Search

Objective The presence of antibodies against cyclic citrullinated peptides has been demonstrated to precede the onset of symptoms of rheumatoid arthritis (RA) by several years. The aim of this study was to analyze antibodies against 10 citrullinated autoantigen-derived peptides for reactivity before the onset of RA symptoms. Methods A case-control study was conducted within the Medical Biobank of Northern Sweden. The study was performed in 409 individuals, 386 of whom donated 717 blood samples before the onset of symptoms of RA (pre-patients). The median period of time predating the onset of RA was 7.4 years. A total of 1,305 population-based control subjects were also studied. Antibodies to 10 citrullinated peptides, fibrinogen α573 (Fibα573), Fibα591, Fibβ36-52, Fibβ72, Fibβ74, α-enolase (citrullinated α-enolase peptide 1 [CEP-1]), triple-helical type II collagen peptide C1 (citC1III), filaggrin, vimentin 2-17 (Vim2-17), and Vim60-75, were analyzed using a microarray system. Results The fluorescence intensity of antibodies against Fibβ36-52, Fibβ74, CEP-1, citC1III, and filaggrin was significantly increased in pre-patients compared with controls ( P < 0.001). The levels of the earliest-detectable antibodies (Fibα591 and Vim60-75) fluctuated over time, with only a slight increase after the onset of disease. The frequency of antibodies against Fibβ36-52, CEP-1, and filaggrin increased gradually, reaching the highest levels before symptom onset. The frequency of a cluster of antibodies, citC1III, Fibα573, and Fibβ74, increased only slightly before the onset of symptoms but increased prominently after disease onset. The odds ratio for the development of RA in individuals expressing both CEP-1 and Fibβ36-52 antibodies (using data from samples obtained <3.35 years predating symptom onset) was 40.4 (95% confidence interval 19.8-82.3) compared with having either antibody alone. Conclusion Development of an immune response toward citrullinated peptides is initially restricted but expands with time to induce a more specific response, with levels, particularly those of antibodies against CEP-1, Fibβ36-52, and filaggrin, increasing during the predating time period closer to the onset of symptoms. [ABSTRACT FROM AUTHOR]

Objective Production of anti-citrullinated protein antibodies (ACPAs) is an important biomarker for rheumatoid arthritis (RA). We undertook this study to determine whether genetic factors (HLA-DRB1 alleles) are associated with extreme ACPA levels in individuals with ACPA-positive RA, and to ascertain whether there are any phenotypic characteristics associated with these subgroups of RA. Methods HLA-DRB1 allelic groups were genotyped in 1,073 ACPA-positive RA patients from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study. We found that 283 patients (26.4%) had high ACPA levels (defined as >1,500 units/ml using the Euro-Diagnostica anti-CCP2 test), while the rest of the patients had moderate ACPA levels and served as the comparison group. A replication group consisted of 235 RA patients. Results No significant differences in baseline disease activity were observed between patients with high and those with moderate ACPA levels. However, the HLA-DRB1*15 allele was associated with high ACPA levels ( P = 0.0002). A similar trend was detected in HLA-DRB1*15-positive patients in the replication cohort, with meta-analysis of the discovery and replication cohorts demonstrating an overall effect of HLA-DRB1*15 on development of high ACPA levels in both the discovery and replication cohorts ( P < 0.0001 by Mantel-Haenszel test with a fixed-effects model). Conclusion Our data indicate that HLA-DRB1*15 may promote the production of high ACPA levels. Due to the high value of ACPA level scores in the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA, the presence of HLA-DRB1*15 may, at least in part, contribute to fulfilling the criteria for RA. This illustrates the complex nature of the genetic regulation of ACPA levels. Additional mechanistic studies of the regulation of ACPAs and ACPA-positive RA are pending. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the potential contribution of sera from patients with polymyositis (PM) and patients with dermatomyositis on the activation of endothelial cells (ECs). The methods used and the results obtained by study are discussed. The study revealed that the activation of EC with intercellular adhesion molecule 1 (ICAM-1) expression could contribute in the development of myositis and interstitial lung disease (ILD) among patients with anti-Jo-1 autoantibodies.

The article presents a study on regulating the interferon-α production caused by RNA-containing immune complexes in plasmacytoid dendritic cells (PDC). It mentions the use of purified normal PDCs from peripheral blood mononuclear cells (PBMCs) which were cocultivated with other cells separated from systemic lupus erythematosus (SLE) patients. Results show that IFNα produced by PDCs in PBMC cultures was inhibited by monocytes while natural killing (NK) cells were stimulatory.

The article focuses on a study which determined the mechanisms underlying the impact of antigen-presenting lectin-like receptor complex (APLEC) on arthritis in congenic rats. The study also determined if sex effects occur and whether APLEC influences different types of arthritis and phenotypes other than susceptibility. It found that rat APLEC regulates autoimmunity and multiple phenotypes in arthritis.

The article presents a study on the sensitivity, specificity and prognostic value of determination of levels of antibodies against modified citrullinated vimentin (anti-MCV) as compared with antibodies against cyclic citrullinated peptides (anti-CCP) in an inception cohort of patients with early rheumatoid arthritis (RA). Results indicate that changes in anti-MCV level showed stronger correlation with changes in clinical parameters than did changes in anti-CCP level.

The article presents a study which aimed to determine whether genetic variants of the interferon regulatory factor 5 (IRF-5) and Tyk-2 genes are associated with rheumatoid arthritis (RA) by analyzing single-nucleotide polymorphisms (SNP) in IRF-5 and SNP in Tyk2 in a Swedish cohort of RA patients and controls. The results indicate that genetic variants of IRF5 contribute to a unique disease etiology and pathogenesis in anti-cyclic citrullinated peptide (anti-CCP)-negative RA.