Increased Production of the Soluble Tumor-Associated Antigens CA19-9, CA125, and CA15-3 in Rheumatoid Arthritis

Some tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected carcinoembryonic antigen (CEA; CD66) in the rheumatoid (RA) synovium. The production of CEA, CA19-9, CA125, and CA15.3, may be increased in patients with RA, scleroderma, lupus, and SjÖgren's syndrome (SS). Some of these TAAs contain sialylated carbohydrate motifs and they are involved in tumor-associated cell adhesion and metastasis. We assessed levels of TAAs in the sera of RA patients and healthy subjects. Serum TAA levels were correlated with disease markers including serum rheumatoid factor (RF), C-reactive protein (CRP), and anti-CCP antibody levels, DAS28, age disease duration. TAAs including CEA, CA15-3, CA72-4, CA125, and CA19-9, and neuron-specific enolase (NSE) were assessed by immunoassay in the sera of 75 patients with RA and 50 age- and sex-matched healthy controls. Normal upper limits for these TAAs were 3.4 Μg/L, 25 kU/L, 6.9 kU/L, 35 kU/L, 34 kU/L, and 16.3 Μg/L, respectively. There were significantly more RA patients showing abnormally high levels of CA125 (10.8% versus 7.1%), CA19-9 (8.1% versus 0%), and CA15-3 (17.6% versus 14.3%) in comparison to controls ( P < 0.05). The mean absolute serum levels of CA125 (23.9 ± 1.8 versus 16.8 ± 2.2 kU/L) and CA19-9 (14.2 ± 1.2 versus 10.5 ± 1.6 kU/L) were also significantly higher in RA compared to controls ( P < 0.05). Among RA patients, serum CEA showed significant correlation with RF ( r = 0.270; P < 0.05). None of the assessed TAAs showed any correlation with CRP, anti-CCP, DAS28, age or disease duration. The concentration of some TAAs may be elevated in the sera of patients with established RA in comparison to healthy subjects. CEA, CA19-9, CA125, and CA15-3 contain carbohydrate motifs and thus they may be involved in synovitis-associated adhesive events. Furthermore, some TAAs, such as CEA, may also correlate with prognostic factors, such as serum RF levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73224/1/annals.1422.037.pd

Suppression of dendritic cell maturation and T cell proliferation by synovial fluid myeloid cells from mice with autoimmune arthritis

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Non-MHC Risk Alleles in Rheumatoid Arthritis and in the Syntenic Chromosome Regions of Corresponding Animal Models

Rheumatoid arthritis (RA) is a polygenic autoimmune disease primarily affecting the synovial joints. Numerous animal models show similarities to RA in humans; some of them not only mimic the clinical phenotypes but also demonstrate the involvement of homologous genomic regions in RA. This paper compares corresponding non-MHC genomic regions identified in rodent and human genome-wide association studies (GWAS). To date, over 30 non-MHC RA-associated loci have been identified in humans, and over 100 arthritis-associated loci have been identified in rodent models of RA. The genomic regions associated with the disease are designated by the name(s) of the gene having the most frequent and consistent RA-associated SNPs or a function suggesting their involvement in inflammatory or autoimmune processes. Animal studies on rats and mice preferentially have used single sequence length polymorphism (SSLP) markers to identify disease-associated qualitative and quantitative trait loci (QTLs) in the genome of F2 hybrids of arthritis-susceptible and arthritis-resistant rodent strains. Mouse GWAS appear to be far ahead of rat studies, and significantly more mouse QTLs correspond to human RA risk alleles

Genetics: A new interpretation of genetic studies in RA

Understanding the genetics of rheumatoid arthritis (RA) is complex, multiple genes and environmental factors are involved. A new multicentre genetic study summarizes the fundamental gene polymorphisms, pathways and cell types that are related to RA and, based on this analysis, proposes new targets for RA drug treatments

Valproate treatment normalizes EEG functional connectivity in successfully treated idiopathic generalized epilepsy patients

Aim: To investigate the effect of chronic VPA treatment of EEG functional connectivity insuccessfully treated idiopathic generalized epilepsy (IGE) patients.Patients and methods: 19-channel waking, resting-state EEG records of 26 IGE patients wereanalyzed before treatment (IGE) and after the 90th day of treatment (VPA), in seizure-free condition.Three minutes of artifact-free EEG background activity (without epileptiform potentials)was analyzed for each patient in both conditions. A group of 26 age-matched healthy normativecontrol persons (NC) was analyzed in the same way. All the EEG samples were processed toLORETA (Low Resolution Electromagnetic Tomography) to localize multiple distributed sourcesof EEG activity. Current source density time series were generated for 33 regions of interest(ROI)in each hemisphere for four frequency bands. Pearson correlation coefficients (R) were computedbetween all ROIs in each hemisphere, for four bands across the investigated samples. Rvalues corresponded to intrahemispheric, cortico-cortical functional EEG connectivity (EEGfC).Group and condition differences were analyzed by statistical parametric network method.Main results: p < 0.05, corrected for multiple comparisons: (1) The untreated IGE group showedincreased EEGfC in the delta and theta bands, and decreased EEGfC in the alpha band (as comparedto the NC group); (2) VPA treatment normalized EEGfC in the delta, theta and alpha bands;and (3) degree of normalization depended on frequency band and cortical region.Conclusions: VPA treatment normalizes EEGfC in IGE patients