scholarly journals Combining Calcitonin and Procalcitonin and Rheumatoid Arthritis-Related Biomarkers Improve Diagnostic Outcomes in Early Rheumatoid Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yingwen Liu ◽  
Jing Shi ◽  
Bo Wang ◽  
Lijing Zhou ◽  
Xiaolan Zhou ◽  
...  

Objective. To demonstrate whether procalcitonin (PCT) combined with calcitonin (CT) could provide additional diagnostic value to other clinically available rheumatoid arthritis- (RA-) related biomarkers in the early diagnosis of RA. Method. The blood samples aseptically collected by venipuncture were centrifuged within 1 hour and frozen at -80°C. PCT and CT levels were measured using electrochemiluminescence immunoassay (ECLIA) in 260 subjects (48 patients with early RA, 34 patients with established RA, 37 patients with systemic lupus erythematosus, 30 with osteoarthritis, 31 with gouty arthritis, and 80 healthy participants). Anti-cyclic citrullinated peptide (Anti-CCP) and anti-RA33 antibodies (Anti-RA33) were analyzed by ELISA. RF was detected by transmission immunoturbidimetry. Mann–Whitney U tests and Kruskal-Wallis tests compared differences among groups. Spearman’s rank correlation analysis determined the relationship between biomarkers. Receiver-operator characteristic (ROC) curves were generated, and diagnostic performance was assessed by area under the curve (AUC), as well as specificity, sensitivity, likelihood ratios (LR). Results. Median serum PCT concentrations were significantly higher ( p < 0.0001 ) in patients with early RA (0.065 ng/ml) when compared with healthy controls (0.024 ng/ml), and patients with osteoarthritis (0.025 ng/ml). When compared with gouty arthritis (GA) controls (0.072 ng/ml) and systemic lupus erythematosus (SLE) controls (0.093 ng/ml), median serum PCT concentrations were not significant in patients with early RA (0.065 ng/ml). Median serum CT concentrations were significantly lower ( p < 0.0001 ) in patients with early RA (0.880 pg/ml) compared with healthy controls (3.159 pg/ml), patients with SLE (2.480 pg/ml), and patients with GA (2.550 pg/ml). When compared with osteoarthritis controls (0.586 pg/ml), median serum CT concentrations were not significant in patients with early RA (0.880 pg/ml). ROC curve analysis comparing early RA with healthy controls demonstrated that the AUC of RF, anti-CCP, and anti-RA33 were 0.66, 0.73, and 0.64, respectively; the additions of PCT and CT further improved the diagnostic ability of early RA with the AUC of 0.97, 0.98, and 0.97, respectively ( p < 0.01 ). The sensitivities of RF, anti-CCP, and anti-RA33 for early RA were 33.33%, 44.74%, and 58.33%, respectively, and the additions of PCT and CT showed very high sensitivities of 83.33%, 92.11%, and 87.50%. The high-value groups of PCT moderately correlated with the anti-RA33 levels ( r = 0.417 , p < 0.05 ). CT had no significant correlation with disease duration, radiographic progression, or clinical/serological variables, such as ESR levels, CRP levels, RF, anti-CCP, and anti-RA33 levels in early RA. Conclusions. Serum PCT and CT combined with clinically available RA-related biomarkers could further improve the diagnostic efficiency of early RA.

Epigenomics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 973-988
Author(s):  
Gangqiang Guo ◽  
Aqiong Chen ◽  
Lele Ye ◽  
Huijing Wang ◽  
Zhiyuan Chen ◽  
...  

Aim: We aimed to identify differentially expressed Long noncoding RNAs (lncRNAs) and explore their functional roles in systemic lupus erythematosus (SLE). Materials & methods: We identified dysregulated lncRNAs and investigated their prognostic values and potential functions using MiRTarget2, catRAPID omics and Bedtools/blast/Pearson analyses. Results: Among the 143 differentially expressed lncRNAs, TCONS_00483150 could be used to distinguish patients with SLE from healthy controls and those with rheumatoid arthritis and patients with active/stable SLE from healthy controls. TCONS_00483150 was significantly correlated with anti-Rib-P antibody positivity and low C3 levels; TCONS_00483150 dysregulation might contribute to the metabolism of RNA and proteins in SLE patients. Conclusion: Overall, our findings offer a transcriptome-wide overview of aberrantly expressed lncRNAs in patients with SLE and highlight TCONS_00483150 as a potential novel diagnostic biomarker.


2019 ◽  
Vol 45 (04) ◽  
pp. 348-355
Author(s):  
Gao Zhao-wei ◽  
Guan-hua Zhao ◽  
Rui-cheng Li ◽  
Hui-ping Wang ◽  
Chong Liu ◽  
...  

Abstract Objective The aim of this study was to evaluate the changes and diagnostic value of serum ADA activity in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), and myasthenia gravis (MG). Methods Serum ADA activity, including total ADA (tADA) and its isoenzymes (ADA1 and ADA2), was determined in patients with different autoimmune diseases (144 RA, 114 SLE, 55 AS, 68 MG). The changes in serum ADA activity in patients were analysed. A receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic performance of serum ADA activity. Results Compared with healthy controls, the serum tADA activity in SLE patients was significantly increased (p<0.001), while the serum tADA activity in patients with RA, AS and MG did not change (p>0.05). The ROC analysis showed that the optimal cut-off value of serum tADA activity for SLE diagnosis was 10.5 U/L (79.8% specificity and 74.6% sensitivity; likelihood ratio (LR): 3.693; p<0.001). Moreover, our results showed that there were no significant changes of ADA1 and ADA2 activity in RA, AS and MG patients, while the serum ADA2 activity was significantly increased in SLE patients. The ROC analysis showed that ADA2 activity could be used in diagnosing SLE with 75.4% specificity and 78.1% sensitivity (LR: 3.175). Based on the ROC curve analysis, serum tADA activity (79.8% specificity and 74.6% sensitivity; likelihood ratio (LR): 3.693) and ADA2 activity (75.4% specificity and 78.1% sensitivity; LR: 3.175) are unlikely to be used in diagnosing SLE. Furthermore, there was a positive correlation between tADA activity and SLE disease activity (r=0.303, p=0.010). Notably, serum tADA activity in SLE patients with arthritis was higher than in patients without arthritis (p=0.005), which suggests that tADA activity might be related to lupus arthritis. Conclusion These findings suggest that serum tADA and ADA2 activity might play an important role in SLE progression.


2021 ◽  
Author(s):  
David A. Fox

The rheumatic diseases encompass a broad spectrum of conditions that include inflammatory, metabolic, and structural diseases of the joints and adjacent musculoskeletal structures, chronic musculoskeletal pain syndromes, and a wide range of systemic autoimmune and autoinflammatory diseases that may or may not have articular manifestations. This review contains 4 figures, 13 tables, and 28 references. Key Words osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, fibromyalgia, acute monoarthritis, Ankylosing spondylitis, nonradiographic axial spondyloarthritis, gouty arthritis, lupus nephritis


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Susan S. Copple ◽  
Troy D. Jaskowski ◽  
Rashelle Giles ◽  
Harry R. Hill

Objective.To evaluate NOVA View with focus on reading archived images versus microscope based manual interpretation of ANA HEp-2 slides by an experienced, certified medical technologist.Methods.369 well defined sera from: 44 rheumatoid arthritis, 50 systemic lupus erythematosus, 35 scleroderma, 19 Sjögren’s syndrome, and 10 polymyositis patients as well as 99 healthy controls were examined. In addition, 12 defined sera from the Centers for Disease Control and 100 random patient sera sent to ARUP Laboratories for ANA HEp-2 IIF testing were included. Samples were read using the archived images on NOVA View and compared to results obtained from manual reading.Results.At a 1 : 40/1 : 80 dilution the resulting comparison demonstrated 94.8%/92.9% positive, 97.4%/97.4% negative, and 96.5%/96.2% total agreements between manual IIF and NOVA View archived images. Agreement of identifiable patterns between methods was 97%, with PCNA and mixed patterns undetermined.Conclusion.Excellent agreements were obtained between reading archived images on NOVA View and manually on a fluorescent microscope. In addition, workflow benefits were observed which need to be analyzed in future studies.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1036.3-1036
Author(s):  
M. Kosturkova ◽  
G. Mihaylova ◽  
M. Radanova

Background:Complement is strongly implicated in the pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Its component C1q plays a dualistic role, triggering the inflammatory cascade on one hand and directing the clearance of immune complexes on the other. Homozygous genetic deficiency of C1q is strongly associated with SLE and SLE-like phenotype as almost 90% of C1q deficient individuals develop SLE or similar disease. Nevertheless, there are few and inconsistent studies exploring the single nucleotide polymorphisms (SNPs) of the C1q gene cluster in relation to the pathogenesis of SLE and RA.Objectives:The aim of the study was to evaluate the possible association of five SNPs – rs292001, rs172378, rs294179, rs665691 and rs682658 in complement C1q gene cluster with susceptibility to SLE and RA in Bulgarian cohort.Methods:Fifty patients with SLE, sixty-one patients with RA and sixty-seven healthy controls were genotyped for the five SNPs by TaqMan allelic discrimination assay.Results:Frequency of genotypes and alleles of rs294179, rs665691 and rs682658 SNPs was similar between patients with SLE, RA and healthy controls. For rs172378 SNP, the minor G allele (OR = 2.73; 95% CI, 1.59-4.67, p=0.0003) and GG genotype (OR = 5.12; 95% CI, 1.60-16.49, p=0.006) were associated with susceptibility to RA. In our cohort in accordance with others, AA rs292001 SNP genotype was associated with increased risk for RA (OR = 3.32; 95% CI, 1.19-9.20, p=0.021). For SLE patients, AA rs292001 SNP genotype was low presented and did not associate with disease.Conclusion:GG genotype of rs172378 SNP in C1q gene cluster could be considered as a new risk factor for RA.References:[1]Diane Scott et al (2016). The paradoxical roles of C1q and C3 in autoimmunity. Immunobiology, 719-25. doi:10.1016/j.imbio.2015.05.001.[2]Giles JL et al (2015). Functional analysis of a complement polymorphism (rs17611) associated with rheumatoid arthritis. J Immunol., 3029-34. doi:10.4049/jimmunol.1402956.[3]Holers, V. M. (2018). Complement in the Initiation and Evolution of Rheumatoid Arthritis. Frontiers in immunology, 1057. doi:10.3389/fimmu.2018.01057.[4]Lintner, K. E. (2016). Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases. Frontiers in immunology, 36. doi:10.3389/fimmu.2016.00036.[5]Lu, J. &. (2017). C1 Complex: An Adaptable Proteolytic Module for Complement and Non-Complement Functions. Frontiers in immunology, 592. doi:10.3389/fimmu.2017.00592.[6]Manderson, A. P. (2004). The role of complement in the development of systemic lupus erythematosus. Annual review of immunology, 431-456. doi:10.1146/annurev.immunol.22.012703.104549.[7]Martens, H. A. (2009). Analysis of C1q polymorphisms suggests association with systemic lupus erythematosus, serum C1q and CH50 levels and disease severity. Annals of the rheumatic diseases, 715–720. doi:10.1136/ard.2007.085688.[8]Namjou B, G.-M. C. (2009). Evaluation of C1q genomic region in minority racial groups of lupus. Genes Immun., 517-24. doi:10.1038/gene.2009.33.[9]Radanova M et al(2015). Association of rs172378 C1q gene cluster polymorphism with lupus nephritis in Bulgarian patients. Lupus, 280-9. doi:10.1177/0961203314555173.[10]Rafiq S et al (2010). Assessing association of common variation in the C1Q gene cluster with systemic lupus erythematosus. Clin Exp Immunol., 284-9. doi:10.1111/j.1365-2249.2010.04185.x.[11]Schejbel L et al (2011). Molecular basis of hereditary C1q deficiency-revisited: identification of several novel disease-causing mutations. Genes Immun., 626-634.[12]Trouw LA et al (2013). Genetic variants in the region of the C1q genes are associated with rheumatoid arthritis. Clin Exp Immunol., 76-83. doi:10.1111/cei.12097.[13]Trouw L. A. (2017). The complement system as a potential therapeutic target in rheumatic disease. Nature reviews. Rheumatology, 538–547. doi:10.1038/nrrheum.2017.125.[14]Walport M. J. (2002). Complement and systemic lupus erythematosus. Arthritis research, S279–S293. doi:10.1186/ar586.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1311.2-1311
Author(s):  
A. Mashayekhi Sardoo ◽  
P. Leo ◽  
M. Santos ◽  
T. Costa ◽  
S. F. Almeida ◽  
...  

Background:Early diagnosis of inflammatory rheumatic diseases (IRD), as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and axial Spondyloarthritis (axSpA) represents in our days a major clinical challenge. Increasing evidence has determined that early diagnosis, prompt treatment initiation and early achievement of remission are the best predictors of long-term clinical, functional and radiographic outcomes. Therefore, identification of sensitive biomarkers to support an early diagnosis to enable early therapy is of utmost importance [1,2].Objectives:This study aims to identify novel genes that may improve the current clinical diagnosis approach for early SLE, RA and axSpA.Methods:A cross-sectional study was conducted on 44 participants, 12 with axSpA (according to ASAS criteria), 11 with RA (according to ACR/EULAR criteria for RA), 10 with SLE (according to ACR classification criteria for SLE) and 11 Healthy Controls (HC), gender and age matched. Patients with co-occurrence of other IRD or having received biological therapies were excluded. Peripheral blood samples were collected into PAXgene tubes and stored in -80°C. mRNA profiling by RNA-seq was performed. Unpaired t-tests with multivariate permutation correction were applied to identify differentially expressed genes (DEGs) between patients and HC for each disease and within diseases. Enrichment analysis, Gene ontology (GO) and Kyoto Enrichment of Genes and Genomes (KEGG) analysis were also performed. DEGs that allow to distinguish each disease from HC and between diseases. The top DEGs (axSpA n=2, RA n=2, SLE n=3) identified were confirmed by quantitative RT-PCR.Results:For axSpA, genes involved in negative regulation of cytokines by JAK/STAT pathway and in osteoblast differentiation through STAT3 pathway, were confirmed. In SLE, genes involved in trap for immune complexes in peripheral blood and involved in nucleosome regulation, were also confirmed. Regarding RA, no genes were confirmed.Conclusion:Our work provides new insights into IRD pathogenesis, and discloses new biomarkers, which may be useful as either predictive biomarkers for diagnosis or therapeutic targets to improve IRD approach.Further validation are needed in different cohorts.References:[1]Monti, S. et al. (2015) ‘Rheumatoid arthritis treatment: The earlier the better to prevent joint damage’, RMD Open, 1(Suppl 1), pp. 1–5. doi: 10.1136/rmdopen-2015-000057.[2]Oglesby, A. et al. (2014) ‘Impact of early versus late systemic lupus erythematosus diagnosis on clinical and economic outcomes.’, Applied health economics and health policy, 12(2), pp. 179–90. doi: 10.1007/s40258-014-0085-x.Acknowledgments:To all patients and healthy controls who participated in the studyDisclosure of Interests:Atlas Mashayekhi Sardoo: None declared, Paul Leo: None declared, Mariana Santos: None declared, Tiago Costa: None declared, Sergio Fernandes Almeida: None declared, Sara Maia: None declared, Vladimir Benes: None declared, Mattew Brown Speakers bureau: MSD, Pfizer, Novartis, Jaime Branco Speakers bureau: Vitoria, Fernando Pimentel dos Santos Speakers bureau: Novartis, Pfizer, Biogen, Vitoria,


Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 325
Author(s):  
Marco Krasselt ◽  
Christoph Baerwald ◽  
Uwe G. Liebert ◽  
Olga Seifert

Background: The prevalence of herpes zoster (HZ) is high in patients with rheumatic diseases. Systemic lupus erythematosus (SLE) doubles the risk for developing HZ. However, little is known about natural humoral immunity against varicella zoster virus (VZV) in patients with SLE. Hence, we compared VZV IgG antibody concentrations in a group of SLE patients with healthy controls and patients with rheumatoid arthritis (RA). Methods: n = 56 patients with SLE, n = 54 patients with RA, and n = 56 healthy controls were included in this study. The VZV IgG antibody concentration was measured using an enzyme-linked immunosorbent assay (ELISA). The antibody concentrations were compared between the groups. Results: Overall IgG antibody titers for VZV in SLE patients were comparable to healthy controls but higher when compared to patients with rheumatoid arthritis (p = 0.0012). In consequence, antibody levels in controls were higher than in RA patients (p = 0.0097). Stratification by age revealed highest titers among SLE patients in the fourth life decade (p = 0.03 for controls, p = 0.0008 for RA patients) whereas RA patients in their sixth decade had the lowest antibody concentration (p = 0.03 for controls, p = 0.04 for SLE patients). Regarding the individual HZ history, antibody levels of SLE patients with a positive history exceeded all other groups. Conclusions: Although humoral VZV immunity in SLE patients is comparable to healthy controls it seems to be pronounced in young SLE patients between 30 and 39. The lowest VZV IgG levels were found in RA patients. HZ seems to induce antibody production, particularly in patients with SLE. Immunological processes might contribute to VZV antibody levels in SLE patients, but further investigations are needed to substantiate this hypothesis. Even though the increased HZ prevalence seems to be independent of humoral immunity in SLE patients, reduced humoral immunity might contribute to HZ in RA patients. The available HZ subunit vaccination might be an appropriate way to reduce the HZ risk in patients with rheumatic diseases.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1049.3-1050
Author(s):  
E. Gerasimova ◽  
T. Popkova ◽  
T. Kirichenko ◽  
А . Markin ◽  
Y. Markina ◽  
...  

Background:The study of the ability of monocytes to activate associated with the clinical activity of immunological markers of inflammation in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) will provide important and fundamentally new information on the involvement of these cells in the development of autoimmune rheumatic diseases (ARDs).Objectives:To study macrophage activation in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients (pts).Methods:A total of 21 active ARDs pts (11 RA, 10 SLE) were enrolled in the study (median age was 55[44; 63] years; disease duration was 8 [2; 14] months). There are 11 pts with early RA (disease duration was ≤12 months), moderate to high activity (DAS28 was 6.1[4.9;6.7]; SDAI was 25(22;31); ACCP was positive in 73% and RF in 87% cases) and 10 pts with active SLE (SLADAI-2K was 7 [6;8]) in the study. All early RA pts and 4 SLE pts were not treated with glucocorticoids and disease-modifying antirheumatic drugs. Six SLE pts received low-dose glucocorticoids and hydroxychloroquine.All pts were assessed for macrophage activation and laboratory data: ESR, RF, ACCP, CRP, ANA, anti-dsDNA. Isolation of monocytes was carried out according to the standard procedure for obtaining a leukocyte fraction in a Ficoll gradient and subsequent selection of CD14 + cells using magnetic separation. After isolation, the cells were cultured in X-Vivo medium. To assess the degree of monocyte activation, cells were stimulated by the addition of LPS. The value of monocyte activation was expressed as a ratio of the level of secretion of proinflammatory cytokines by monocytes cultured with and without LPS addition. Secretion levels were determined by ELISA. The belonging of the isolated cells to CD14 + monocytes was additionally confirmed by flow cytometry.Results:Macrophage activation was 2.6 (2.0;5.4) and 4.8 (2.8;7.3) in RA and SLE pts, respectively (p>0.05). In RA and SLE pts macrophage activation was independent of age, sex, body mass index, traditional risk factors (arterial hypertension, overweight, smoking, family history of cardiovascular diseases), RA activity scores (DAS28, SDAI), and SLADAI-2K. No association was found between macrophage activation and levels of ESR, RF, ACCP, CRP, ANA, and anti-dsDNA.Conclusion:No differences in macrophage activation were found in RA and SLE pts. Macrophage activation was independent of age, sex, traditional risk factors, and ARD-related parameters. A study on a larger number of pts will clarify the link between macrophage activation and autoimmune disorders.This work was supported by the Russian Science Foundation (Grant № 21-15-00225).Disclosure of Interests:None declared


2021 ◽  
Vol 12 ◽  
Author(s):  
Qi Huang ◽  
Wang-Dong Xu ◽  
Lin-Chong Su ◽  
Xiao-Yan Liu ◽  
An-Fang Huang

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune diseases. CD40 participates in inflammatory response, and promotes fibroblast proliferation, leading to occurrence and progression of SLE, RA. This study explores CD40 gene polymorphisms in SLE and RA patients from a Chinese Han population. Two hundred SLE patients, 340 RA patients, and 900 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood, and six polymorphisms of CD40 gene (rs3765456, rs1569723, rs73115010, rs13040307, rs1883832, and rs4810485) were detected by KASP method. Frequencies of rs1569723 genotypes AA, AC, AA+AC were significantly higher in RA patients as compared to those in healthy controls (P = 0.049, P = 0.024, P = 0.022). Frequencies of genotypes CT, CC+CT of rs1883832, and GT, GG+GT of rs4810485 were significantly higher in RA patients as compared to those in healthy controls (P = 0.012, P = 0.018, P = 0.009, P = 0.015). RA patients carrying rs13040307 C allele and rs73115010 T allele showed increased number of swollen joints. Moreover, frequency of allele T of rs13040307 was lower in SLE patients with positive anti-dsDNA and hematuria as compared to that in patients without these parameters (P = 0.038, P = 0.045). There were increased frequencies of genotype TT, allele T for rs13040307 and lower frequencies of genotype TT, allele T for rs73115010 in lupus patients with myositis (all P&lt;0.05). Interestingly, frequencies of rs1569723 A allele, rs4810485 T allele were higher in SLE patients with myositis, and frequencies of rs3765456 A allele, rs1883832 T allele were lower in SLE patients with myositis (All P&lt;0.05). In conclusion, CD40 gene polymorphisms may associate with susceptibility to SLE and RA.


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