Anti-CCP2 Antibodies: An Overview and Perspective of the Diagnostic Abilities of this Serological Marker for Early Rheumatoid Arthritis

The literature of the last 4 years confirms that the anti-CCP2 test is a very useful marker for the early and specific diagnosis of rheumatoid arthritis (RA). The anti-CCP2 test is very specific for RA (95–99%) and has sensitivity comparable to that of the rheumatoid factor (70–75%). The antibodies can be detected very early in the disease and can be used as an indicator for the progression and prognosis of RA. In this review, these interesting properties and some future possibilities of this diagnostic test are discussed

Altered Activation of Innate Immunity Associates with White Matter Volume and Diffusion in First-Episode Psychosis

First-episode psychosis (FEP) is associated with inflammatory and brain structural changes, but few studies have investigated whether systemic inflammation associates with brain structural changes in FEP. Thirty-seven FEP patients (median 27 days on antipsychotic medication), and 19 matched controls were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular risk markers were measured at baseline and 2 months later. We collected T1-and diffusion-weighted MRIs with a 3 T scanner from the patients at baseline. We analyzed the association of psychosis-related inflammatory markers with gray and white matter (WM) volume using voxel-based morphometry and WM diffusion using tract-based spatial statistics with whole-brain and region-of-interest (ROI) analyses. FEP patients had higher CCL22 and lower TGFa, CXCL1, CCL7, IFN-alpha 2 and ApoA-I than controls. CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls. The association between inflammatory markers and FEP remained significant after adjusting for age, sex, smoking and BMI. We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment. Baseline CCL22 levels correlated negatively with WM volume and positively with mean diffusivity and radial diffusivity bilaterally in the frontal lobes in ROI analyses. Decreased serum lan association between circulating chemokine levels and WM in FEP patients. Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology. The results suggest that an altered activation of innate immunity may contribute to WM damage in psychotic disorders.evel of ApoA-I was associated with smaller volume of the medial temporal WM. In whole-brain analyses, CCL22 correlated positively with mean diffusivity and radial diffusivity, and CXCL1 associated negatively with fractional anisotropy and positively with mean diffusivity and radial diffusivity in several brain regions. This is the first report to demonstratePeer reviewe

The increased ability to present citrullinated peptides is not unique to HLA-SE molecules: arginine-to-citrulline conversion also enhances peptide affinity for HLA-DQ molecules

BACKGROUND: Presentation of citrullinated neo-epitopes by HLA-DRB1 molecules that carry the shared epitope (SE) sequence was proposed to explain the association between HLA and seropositive RA. Although it is shown that several HLA-DRB1-SE molecules display enhanced binding affinities for citrullinated ligands, the ability of other HLA molecules to present citrullinated epitopes has not been investigated in a systematic manner. To better understand the HLA-RA connection, we aimed to investigate if the enhanced capacity to present arginine-to-citrulline-converted peptides is unique for HLA-SE alleles. METHODS: We selected four HLA molecules (one HLA-DR and three HLA-DQ molecules) that could potentially prefer citrulline over arginine residues in specific pockets and in addition two HLA-SE alleles as a method validation control. The affinity of peptides containing arginine/citrulline residues at positions interacting with the various peptide-binding pockets was compared by HLA class II peptide affinity assays. RESULTS: Pocket 4 of HLA-DRB1*04:04 and -DRB1*04:05 displayed a preference for citrulline over arginine, a property found in other pockets as well. HLA-DRB1*03:01 did not display an enhanced affinity for peptides containing a citrulline. In contrast, several peptide-binding pockets of the analyzed HLA-DQ molecules showed enhanced affinities for citrulline compared to arginine residues: i.e., pockets 4, 6, 7, and 9 of HLA-DQ2 and pockets 1, 6, and 9 of HLA-DQ7 and HLA-DQ8. CONCLUSIONS: Arginine-to-citrulline conversion of peptides can also enhance the binding affinity for non-HLA-SE molecules. Hence the capacity to present citrullinated neo-epitopes is not confined to HLA-SE molecules, opening the possibility that also other HLA molecules could potentiate a possible breach of T cell tolerance toward citrullinated antigens

Anti-ccp antibodies: The past, the present and the future

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Predictors of total morbidity burden on days 3, 5 and 8 after cardiac surgery

BACKGROUND: Post-operative morbidity affects up to 36% of cardiac surgical patients. However, few countries reliably record morbidity outcome data, despite patients wanting to be informed of all the risks associated with surgery. The Cardiac Post-Operative Morbidity Score (C-POMS) is a new tool for describing and scoring (0-13) total morbidity burden after cardiac surgery, derived by noting the presence/absence of 13 morbidity domains on days 3, 5, 8 and 15. Identifying modifiable C-POMS risk factors may suggest targets for intervention to reduce morbidity and healthcare costs. Thus, we explored the association of C-POMS with previously identified predictors of post-operative morbidity. METHODS: A systematic literature review of pre-operative risk assessment models for post-operative morbidity was conducted to identify variables associated with post-operative morbidity. The association of those variables with C-POMS was explored in patients drawn from the original C-POMS study (n = 444). RESULTS: Seventy risk factors were identified, of which 56 were available in the study and 49 were suitable for analysis. Numbers were too few to analyse associations on D15. Thirty-three (67.3%) and 20 (40.8%) variables were associated with C-POMS on at least 1 or 2 days, respectively. Pre-operative albumin concentration, left ventricular ejection fraction and New York Heart Association functional class were associated with C-POMS on all days. Of the 16 independent risk factors, pre-operative albumin and haemoglobin concentrations and weight are potentially modifiable. CONCLUSIONS: Different risk factors are associated with total morbidity burden on different post-operative days. Pre-operative albumin and haemoglobin concentrations and weight were independently predictive of post-operative total morbidity burden suggesting therapeutic interventions aimed at these might reduce both post-operative morbidity risk and health-care costs in patients undergoing cardiac surgery