have an impaired endothelial function. Moreover, we found an association with anti-CarP antibodies suggesting a possible contribution of these autoantibodies to endothelial dysfunction, the earliest stage of atherosclerosis. Besides ultrasound assessment, anti-CarP should be assessed in RA patients and considered an additional cardiovascular risk factor

Mucosa-Environment Interactions in the Pathogenesis of Rheumatoid Arthritis

Mucosal surfaces play a central role in the pathogenesis of rheumatoid arthritis (RA). Several risk factors, such as cigarette smoking, environmental pollution, and periodontitis interact with the host at the mucosal level, triggering immune system activation. Moreover, the alteration of microbiota homeostasis is gaining increased attention for its involvement in the disease pathogenesis, modulating the immune cell response at a local and subsequently at a systemic level. Currently, the onset of the clinical manifest arthritis is thought to be the last step of a series of pathogenic events lasting years. The positivity for anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), in absence of symptoms, characterizes a preclinical phase of RA namely systemic autoimmune phase- which is at high risk for disease progression. Several immune abnormalities, such as local ACPA production, increased T cell polarization towards a pro-inflammatory phenotype, and innate immune cell activation can be documented in at-risk subjects. Many of these abnormalities are direct consequences of the interaction between the environment and the host, which takes place at the mucosal level. The purpose of this review is to describe the humoral and cellular immune abnormalities detected in subjects at risk of RA, highlighting their origin from the mucosa environment interaction

Cognitive dysfunction improves in systemic lupus erythematosus: Results of a 10 years prospective study

Objective Cognitive impairment (CI) has been described in 3–80% of Systemic lupus erythematosus (SLE) patients but only short-term studies evaluated its over-time changes, suggesting that CI is usually a stable finding. We aimed at evaluating the changes of SLE-related CI in a 10-years prospective single center cohort study. Methods We evaluated 43 patients (M/F 5/38; mean age = 45.7±10.1 years; mean disease duration = 230.8±74.3 months) at baseline (T0) and after 10 years (T1). A test battery designed to detect fronto-subcortical dysfunction across five domains (memory, attention, abstract reasoning, executive and visuospatial function) was administered. A global cognitive dysfunction score (GCD) was obtained and associated with clinical and laboratory features. Results Prevalence of CI was 20.9% at T0 and 13.9% at T1 (P = NS). This impairment was prevalently mild at T0 (55.5%) and mild or moderate at T1 (36.3% for both degrees). After 10 years, CI improved in 50% of patients, while 10% worsened. Impaired memory (P = 0.02), executive functions (P = 0.02) and abstract reasoning (P = 0.03) were associated with dyslipidemia at T0. Worsening of visuospatial functions was significantly associated with dyslipidemia and Lupus Anticoagulant (P = 0.04 for both parameters). Finally, GCD significantly correlated with chronic damage measured by SLICC/damage index at T0 (r = 0.3; P = 0.04) and T1 (r = 0.3; P = 0.03). Conclusions For the first time, we assessed CI changes over 10-years in SLE. CI improved in the majority of the patients. Furthermore, we observed an improvement of the overall cognitive functions. These results could suggest that an appropriate management of the disease during the follow-up could be able to control SLE-related CI

Oral mucosal lesions in teenagers: a cross-sectional study

Aim The aim of this study was to evaluate the distribution of oral mucosal lesions (OMLs) in a wide sample of adolescents. Methods A retrospective cross-sectional study was carried out examining all medical records of adolescents (aged 13-18 years) treated at the Dental Clinic of the University of Brescia (Italy) in the period from 2008 to 2014. Cases with OMLs were selected. Data regarding age, gender, type of OML, bad habits, systemic chronic diseases were collected. Results A total of 6.374 medical records (mean age 15.2+-1.7 years) were examined. We found 1544 cases (31.7%) of oral mucosal lesions; 36 different types of mucosal alterations were detected and the most frequent were: aphthous ulcers (18%), traumatic ulcerations (14.3%), herpes simplex virus (11%), geographic tongue (9.6%), candidiasis (5.5%), and morsicatio buccarum (4.7%). Papilloma virus lesions (1.7%), piercing-related lesions (4%), multiform erythema (0.13%), oral lichen planus (0.13%) and granular cell tumour (0.06%) were also diagnosed. Conclusions The prevalence of OMLs in adolescents are different from those in children and, in some conditions, it could increase with age

Low expression of estrogen receptor β in T lymphocytes and high serum levels of anti-estrogen receptor α antibodies impact disease activity in female patients with systemic lupus erythematosus

BACKGROUND: Current evidence indicates that estrogens, in particular 17β-estradiol (E2), play a crucial role in the gender bias of autoimmune diseases although the underlying molecular mechanisms have not yet been fully elucidated. Immune cells have estrogen receptors (ERs), i.e., ERα and ERβ, that play pro- and anti-inflammatory functions, respectively, and the presence of one estrogen receptor (ER) subtype over the other might change estrogen effects, promoting or dampening inflammation. In this study, we contributed to define the influences of E2 on T cells from female patients with systemic lupus erythematosus (SLE), a representative autoimmune disease characterized by a higher prevalence in women than in men (female/male ratio 9:1). Particularly, our aim was to evaluate whether alterations of ERα and ERβ expression in T cells from female SLE patients may impact lymphocyte sensitivity to E2 and anti-ERα antibody (anti-ERα Ab) stimulation interfering with cell signaling and display a direct clinical effect. METHODS: Sixty-one premenopausal female patients with SLE and 40 age-matched healthy donors were recruited. Patients were divided into two groups based on the SLE Disease Activity Index 2000 (SLEDAI-2K) (i.e., <6 and ≥6). ER expression was evaluated in T lymphocytes by flow cytometry, immunofluorescence, and Western blot analyses. Serum anti-ERα Ab levels were analyzed by enzyme-linked immunosorbent assay (ELISA). ER-dependent signaling pathways were measured by a phosphoprotein detection kit. RESULTS: Intracellular ERβ expression was significantly lower in T cells from patients with SLEDAI-2K ≥6 as compared with healthy donors and patients with SLEDAI-2K <6 and negatively correlated with disease activity. The expression of intracellular and membrane-associated-ERα was similar in SLE and control T cells. ER-dependent signaling pathways were activated in T cells from SLE patients with SLEDAI-2K ≥6, but not with SLEDAI-2K <6, when both membrane and intracellular ERs were stimulated by co-treatment with E2 and anti-ERα Abs. CONCLUSIONS: Our results demonstrate an altered ER profile in SLE patients, possibly contributing to SLE pathogenesis and interfering with clinical activity, and highlight the potential exploitation of T cell-associated ERβ as a biomarker of disease activity

Prevalence, sensitivity and specificity of antibodies against carbamylated proteins in a monocentric cohort of patients with rheumatoid arthritis and other autoimmune rheumatic diseases

Antibodies against carbamylated proteins (anti-CarP) have been recently identified in the sera of patients with rheumatoid arthritis (RA). The objective of the study was to evaluate the prevalence, sensitivity and specificity of anti-CarP compared to anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF), replicating the existing data in a large cohort of Italian patients with RA and extending the evaluation to other autoimmune rheumatic diseases (AIRDs)

Timetable for oral prevention in childhood--developing dentition and oral habits: a current opinion

As most of the etiologic factors of malocclusion are of genetic origin and thus cannot be prevented, environmental causative factors have become the focus for correction. Early interception of oral habits may be an important step in order to prevent occlusal disturbances in children. The identification of an abnormal habit and the assessment of its potential immediate and long-term effects on the dentition and potentially on the craniofacial complex should be made at an early stage. This paper focuses on the most common oral habits influencing dentofacial growth in childhood and management of these habits in the developing dentition