Dataset Information

Crossreactive autoantibodies directed against cutaneous and joint antigens are present in psoriatic arthritis.

ABSTRACT: Psoriatic arthritis (PsA) is a chronic inflammatory disease of unknown origin, characterized by erosions and new bone formation. Diagnosis of PsA is mainly clinical and there are no biomarkers available. Moreover in PsA autoantibodies have not been described so far. Indeed an autoimmune origin has been suggested but never proven. Aim of the study was to investigate the possible presence of autoantibodies typically associated with PsA.We used pooled IgG immunoglobulins derived from 30 patients with PsA to screen a random peptide library in order to identify disease relevant autoantigen peptides.Among the selected peptides, one was recognised by nearly all the patients' sera. The identified peptide (PsA peptide: TNRRGRGSPGAL) shows sequence similarities with skin autoantigens, such as fibrillin 3, a constituent of actin microfibrils, desmocollin 3, a constituent of the desmosomes and keratin 78, a component of epithelial cytoskeleton. Interestingly the PsA peptide shares homology with the nebulin-related anchoring protein (N-RAP), a protein localized in the enthesis (point of insertion of a tendon or ligament to the bone), which represents the first affected site during early PsA. Antibodies affinity purified against the PsA peptide recognize fibrillin, desmocollin, keratin and N-RAP. Moreover antibodies directed against the PsA peptide are detectable in 85% of PsA patients. Such antibodies are not present in healthy donors and are present in 13/100 patients with seroposive rheumatoid arthritis (RA). In seronegative RA these antibodies are detectable only in 3/100 patients.Our results indicate that PsA is characterized by the presence of serum autoantibodies crossreacting with an epitope shared by skin and joint antigens.

SUBMITTER: Dolcino M

PROVIDER: S-EPMC4267814 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Crossreactive autoantibodies directed against cutaneous and joint antigens are present in psoriatic arthritis.

Dolcino Marzia M Lunardi Claudio C Ottria Andrea A Tinazzi Elisa E Patuzzo Giuseppe G Puccetti Antonio A

PloS one 20141216 12

<h4>Background</h4>Psoriatic arthritis (PsA) is a chronic inflammatory disease of unknown origin, characterized by erosions and new bone formation. Diagnosis of PsA is mainly clinical and there are no biomarkers available. Moreover in PsA autoantibodies have not been described so far. Indeed an autoimmune origin has been suggested but never proven. Aim of the study was to investigate the possible presence of autoantibodies typically associated with PsA.<h4>Methods</h4>We used pooled IgG immunogl ...[more]

PMID: 25514237

Similar Datasets

Project description:Anti-citrullinated-peptide antibodies (ACPA) have been detected in individuals with developing rheumatoid arthritis (RA) before the onset of symptom, with an initially limited spectrum of reactivities that gradually broadens. The aim was to analyze the evolution of ACPA response pre-dating symptom onset, using four selected citrullinated exogenous and endogenous antigens.A cohort of 521 individuals sampled before symptoms of RA appeared and 272 population controls were identified from the Biobank of Northern Sweden; 241 samples from patients with early RA were also collected. ACPA were detected by ELISA on viral citrullinated peptides (VCP) derived from Epstein-Barr-virus nuclear antigen (EBNA)1 and EBNA2 (VCP1 and VCP2) and histone-4-derived citrullinated peptides (HCP1 and HCP2).In pre-symptomatic individuals vs. patients with early RA, anti-VCP1 antibodies were detected in 10.4 % vs. 36.1 %, anti-VCP2 in 17.1 % vs. 52.3 %, anti-HCP1 in 10.2 % vs. 37.3 %, and anti-HCP2 in 16.3 % vs. 48.5 %, respectively. Anti-VCP and anti-HCP concentrations were significantly increased in pre-symptomatic individuals vs. controls (p?<?0.001) and were increased approaching symptom onset. Anti-VCP and anti-HCP appeared simultaneously (median (IQR) 5.3 (6) years before symptom onset) and in combination yielded a high-risk ratio for disease development (OR?=?8.0-18.9). Anti-VCP2 and anti-HCP2 antibodies were associated with HLA-DRB1*0401 in pre-symptomatic individuals. Three peptidylarginine deiminase (PAD)I3/PADI4 single nucleotide polymorphisms (SNPs) were significantly associated with anti-HCP1.Anti-VCP and anti-HCP antibodies pre-date symptom onset and predict disease development, but no hierarchy of citrullinated epitopes can be identified. These results suggest that no inciting citrullinated antigen so far described is common to all patients with RA. The association between PADI3/PADI4 polymorphism and anti-HCP1 antibodies suggests a novel link between deimination and production of ACPA.

Project description:BackgroundAutoimmune thyroid disease (AITD), which is characterized by an increased presence of thyroid autoantibodies (TAbs), such as antibodies against thyroid peroxidase (TPOAbs) and antibodies against thyroglobulin (TgAbs), has been reported to be associated with rheumatoid arthritis (RA) because AITD and RA both involve autoimmunity. However, few data are available on the incidence of TAbs in Chinese RA patients, and studies on the association between TAbs and joint damage as well as synovitis in RA patients remain sparse. Here, we aimed to evaluate the incidence of TAbs in a consecutive Chinese RA cohort and to investigate whether the elevated presence of TAbs is associated with joint damage and synovitis in RA patients.MethodsA total of 125 hospitalized RA patients were consecutively recruited. Clinical data and available synovial tissues were collected at baseline, and TAbs and thyroid function were detected by chemiluminescent immunoassay. Patients who tested positive for TPOAbs or TgAbs were classified as the TAbs-positive group, and patients who tested positive for neither TPOAbs nor TgAbs were recruited as the TAbs-negative group. Disease activity was assessed using DAS28-ESR (the disease activity score in 28 joints and including the erythrocyte sedimentation rate). X-ray assessment of the hand/wrist was performed according to the Sharp/van der Heijde-modified Sharp score (mTSS), and patients with an mTSS score >10 were defined as having radiographic joint damage (RJD). Serial tissue sections were stained immunohistochemically for CD3, CD15, CD20, CD34, CD38, and CD68, and synovitis were assessed according to Krenn's synovitis score.ResultsA total of 44 (35%) patients were positive for either TPOAbs or TgAbs. Importantly, there was a significantly greater percentage of patients with RJD in the TAbs-positive group versus the TAbs-negative group (68% vs. 42%, p = 0.005). Compared with the TAbs-negative group, significantly more CD38-positive plasma cells infiltrated the TAbs-positive synovium, and a higher percentage of patients with high-grade synovitis were observed in the TAbs-positive group (5/8, 63% vs. 5/14, 36%). Moreover, RF positivity and disease activity indicators, including TJC28, DAS28-ESR, and CDAI, were significantly higher in the TAbs-positive group (all p < 0.05). Adjusted logistic regression analysis revealed that positive TAbs (OR 2.999, 95% CI [1.301-6.913]; p = 0.010) and disease duration (OR 1.013, 95% CI [1.006-1.019]; p < 0.001) were independently associated with RJD, and an odds ratio of 2.845 (95% CI [1.062-7.622]) was found for RJD in women with positive TAbs (n = 37) compared with those without TAbs (n = 59) (p = 0.038).ConclusionOur data showed that joint destruction was amplified in RA patients with an elevated presence of TAbs, which supports the importance and necessity of TAbs and thyroid function screening and monitoring in RA patient management in clinical practice.

Dataset Information

Crossreactive autoantibodies directed against cutaneous and joint antigens are present in psoriatic arthritis.

Publications

Crossreactive autoantibodies directed against cutaneous and joint antigens are present in psoriatic arthritis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets