scholarly journals Genetic Factors of Predisposition and Clinical Characteristics of Rheumatoid Arthritis in Russian Patients

2021 ◽  
Vol 11 (6) ◽  
pp. 469
Author(s):  
Ekaterina A. Vetchinkina ◽  
Dmitry S. Mikhaylenko ◽  
Ekaterina B. Kuznetsova ◽  
Tatiana A. Deryagina ◽  
Ekaterina A. Alekseeva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Risk ◽  
Risk Groups ◽  
Clinical Criteria ◽  
Reactive Protein ◽  
Small Influence ◽  
Targeted Ngs ◽  
Next Generation Sequencing Ngs ◽  
Citrullinated Peptide ◽  
Generation Sequencing

Rheumatoid arthritis (RA) is a multifactorial disease caused by a genetic predisposition and environmental factors. Predisposing alleles of various genes have a relatively small influence on the disease risk when they appear separately, but in combination, they predispose an individual to RA development. We genotyped 125 patients with RA including 60 SNPs and sequenced coding part of six genes by next-generation sequencing (NGS) technology on a target panel (IAD177464_185). According to our data, the alleles HLA-DRB1*04, HLA-DRB1*01, HLA-B*27, PTPN22 (rs2476601), TNF (rs1800629), TPMT (rs2842934), and IL4 (rs2243250), and genotypes HLA-DRB1*04:04, HLA-DRB1*01:16, PTPN22 (rs2476601), TPMT (rs2842934), were significantly associated with the RA development. Associations with clinical criteria (DAS28-CRP, HAQ-DI, and CDAI) and biochemical factors were investigated. We have shown that the PADI4 genotypes (rs11203367, rs2240340, rs11203366, and rs874881) are significantly associated with the baseline levels of DAS28-CRP, HAQ-DI, and CDAI; genotypes IL23R (rs7530511) and TNFRSF1A (rs748004, rs2228144) with the level of anti citrullinated peptide antibodies (ACPA); the genotypes DHODH (rs3213422) and MTHFR (rs180113) with the concentration of C-reactive protein (CRP); and the genotypes IL2RA (rs2104286), IRAK3 (rs11541076), and IL4R (rs1801275) with the level of rheumatoid factor (RF). Application of targeted NGS panel contributes to expanded genotyping to identify risk groups among the RA patients.

scholarly journals Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Mónica Vázquez-Del Mercado ◽  
Lourdes Nuñez-Atahualpa ◽  
Mauricio Figueroa-Sánchez ◽  
Eduardo Gómez-Bañuelos ◽  
Alberto Daniel Rocha-Muñoz ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Risk ◽  
Cardiovascular Events ◽  
Tumor Necrosis ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Citrullinated Peptide ◽  
Necrosis Factor

The main cause of death in rheumatoid arthritis (RA) is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP) antibody levels with increased carotid intima-media thickness (cIMT) in RA patients.Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC) were studied. All groups were assessed for atherogenic index of plasma (AIP) and cIMT. Anti-CCP, C-reactive protein (CRP), and levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P<0.001). Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFαand IL-6 (P<0.01), and lower levels of high density lipoprotein cholesterol (HDL-c) (P=0.02). The cIMT correlated with levels of anti-CCP (r=0.513,P=0.001), CRP (r=0.799,P<0.001), TNFα(r=0.642,P=0.001), and IL-6 (r=0.751,P<0.001). In multiple regression analysis, cIMT was associated with CRP (P<0.001) and anti-CCP levels (P=0.03).Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events.

scholarly journals Tofacitinib Citrate for Ulcerative Keratitis in a Patient with Rheumatoid Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Philip B. Meadow ◽  
Jacqueline Nguyen ◽  
Keerthana Kesavarapu
Keyword(s):  
Rheumatoid Arthritis ◽  
Reactive Protein ◽  
Laboratory Values ◽  
Body Sensation ◽  
History Of ◽  
Blurry Vision ◽  
Citrullinated Peptide ◽  
Preservative Free ◽  
Ulcerative Keratitis ◽  
Normal Laboratory

Purpose.To report a case of a patient with rheumatoid arthritis (RA) treated with tofacitinib citrate.Methods.Observational case report.Results.A 59-year-old patient, with a history of rheumatoid arthritis, on methotrexate 10 mg PO qwk and IV abatacept 750 mg/month, presented with photosensitivity, foreign body sensation, pain, redness, and blurry vision of her right eye (RE). Visual acuity of the RE was 20/200 and 20/20 of the left eye (LE). The slit lamp examination of the RE revealed dryness, 2+ injection of the conjunctiva, and pericentral ulceration of the cornea with 20–30% stromal thinning, pannus, and diffuse punctate epithelial erosions. The anterior chamber appeared normal. Laboratory values revealed elevated levels of rheumatoid factor, anticyclic citrullinated peptide antibodies, and C-reactive protein. The patient was switched to tofacitinib citrate 5 mg PO b.i.d, underwent corneal gluing, and was given prednisone acetate 1% gt TID, polytrim gt TID, neomycin-polymyxin-dexameth gt QD, FreshKote lubricant 1.8% gt QID, moxifloxacin 0.5% gt QID, and preservative free artificial tears Q1H. Within one week, laboratory values normalized, symptoms diminished, and the cornea reepithelialized.Conclusion.RA can present with ulcerative keratitis. Tofacitinib citrate, steroids, and corneal gluing were found to halt the progression of keratolysis and promote reepithelialization.

scholarly journals The ICR96 exon CNV validation series: a resource for orthogonal assessment of exon CNV calling in NGS data

2017 ◽  
Vol 2 ◽  
pp. 35 ◽  
Author(s):  
Shazia Mahamdallie ◽  
Elise Ruark ◽  
Shawn Yost ◽  
Emma Ramsay ◽  
Imran Uddin ◽  
...  
Keyword(s):  
Sequencing Data ◽  
Targeted Next Generation Sequencing ◽  
Negative Results ◽  
Targeted Ngs ◽  
Predisposition Genes ◽  
Next Generation Sequencing Ngs ◽  
Ngs Data ◽  
Validation Series ◽  
Generation Sequencing ◽  
Dependent Probe

Detection of deletions and duplications of whole exons (exon CNVs) is a key requirement of genetic testing. Accurate detection of this variant type has proved very challenging in targeted next-generation sequencing (NGS) data, particularly if only a single exon is involved. Many different NGS exon CNV calling methods have been developed over the last five years. Such methods are usually evaluated using simulated and/or in-house data due to a lack of publicly-available datasets with orthogonally generated results. This hinders tool comparisons, transparency and reproducibility. To provide a community resource for assessment of exon CNV calling methods in targeted NGS data, we here present the ICR96 exon CNV validation series. The dataset includes high-quality sequencing data from a targeted NGS assay (the TruSight Cancer Panel) together with Multiplex Ligation-dependent Probe Amplification (MLPA) results for 96 independent samples. 66 samples contain at least one validated exon CNV and 30 samples have validated negative results for exon CNVs in 26 genes. The dataset includes 46 exon CNVs in BRCA1, BRCA2, TP53, MLH1, MSH2, MSH6, PMS2, EPCAM or PTEN, giving excellent representation of the cancer predisposition genes most frequently tested in clinical practice. Moreover, the validated exon CNVs include 25 single exon CNVs, the most difficult type of exon CNV to detect. The FASTQ files for the ICR96 exon CNV validation series can be accessed through the European-Genome phenome Archive (EGA) under the accession number EGAS00001002428.

scholarly journals The relationship of blood CDC42 level with Th1 cells, Th17 cells, inflammation markers, disease risk/activity, and treatment efficacy of rheumatoid arthritis

2021 ◽  
Author(s):  
Yongji Li ◽  
Wendi Yang ◽  
Feng Wang
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Treatment Efficacy ◽  
Th17 Cells ◽  
Immune Cell ◽  
Disease Risk ◽  
Th1 Cells ◽  
Clinical Role ◽  
Reactive Protein

Abstract Background Cell division control protein 42 (CDC42) is reported to be involved in multiple inflammation processes by regulating T cell differentiation, maintaining immune cell homeostasis, and altering their function, while no relevant studies explored its clinical role in patients with rheumatoid arthritis (RA). Therefore, this study aimed to explore the correlation of CDC42 with Th1 and Th17 cells and its association with disease risk, activity, and treatment outcomes of RA. Methods After the enrollment of 95 active RA patients and 50 healthy subjects (HC), their CDC42, Th1 cells, and Th17 cells were assayed by RT-qPCR and flow cytometry, accordingly. For RA patients only, CDC42 was also detected at W6, and W12 after treatment. The treatment response and remission status were evaluated at W12. Results Compared to HC, CDC42 was reduced (P < 0.001), while Th1 cells (P = 0.021) and Th17 cells (P < 0.001) were increased in RA patients. Besides, CDC42 was negatively correlated with Th17 cells (P < 0.001), erythrocyte sedimentation rate (ESR) (P = 0.012), C-reactive protein (P = 0.002), and disease activity score in 28 joints (DAS28) (P = 0.007), but did not relate to Th1 cells or other disease features (all P > 0.05) in RA patients. Furthermore, CDC42 was elevated during treatment in RA patients (P < 0.001). Moreover, CDC42 increment at W12 correlated with treatment response (P = 0.004). Besides, CDC42 elevation at W0 (P = 0.038), W6 (P = 0.001), and W12 (P < 0.001) also linked with treatment remission. Conclusion CDC42 has the potential to serve as a biomarker to monitor disease activity and treatment efficacy in patients with RA.

scholarly journals Heart Rate–corrected QT Interval Duration in Rheumatoid Arthritis and Its Reduction with Treatment with the Interleukin 6 Inhibitor Tocilizumab

2018 ◽  
Vol 45 (12) ◽  
pp. 1620-1627 ◽  
Author(s):  
Hitomi Kobayashi ◽  
Yasuyuki Kobayashi ◽  
Isamu Yokoe ◽  
Noboru Kitamura ◽  
Atsuma Nishiwaki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interleukin 6 ◽  
Qt Interval ◽  
Cardiac Repolarization ◽  
Matrix Metalloproteinase 3 ◽  
Reactive Protein ◽  
Response Measures ◽  
Qt Interval Duration ◽  
Citrullinated Peptide ◽  
Repolarization Abnormalities

Objective.Individuals with rheumatoid arthritis (RA) are at a heightened risk of sudden cardiac death, an outcome increased in those with prolongation of the corrected electrocardiographic QT interval (QTc). We compared QTc between patients with RA and demographically matched controls and studied the change in QTc after treatment with the interleukin 6 inhibitor tocilizumab (TCZ).Methods.Standard 12-lead electrocardiograms were obtained and QTc was measured in patients with RA at baseline and after 24 weeks of TCZ treatment, then compared with non-RA controls who were frequency-matched on age and sex. Indicators of the baseline QTc and predictors of change in QTc were studied using multivariable linear regression.Results.A total of 94 RA and 42 non-RA controls were studied. The average baseline QTc was 10 ms longer in the RA group vs controls (422 vs 412 ms, respectively; p < 0.001) and decreased to an average of 406 ms with treatment (p < 0.001). Baseline QTc was significantly and independently higher among those with anticyclic citrullinated peptide antibodies seropositivity, higher swollen joint counts, and higher levels of C-reactive protein (CRP) and matrix metalloproteinase 3. Each log unit decrease in CRP with treatment was associated with an average reduction in QTc of 2.9 ms (p = 0.002) after adjusting for age and baseline QTc. Clinical response measures were not associated with the change in QTc.Conclusion.The marked normalization of QTc observed with TCZ treatment, and its close parallel with CRP reduction, support the premise that systemic inflammation contributes to cardiac repolarization abnormalities in RA that may be amenable to treatment.

scholarly journals Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

2020 ◽  
Vol 21 (14) ◽  
pp. 4911 ◽  
Author(s):  
Dmitry S. Mikhaylenko ◽  
Marina V. Nemtsova ◽  
Irina V. Bure ◽  
Ekaterina B. Kuznetsova ◽  
Ekaterina A. Alekseeva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Candidate Gene ◽  
Genetic Variants ◽  
Disease Risk ◽  
Significant Proportion ◽  
Therapy Response ◽  
Risk Groups ◽  
Antirheumatic Therapy ◽  
Disease Case ◽  
The Impact

Rheumatoid arthritis (RA) is the most common inflammatory arthropathy worldwide. Possible manifestations of RA can be represented by a wide variability of symptoms, clinical forms, and course options. This multifactorial disease is triggered by a genetic predisposition and environmental factors. Both clinical and genealogical studies have demonstrated disease case accumulation in families. Revealing the impact of candidate gene missense variants on the disease course elucidates understanding of RA molecular pathogenesis. A multivariate genomewide association study (GWAS) based analysis identified the genes and signalling pathways involved in the pathogenesis of the disease. However, these identified RA candidate gene variants only explain 30% of familial disease cases. The genetic causes for a significant proportion of familial RA have not been determined until now. Therefore, it is important to identify RA risk groups in different populations, as well as the possible prognostic value of some genetic variants for disease development, progression, and treatment. Our review has two purposes. First, to summarise the data on RA candidate genes and the increased disease risk associated with these alleles in various populations. Second, to describe how the genetic variants can be used in the selection of drugs for the treatment of RA.

scholarly journals Next Generation Sequencing Identifies Five Novel Mutations in Lebanese Patients with Bardet–Biedl and Usher Syndromes

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1047 ◽  
Author(s):  
Lama Jaffal ◽  
Wissam H Joumaa ◽  
Alexandre Assi ◽  
Charles Helou ◽  
George Cherfan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Usher Syndrome ◽  
Bioinformatic Analysis ◽  
Next Generation ◽  
Novel Mutations ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Targeted Ngs ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Aim: To identify disease-causing mutations in four Lebanese families: three families with Bardet–Biedl and one family with Usher syndrome (BBS and USH respectively), using next generation sequencing (NGS). Methods: We applied targeted NGS in two families and whole exome sequencing (WES) in two other families. Pathogenicity of candidate mutations was evaluated according to frequency, conservation, in silico prediction tools, segregation with disease, and compatibility with inheritance pattern. The presence of pathogenic variants was confirmed via Sanger sequencing followed by segregation analysis. Results: Most likely disease-causing mutations were identified in all included patients. In BBS patients, we found (M1): c.2258A > T, p. (Glu753Val) in BBS9, (M2): c.68T > C; p. (Leu23Pro) in ARL6, (M3): c.265_266delTT; p. (Leu89Valfs*11) and (M4): c.880T > G; p. (Tyr294Asp) in BBS12. A previously known variant (M5): c.551A > G; p. (Asp184Ser) was also detected in BBS5. In the USH patient, we found (M6): c.188A > C, p. (Tyr63Ser) in CLRN1. M2, M3, M4, and M6 were novel. All of the candidate mutations were shown to be likely disease-causing through our bioinformatic analysis. They also segregated with the corresponding phenotype in available family members. Conclusion: This study expanded the mutational spectrum and showed the genetic diversity of BBS and USH. It also spotlighted the efficiency of NGS techniques in revealing mutations underlying clinically and genetically heterogeneous disorders.

scholarly journals New Challenges in Tumor Mutation Heterogeneity in Advanced Ovarian Cancer by a Targeted Next-Generation Sequencing (NGS) Approach

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 584 ◽  
Author(s):  
Marica Garziera ◽  
Rossana Roncato ◽  
Marcella Montico ◽  
Elena De Mattia ◽  
Sara Gagno ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Next Generation Sequencing ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Genetic Profile ◽  
Next Generation ◽  
Platinum Based Chemotherapy ◽  
Targeted Ngs ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Next-generation sequencing (NGS) technology has advanced knowledge of the genomic landscape of ovarian cancer, leading to an innovative molecular classification of the disease. However, patient survival and response to platinum-based treatments are still not predictable based on the tumor genetic profile. This retrospective study characterized the repertoire of somatic mutations in advanced ovarian cancer to identify tumor genetic markers predictive of platinum chemo-resistance and prognosis. Using targeted NGS, 79 primary advanced (III–IV stage, tumor grade G2-3) ovarian cancer tumors, including 64 high-grade serous ovarian cancers (HGSOCs), were screened with a 26 cancer-genes panel. Patients, enrolled between 1995 and 2011, underwent primary debulking surgery (PDS) with optimal residual disease (RD < 1 cm) and platinum-based chemotherapy as first-line treatment. We found a heterogeneous mutational landscape in some uncommon ovarian histotypes and in HGSOC tumor samples with relevance in predicting platinum sensitivity. In particular, we identified a poor prognostic signature in patients with HGSOC harboring concurrent mutations in two driver actionable genes of the panel. The tumor heterogeneity described, sheds light on the translational potential of targeted NGS approach for the identification of subgroups of patients with distinct therapeutic vulnerabilities, that are modulated by the specific mutational profile expressed by the ovarian tumor.

Evaluation of Selected Rheumatoid Arthritis Activity Scores for Office-based Assessment

2010 ◽  
Vol 37 (12) ◽  
pp. 2466-2468 ◽  
Author(s):  
MARY BETH SULLIVAN ◽  
CHRISTINE IANNACCONE ◽  
JING CUI ◽  
BING LU ◽  
KERRI BATRA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Duration ◽  
Office Setting ◽  
Reactive Protein ◽  
Patient Reported ◽  
Pairwise Correlations ◽  
Patient Reported Measures ◽  
Rheumatoid Arthritis Activity ◽  
Citrullinated Peptide

Objective.Patient-reported measures can quickly provide assessments of rheumatoid arthritis (RA) disease activity in the office setting and do not require a laboratory test or physician examination. The goal of our study was to establish the validity of patient-reported indices compared to the C-reactive protein-based Disease Activity Score (DAS28-CRP4).Methods.Baseline and 1-year followup DAS28-CRP4 data were obtained from 740 RA subjects and were compared to indices (MDHAQ, CDAI, RAPID, RADAI, GAS) according to cyclic citrullinated peptide (CCP) status and change at 1 year. Pairwise correlations were calculated for each index.Results.Among 740 subjects, mean age 57 years, disease duration 14 years, the CDAI (r = 0.84, Δ r = 0.80) and RAPID (r = 0.71, Δ r = 0.70) had the highest correlation with the DAS28-CRP4 scores at baseline and 1 year. These correlations were not influenced by CCP status, disease-modifying antirheumatic drug use, biologic use, or by disease duration.Conclusion.In RA, the CDAI and RAPID correlated well with the DAS28-CRP4. They may both be practical and informative in the care of patients in the office setting.

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