The aim of the work was to examine whether abnormalities in the lipid profile that tocilizumab (TCZ), an anti-IL-6 receptor Ab, exerts in rheumatoid arthritis (RA) patients is related to changes in either proprotein convertase subtilisin/kexin-9 (PCSK9) serum concentrations or in serum cholesterol efflux capacity (CEC). TOCRIVAR is a one-year prospective clinical trial that analyzes the influence of TCZ on cardiovascular risk factors. Twenty-seven RA patients receiving TCZ (8 mg/kg IV/q4w) were assessed at baseline and weeks 12, 24, and 52. Disease activity indexes, adiposity composition, physical activity, serum CEC, PCSK9, and lipoproteins serum concentrations were assessed at every visit. Basal high-sensitivity C-reactive protein (hs-CRP) and disease activity were markedly reduced throughout one-year TCZ treatment. While initially total cholesterol and LDL cholesterol increased their plasma concentration, decreasing to basal afterwards, lipoprotein(a) was significantly lower than basal in all visits of the study. CEC increased after 24 week of treatment proportionally to hs-CRP reduction, and remained significantly higher after week 52 [median % change 32 (3–141), p=0.021]. Interestingly, variations in LDL cholesterol basal concentration along the one year of TCZ treatment correlated directly with changes of PCSK9 serum concentration (r=0.37, p=0.003). Basal abdominal adiposity, BMI, and physical activity remained stable during the study. Long-term TCZ-treated RA patients show an increment in CEC inversely proportional to hs-CRP reduction and changes in LDL cholesterol that might be explained, at least in part, by variations in PCSK9 plasma concentration. Overall, TCZ treatment produces a favorable qualitative net effect in terms of atherogenic implication in RA patients.

PurposeTo report a case of central retinal artery occlusion (CRAO) in a patient with biopsy-verified Wegener's granulomatosis (WG) with positive C-ANCA.MethodsA 55-year-old woman presented with a 3-day history of acute painless bilateral loss of vision; she also complained of fever and weight loss. Examination showed a CRAO in the left eye and angiographically documented choroidal ischemia in both eyes.ResultsThe possibility of systemic vasculitis was not kept in mind until further studies were carried out; methylprednisolone pulse therapy was then started. Renal biopsy disclosed focal and segmental necrotizing vasculitis of the medium-sized arteries, supporting the diagnosis of WG, and cyclophosphamide pulse therapy was administered with gradual improvement, but there was no visual recovery.ConclusionCRAO as presenting manifestation of WG, in the context of retinal vasculitis, is very uncommon, but we should be aware of WG in the etiology of CRAO. This report shows the difficulty of diagnosing Wegener's granulomatosis; it requires a high index of suspicion, and we should obtain an accurate medical history and repeat serological and histopathological examinations. It emphasizes that inflammation of arteries leads to irreversible retinal infarction, and visual loss may occur

Objective It is well established that patients with systemic sclerosis (SSc) have a disrupted lipid profile and an increased cardiovascular risk. Cholesterol efflux capacity (CEC), the ability of high-density lipoprotein (HDL)-cholesterol to accept cholesterol from macrophages, has been linked to cardiovascular events. The aim of this study was to establish whether CEC and lipid profile were impaired in SSc patients with respect to controls and whether these changes were associated with disease-related data. Methods Cross-sectional study encompassed 188 individuals: 73 SSc patients and 115 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. A multivariable analysis was performed to study the differences in CEC between patients and controls, and if SSc-related data could explain such differences. Results The multivariable analysis adjusted for demographic characteristics, cardiovascular risk factors, and lipid-related molecules showed that total cholesterol (beta coefficient: − 22 [95%CI – 37 to – 7], p = 0.004), triglycerides (beta coefficient: 24 [95%CI 2–47], p = 0.033), lipoprotein A (beta coefficient: 22 [95%CI 2–43], p = 0.033), and CEC (beta coefficient: – 6 [95%CI − 10 to – 2]%,p = 0.002) were significantly different between patients and controls. Skin thickness, as assessed by modified Rodnan skin score, was independently associated with a lower CEC (beta coefficient: – 0.21 [95%CI – 0.37 to – 0.05]%, p = 0.011) after multivariable adjustment. Conclusion SSc patients show an abnormal lipid profile with respect to controls including CEC. Skin thickness is independent and inversely associated with CEC in SSc patients.

IntroductionThe aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc).MethodsIn total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genotyped by using a predesigned TaqMan allele-discrimination assay technology. Meta-analysis was assessed to determine whether an association exists between the genetic variants and SSc or its main clinical subtypes.ResultsNo evidence of association between CD40 and CD40LG genes variants and susceptibility to SSc was observed. Similarly, no significant statistical differences were observed when SSc patients were stratified by the clinical subtypes, the serologic features, and pulmonary fibrosis.ConclusionsOur results do not suggest an important role of CD40 and CD40LG gene polymorphisms in the susceptibility to or clinical expression of SSc.

Objectives It has been suggested that resistance to insulin action is a feature that accompanies rheumatoid arthritis (RA), a disease where chronic inflammation predominates and classical triggers for insulin resistance (IR) like obesity and diabetes are absents. However, data regarding characterization of RA features associated with this insulin resistance (IR) are lacking. The aim of this study was to investigate how sensitivity to insulin and markers of beta cell dysfunction (proinsulin processing metabolites) are expressed in RA. Methods 101 non-diabetic RA patients and 99 non-diabetic sex and age-matched controls were included in this study. Insulin sensitivity function through homeostatic model assessment (HOMA2), and beta cell secretion through insulin, split and intact proinsulin, and C-peptide were assessed in both groups. We performed multiple regression analysis to compare IR between groups and to explore the relation between RA features and IR. Data were adjusted for glucocorticoids intake and for IR classical risk factors. Results RA patients compared to controls show higher HOMA-IR (logHOMA-IR, beta coefficient, 0.40 [95% CI 0.20-0.59], p=0.00). When this data was adjusted for glucocorticoids intake, non-on corticosteroid patients maintained a higher IR index (beta coef. 0.14 [95% CI 0.05-0.24], p=0.00). Current prednisone treatment was not associated with higher IR in the patients’ intragroup comparison (beta coef. 0.56 [1.13-1.19], p=0.22). Insulin processing signaling in RA patients showed impaired features via an elevated intact proinsulin levels (beta coef. 3.13 [0.81-5.44] pMol/L, p=0.03 for the comparison between patients and controls). Split proinsulin levels were also higher in RA patients (beta coef. 13.7 pmol/L [3.57-9.40], p=0.00) even adjusting for prednisone intake (beta coef. 2.66 pmol/L [95%CI 1.62-5.95] for non steroids RA patients when compared to controls). In multiple regression analysis, RA features (disease duration, rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, disease activity through HAQ and DAS28 scores, and current non-biologic disease modifying antirheumatic drug), when adjusted for sex, age and body mass index, were not associated with IR or insulin propeptides. Conclusions Beta cell signaling is impaired in non-diabetic and non-corticoids RA patients. Disclosure of Interest None Declared