scholarly journals Role of Anti-Carbamylated Protein Antibodies Compared to Anti-Citrullinated Protein Antibodies in Indigenous North Americans With Rheumatoid Arthritis, Their First-Degree Relatives, and Healthy Controls

2016 ◽  
Vol 68 (9) ◽  
pp. 2090-2098 ◽  
Author(s):  
H. Koppejan ◽  
L. A. Trouw ◽  
J. Sokolove ◽  
L. J. Lahey ◽  
T. J. W. Huizinga ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Healthy Controls ◽  
North Americans ◽  
First Degree Relatives ◽  
Citrullinated Protein

scholarly journals Dysregulated microRNA expression in rheumatoid arthritis families—a comparison between rheumatoid arthritis patients, their first-degree relatives, and healthy controls

2020 ◽  
Author(s):  
Emma Renman ◽  
Mikael Brink ◽  
Lisbeth Ärlestig ◽  
Solbritt Rantapää-Dahlqvist ◽  
Kristina Lejon
Keyword(s):  
Rheumatoid Arthritis ◽  
Microrna Expression ◽  
Significant Trend ◽  
Healthy Controls ◽  
Altered Expression ◽  
First Degree Relatives ◽  
Key Points ◽  
Polymerase Chain ◽  
And Gender

Abstract Objective Recent studies have demonstrated an altered expression of certain microRNAs in patients with rheumatoid arthritis (RA) as well as their first-degree relatives (FDRs) compared to healthy controls (HCs), suggesting a role of microRNA in the progression of the disease. To corroborate this, a set of well-characterized RA families originating from northern Sweden were analyzed for differential expression of a selected set of microRNAs. Method MicroRNA was isolated from frozen peripheral blood cells obtained from 21 different families and included 26 RA patients, 22 FDRs, and 21 HCs. Expression of the selected microRNAs miR-22-3p, miR-26b-5p, miR-34a-3p, miR-103a-3p, miR-142-3p, miR-146a-5p, miR-155, miR-346, and miR-451a was determined by a two-step quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis including clinical variables was applied. Results Out of the nine selected microRNAs that previously have been linked to RA, we confirmed four after adjusting for age and gender, i.e., miR-22-3p (p = 0.020), miR-26b-5p (p = 0.018), miR-142-3p (p = 0.005), and miR-155 (p = 0.033). Moreover, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs. In addition, analysis of the effect of corticosteroid use showed modulation of miR-103a-3p expression. Conclusions We confirm that microRNAs seem to be involved in the development of RA, and that the expression pattern in FDR is partly overlapping with RA patients. The contribution of single microRNAs in relation to the complex network including all microRNAs and other molecules is still to be revealed. Key Points• Expression levels of miR-22-3p, miR-26b-5p, miR-142-3p, and miR-155 were significantly altered in RA patients compared to those in controls.• In first-degree relatives, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs.

miR-216a-5p Suppresses the Proliferation, Invasion and Migration of Fibroblast-Like Synoviocyte in Rheumatoid Arthritis by Targeting Zinc Finger and BTB Domain-Containing Protein 2 (ZBTB2)

2021 ◽  
Vol 11 (5) ◽  
pp. 896-902
Author(s):  
Jinwei Zhao ◽  
Ling Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Zinc Finger ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Healthy Controls ◽  
Invasion And Migration ◽  
Btb Domain ◽  
And Migration

MicroRNAs have been reported to be associated with the initiation and progression of rheumatoid arthritis (RA). miR-216a-5p, one of the miRNAs, is involved in cancer cell proliferation, invasion and migration. However, the role of miR-216a-5p in RA remains to be explored. The expressions of miR-216a-5p and zinc finger and BTB domain-containing protein 2 (ZBTB2) in fibroblast-like synoviocytes (FLS) of RA or healthy controls were detected by qRT-PCR and western blot analysis. Transfection of overexpressed and silenced miR-216a-5p were performed to explore the functional role of miR-216a-5p in RA-FLS. Cell Counting Kit-8 (CCK-8) assay and transwell assay were employed to assess cell proliferation and cell invasion, respectively. Moreover, luciferase reporter assay was executed to verify the combination of miR-216a-5p and ZBTB2. The results showed that miR-216a-5p expression in RA-FLS was downregulated than healthy controls. Overexpres-sion of miR-216a-5p inhibited RA-FLS cell proliferation, invasion and migration, while miR-216a-5p silencing revealed the opposite results. In addition, ZBTB2 was identified to be a direct target of miR-216a-5p in RA-FLS and its expression was higher than that in healthy controls. Rescue experiments revealed that ZBTB2 overexpression reversed the effects of miR-216a-5p on the proliferation, invasion and migration of RA-FLS. These data indicated the suppressive role of miR-216a-5p in RA-FLS via the regulation of ZBTB2, suggesting that miR-216a-5p and ZBTB2 may be the new targets for the treatment of RA.

scholarly journals The role of anti-citrullinated protein antibodies (ACPA) in the pathogenesis of rheumatoid arthritis

2017 ◽  
Vol 42 (4) ◽  
pp. 390-398 ◽  
Author(s):  
Weronika Kurowska ◽  
Ewa H. Kuca-Warnawin ◽  
Anna Radzikowska ◽  
Włodzimierz Maśliński
Keyword(s):  
Rheumatoid Arthritis ◽  
Citrullinated Protein

scholarly journals Increased Concentrations of Antibody-Bound Circulatory Cell-Free DNA in Rheumatoid Arthritis

2007 ◽  
Vol 53 (9) ◽  
pp. 1609-1614 ◽  
Author(s):  
Xiao-Yan Zhong ◽  
Ines von Mühlenen ◽  
Ying Li ◽  
Anjeung Kang ◽  
Anurag Kumar Gupta ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Animal Experiments ◽  
Basic Research ◽  
Healthy Controls ◽  
Serum Samples ◽  
Cell Free Dna ◽  
Free Dna ◽  
New Evidence

Abstract Background: Increased concentrations of cell-free DNA have been found in several disorders and have been interpreted as evidence of increased rates of cell death or turnover. Evidence from in vitro and animal experiments suggests that DNA may play a role in the pathogenesis of rheumatoid arthritis (RA). Methods: We measured cell-free DNA in plasma and serum from patients with RA and healthy controls by use of quantitative PCR for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA. We used protein G Sepharose™ bead adsorption of plasma and elution to isolate antibody-bound DNA. Results: In paired plasma and serum samples of 16 healthy controls the median GAPDH copies were 4500 genome equivalents (GE)/mL plasma (range 319–21 000) and in 26 RA patients 17 000 GE/mL plasma (2100–2 375 000, P = 0.0001). In the serum from normal controls the median GAPDH copies were 35 000 GE/mL (1700–239 000) and from RA patients 222 000 GE/mL (21 000–2 375 000, P = 0.004). A median of 81% of the cell-free DNA in RA was associated with antibody compared with 9% in healthy controls (P = 0.001). The concentrations of DNA did not vary with the type of therapy patients received. Conclusions: These results provide new evidence for a role of cell-free DNA-antibody complexes in the etiology of RA, suggest new avenues for basic research, and may prove to be relevant to diagnosis and assessment of therapy.

scholarly journals Association Between STAT4 rs7574865 Polymorphism and Rheumatoid Arthritis: Debate Unresolved

2018 ◽  
Vol 12 (1) ◽  
pp. 172-178
Author(s):  
Iman Tarakji ◽  
Wafa Habbal ◽  
Fawza Monem
Keyword(s):  
Rheumatoid Arthritis ◽  
Genetic Factors ◽  
Shared Epitope ◽  
Direct Sequencing ◽  
Healthy Controls ◽  
Asian Populations ◽  
Genotype Frequencies ◽  
Potential Impact ◽  
Acpa Status ◽  
Citrullinated Protein

Background: STAT4 rs7574865 polymorphism has been evidently associated with susceptibility to Rheumatoid Arthritis (RA) in European and Eastern Asian populations, whereas studies in other countries reported otherwise. Objective: We investigated the distribution of STAT4 rs7574865 polymorphism in a group of Syrian RA patients. Methods: Eighty-one RA patients and forty healthy controls were enrolled and STAT4 rs7574865 was genotyped by direct sequencing. RA patients were stratified according to Anti-Citrullinated Protein Antibodies (ACPA) status for analysis. Results: Minor T allele frequencies were 30.4%, 16.7%, and 23.8% in ACPA-positive RA patients, ACPA-negative RA patients, and healthy controls, respectively. No significant differences in STAT4 rs7574865 allele/genotype frequencies were found between ACPA-positive RA patients, ACPA-negative RA patients, and healthy controls (P>0.05). Conclusion: STAT4 rs7574865 TT genotype showed a potential impact on ACPA positivity in Syrian RA patients. However, STAT4 rs7574865 effect on RA onset and severity is minor compared to other genetic factors such as HLA-DRB1 shared epitope alleles.

Novel autoantibodies identified in ACPA-negative rheumatoid arthritis

2021 ◽  
pp. annrheumdis-2020-218460
Author(s):  
Ketian Li ◽  
Wenxiu Mo ◽  
Lijun Wu ◽  
Xunyao Wu ◽  
Cainan Luo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Diagnosis ◽  
Protein Microarray ◽  
Healthy Controls ◽  
Microarray Technology ◽  
Validation And Verification ◽  
Human Proteins ◽  
Diagnostic Values ◽  
Acpa Status ◽  
Citrullinated Protein

ObjectivesLack of effective biomarkers in anti-citrullinated protein antibody (ACPA)-negative rheumatoid arthritis (RA) impedes early diagnosis and treatment. This study aimed to identify novel autoantibodies in RA and verify their diagnostic values in ACPA-negative RA based on protein microarray technology.MethodsA total of 1011 sera from 559 RA (276 ACPA-positive and 283 ACPA-negative), 239 disease controls (DCs) and 213 healthy controls (HCs) were collected and sampled on two sequential microarrays and ELISA and western blot (WB) detection, for novel autoantibodies discovery, validation and verification, respectively. The high-density protein microarray printed with a broad spectrum of recombinant human proteins was first employed to screen candidate autoantibodies, then focused microarrays composed of candidate autoantigens were used for validation, followed by ELISA and WB to verify the presence of the most promising candidates in ACPA-negative RA.ResultsNine novel autoantibodies were identified by two sequential microarrays with positivity 17.93%–27.59% and specificities >90% in ACPA-negative RA. Among these, anti-PTX3 and anti-DUSP11 autoantibodies presented with the highest sensitivity and were consistently verified by ELISA and WB. Pooling samples of all cohorts, the positivities of anti-PTX3 and anti-DUSP11 in ACPA-negative RA were 27.56% and 31.80%, respectively, similar to those in ACPA-positive RA, and significantly higher than in HCs (4.69% and 2.35%) and DCs (10.04% and 8.49%) (p<0.0001). Combination of anti-PTX3 with anti-DUSP11 significantly increased the diagnostic sensitivity (38.00%) with specificity of 88.72%, regardless of ACPA status.ConclusionAnti-PTX3 and anti-DUSP11 autoantibodies are newly identified biomarkers for diagnosis of ACPA-negative RA.

scholarly journals Cytokines of the Th1 and Th2 type in sera of rheumatoid arthritis patients; correlations with anti-Hsp40 immune response and diagnostic markers.

2010 ◽  
Vol 57 (3) ◽  
Author(s):  
Stefan Tukaj ◽  
Agnieszka Kotlarz ◽  
Agnieszka Jóźwik ◽  
Zaneta Smoleńska ◽  
Ewa Bryl ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Healthy Controls ◽  
Flow Cytometric ◽  
Das 28 ◽  
Systemic Inflammatory Disease ◽  
Cytokine Levels ◽  
Shock Proteins ◽  
Cytometric Bead Array Assay ◽  
Inflammatory Effect

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease which affects approximately 1% of the population worldwide. Recent research on the role of heat shock proteins (Hsps) in RA development indicates that they may have pro- or anti-inflammatory effect, most probably via modulating cytokine secretion. We investigated type Th1 (INFγ, TNFα, IL-2) and type Th2 (IL-10, IL-6, IL-4) cytokine levels in sera of RA patients and healthy controls, using flow cytometric bead array assay, and searched for correlations between the cytokine levels and serum antibodies against bacterial (DnaJ) and human (Hdj1, Hdj2 and Hdj3) Hsp40 proteins, as well as clinical and laboratory parameters. The levels of all cytokines studied were significantly increased in RA patients; the highest increase relative to healthy controls (7-fold) was observed for IL-6 and its levels correlated positively with the antibodies directed to DnaJ and to the C-terminal domain of Hdj2, and with diagnostic parameters (DAS 28, Steinbrocker RTG criteria, ARA/7, ESR, TEN, SW and GH). INFγ levels correlated negatively with DAS 28, ESR, TEN and SW. No correlations were found for TNFα, IL-2 or IL-4. Our results support the hypothesis of Hsp40 involvement in RA as well as indicate that IL-6 serum level is a good marker of the RA activity.

AB0173 Role of Anti Citrullinated Protein Antibodies in Follow-Up and Radiographic Damage in A Group of Patients with Early Rheumatoid Arthritis

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 955.3-956
Author(s):  
C. Carrasco Cubero ◽  
E. Vergara Prieto ◽  
I. Alcalá Peña ◽  
J.L. Άlvarez Vega ◽  
J.M. Salazar Vallinas ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Radiographic Damage ◽  
Citrullinated Protein
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