scholarly journals Closing the gap in early diagnosis of autoimmune rheumatic diseases: discovery of novel biomarkers using high-density peptide microarrays

Author(s):  
Kirsten Heiss ◽  
Pedro Simonini ◽  
Renate Sekul ◽  
Volker Stadler
2015 ◽  
Vol 38 (6) ◽  
Author(s):  
Karsten Conrad ◽  
Nadja Röber ◽  
Sebastian Rudolph ◽  
Michael Mahler

AbstractDespite the progress in the establishment of specific autoantibody assays, screening for antinuclear antibodies (ANA) by indirect immunofluorescence on HEp-2 cells for quality-oriented laboratory diagnosis of ANA associated rheumatic diseases (AARD) remains indispensable. Research results on the relevance of the dense fine speckled (DFS) pattern and DFS70 antibodies disclosed novel possibilities to optimize the serological stepwise diagnostics of AARD. The DFS pattern on HEp-2 cells is well differentiated from the classic “homogeneous” ANA pattern associated with dsDNA antibodies. In DFS pattern positive sera the most important detectable ANA specificity is the DFS70 antibody (synonym LEDGF antibody). This antibody is also the most frequent ANA specificity in ANA positive healthy persons. The prevalence of DFS70 antibodies in AARD patients is significantly lower compared with the prevalence in ANA-positive healthy individuals. There is a negative association between DFS70 antibodies and AARD, especially if no concomitant AARD-specific autoantibodies are found. Isolated DFS70 antibodies are detectable in <1% of AARD, but are detectable in 5%–11% of healthy individuals. In the presence of an isolated DFS70 antibody, the posttest probability for AARD is reduced significantly. DFS70 antibodies are valuable novel biomarkers for the improved interpretation of positive ANA but without detectable AARD associated autoantibodies and should be integrated in modified test algorithms to avoid unnecessary referrals and examinations of ANA-positive subjects.


2019 ◽  
Vol 20 (11) ◽  
pp. 1129-1140 ◽  
Author(s):  
Seyed Mostafa Parizadeh ◽  
Reza Jafarzadeh-Esfehani ◽  
Maryam Ghandehari ◽  
Fatemeh Goldani ◽  
Seyed Mohammad Reza Parizadeh ◽  
...  

Hepatocellular carcinoma (HCC) is a common cancer, and the second most common cause of cancer-associated death globally. One of the major reasons for this high rate of mortality is a failure to make an early diagnosis. The average survival in untreated HCC patients is estimated to be approximately three months. The 5-year overall survival rate after radical resection is about 15-40% and within two years, more than two third of patients experience a relapse. To date, the most common biomarker which has been used for the diagnosis of HCC is serum alpha-fetoprotein (AFP). However, there is a lack of sensitive and specific tumor biomarkers for the early diagnosis of HCC. MicroRNAs are a class of short endogenous RNA with crucial role in many biological activities and cellular pathways and can be found in various tissues and body fluids. The aim of this review was to summarize the results of recent studies investigating miRNAs as novel biomarkers for the early diagnosis and prognostic risk stratification of patients with this type of liver cancer.


Author(s):  
Manal Y. Tayel ◽  
Aida Nazir ◽  
Ibtessam M. Abdelhamid ◽  
Myriam A. S. Helmy ◽  
Nadia E. Zaki ◽  
...  

Abstract Background Chronic inflammation with sustained unregulated immune stimulation in autoimmune rheumatic diseases (ARD) may be a risk factor for developing lymphoproliferative disorders (LPD). Markers of ARD activity as high erythrocyte sedimentation rate or erosive joint diseases and the development of B-symptoms were accounted as risk factors for LPD development. We investigated the association of five inflammatory cytokine genes single nucleotide polymorphisms (SNPs): TNF-α -308G>A; TGF-β1 gene codon 10 T>C and 25 G>C; IL-10 promoter SNPs -1082 A>G, -819T>C, and -592A>C; IL-6 -174G>C; and IFN-γ 874 T>A with the risk of LPD development in ARD patients. The study was conducted on 70 patients divided into group I, 25 ARD patients diagnosed as RA (n = 15) and SLE (n = 10) and with no history of malignancy; group II, 25 patients diagnosed with LPD and had no ARD; and group III, 20 patients diagnosed with both diseases: ARD and LPD. Cytokine genotyping was analyzed by PCR-sequence-specific primer (PCR-SSP). Results ARD+LPD patients had significantly higher frequency of TNF-α -308A allele and AA+AG genotype (high TNF-α producers) and IL-10 -1082A allele and AA genotype (low IL-10 producers) than ARD patients (p = 0.003, p = 0.024, p = 0.003, p = 0.03, respectively) with a significantly increased risk of LPD development in ARD patients expressing the corresponding alleles and genotypes. No significant differences were detected in the distribution frequency of either TGF-β1, IL-6, or IFN-γ SNPs between groups I and III or any of the studied SNPs between groups II and III. The distribution frequency of IL-10 ATA haplotype was significantly increased in group III as compared to group I (p = 0.037). Conclusion The significantly increased frequency of the high-TNF-α- and low-IL-10-producing alleles and genotypes in ARD patients may participate in the provision of a proinflammatory milieu that eventually increases the risk of LPD development.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Maira Karabayas ◽  
James Brock ◽  
Gillian Fordyce ◽  
Neil Basu

Abstract Background/Aims  Leflunomide, a conventional disease modifying drug (csDMARD), is used in a variety of autoimmune rheumatic diseases (ARD) due to its immunomodulating, immunosuppressive and antiproliferative properties. This agent does however confer a greater infection risk and, due to its long half-life, drug washout procedures are often advised in the context of serious infections. Interestingly, Leflunomide is currently being tested as a potential therapy for COVID-19 in the general population. It is unknown whether leflunomide therapy is associated with a poor or favourable outcome among ARD patients infected with COVID-19. Methods  A Scottish-wide registry was rapidly developed in March 2020. Clinical characteristics and outcomes of infected cases were collated across all Scottish health boards. Eligible patients included any adult leflunomide treated ARD patients with a confirmed (clinically or PCR) diagnosis of COVID-19. Results  Of the 69 cases included in the registry, n = 4 were treated with leflunomide (75% female; mean age 61, SD 4.2). N = 2 were treated with combination baricitinib or hydroxychloroquine respectively, whilst n = 1 received recent corticosteroid therapy (intramuscular Kenalog). Comorbidities observed in this sub-cohort include diabetes mellitus n = 3, hypertension n = 2, cardiovascular disease n = 1, lung disease n = 1 and latent TB n = 1. At presentation, all patients (n = 4) experienced the established COVID-19 related symptom triad of dyspnoea, cough and fever and promptly developed acute respiratory syndrome. Diarrhoea was also recorded in n = 2 and constitutional upset n = 3. All patients suffered a serious COVID-19 disease outcome (defined as a requirement of invasive or non-invasive ventilation (n = 4) and/ or death (n = 2). P052 Table 1:Patient demographics, clinical characteristics and outcomesPatient 1Patient 2Patient 3Patient 4Age58635766SexFemaleFemaleMaleFemaleRheumatic diagnosisRheumatoid arthritisPsoriatic arthritisPsoriatic arthritisRheumatoid ArthritisComorbiditiesDiabetesHypertension Diabetes COPDNilIschaemic heart disease Hypertension Diabetes Latent TBClinical presentationDyspnoea Cough Fever Confusion Constitutional upsetDyspnoea Cough Fever Diarrhoea Constitutional upsetDyspnoea Cough Fever Constitutional upsetDyspnoea Cough Fever Diarrhoea Constitutional upsetAdditional csDMARD*NilNilNilHydroxychloroquinebDMARD**/ tsDMARD***BaricitinibNilNilNilSteroid therapyNilNilNilIM KenalogInvasive or non-invasive ventilationYesYesYesYesDeathNoNoYesYes* conventional disease modifying drug,**biologic disease modifying drug,***targeted synthetic disease modifying drug. Conclusion  Preliminary data from this Scotland-wide registry has identified only a small number of leflunomide treated ARD patients infected with COVID-19. However, it is concerning that all cases experienced a serious outcome. Given the relatively infrequent prescription of this drug, combining similar national registry data is necessary to ensure this observation is not spurious. If confirmed, leflunomide washout procedures should be encouraged among such patients when they first present with COVID-19. Disclosure  M. Karabayas: None. J. Brock: None. G. Fordyce: None. N. Basu: None.


2021 ◽  
Author(s):  
Cindy Orvain ◽  
Morgane Boulch ◽  
Philippe Bousso ◽  
Yannick Allanore ◽  
Jérôme Avouac

2015 ◽  
Vol 1 ◽  
pp. 3-8
Author(s):  
Brygida Kwiatkowska ◽  
Filip Raciborski ◽  
Anna Kłak ◽  
Maria Maślińska ◽  
Jerzy Gryglewicz

Rheumatology ◽  
2021 ◽  
Author(s):  
Jun Seok Park ◽  
Seulggie Choi ◽  
Kyuwoong Kim ◽  
Jooyoung Chang ◽  
Sung Min Kim ◽  
...  

Abstract Objective The primary objective is to investigate adverse effects of ambient particulate matter (PM) in various size on the incidence of prevalent autoimmune rheumatic diseases (AIRDs): Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), and Systemic Lupus Erythematosus (SLE). Methods We investigated 230,034 participants in three metropolitan cities of South Korea from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). Starting from January 2010, subjects were followed up until the first event of prevalent AIRDs, death, or December 2013. 2008-2009 respective averages of PM2.5 (&lt; 2.5μm) and PMcoarse (2.5μm to 10μm) were linked with participants’ administrative district codes. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis in one- and two-pollutant model. Results Adjusted for age, sex, region, and household income in two-pollutant model, RA incidence was positively associated with 10μg/m³ increment of PM2.5 (aHR = 1.74, 95% CI: 1.06-2.86), but not with PMcoarse (aHR = 1.27, 95% CI: 0.87-1.85). In one-pollutant model, an elevated incidence rate of RA was slightly attenuated (PM2.5 aHR = 1.61, 95% CI: 0.99-2.61; PMcoarse aHR = 1.13, 95% CI: 0.80-1.61), with marginal statistical significance of PM2.5. RA incidence was also higher in 4th quartile group of PM2.5 compared to 1st quartile group (aHR = 1.83, 95% CI: 1.07-3.11). No adverse effects of PM were found on AS or SLE in one- and two-pollutant models. Conclusion Important components of PM10 associated with RA incidence were fine fractions (PM2.5), while no positive association was found between PM and AS or SLE.


Sign in / Sign up

Export Citation Format

Share Document