scholarly journals Diagnostic and Predictive Utility of Serum Interleukin-37 in Rheumatoid Arthritis: A Case-Control Study

2021 ◽  
Vol 1 ◽  
pp. 97-101
Author(s):  
Faiq Gorial ◽  
Samaa Ezat ◽  
Mahmood Raheem Mahmood

Background: Rheumatoid arthritis is the most common cause of inflammatory polyarthritis. Interleukin‐37 (IL-37) has been found to play an important regulatory role in the development of inflammatory diseases. Objectives: To assess serum IL-37 level in rheumatoid arthritis (RA) patients compared to controls, to evaluate its diagnostic and predictive utility in RA patients and to investigate IL-37 level correlation with demographic and clinical characteristics of RA. Methods: Eighty subjects, 40 RA patients aged between 23-63 years and 40 healthy controls aged between 28-67 years were evaluated. An enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum IL-37 levels. Results: Serum IL-37 was significantly higher in RA patients compared to healthy controls. At optimum cut off value of >58.275 pg/ml, serum IL-37 had 100% accuracy, positive predictive value, negative predictive value, sensitivity, and specificity. Serum IL‐37 level was not significantly related to Disease Activity Score of 28 joints‐erythrocyte sedimentation rate (DAS28‐ESR), also not correlated with C-reactive protein(CRP), rheumatoid factor(RF) and anti-cyclic citrullinated peptide antibody (Anti-CCP). Also there was no correlation between the level of IL-37 and treatment. Conclusions: IL-37 was significantly higher in RA patients compared to healthy controls with a high diagnostic and predictive ability, and may be a potential biomarker for diagnosis and prediction of RA.

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Ting Xia ◽  
Xing-feng Zheng ◽  
Bao-hua Qian ◽  
He Fang ◽  
Jun-jie Wang ◽  
...  

Interleukin- (IL-) 37 is a novel anti-inflammatory cytokine that suppresses immune response and inflammation. This study was performed to determine whether IL-37 was elevated in patients with rheumatoid arthritis (RA) and investigate the correlation between IL-37 level and disease activity and the concentration of Th1/Th2/Th17-related cytokines. Clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP), were collected in 34 RA patients and 34 age- and sex-matched healthy controls. Plasma IL-37 was measured by ELISA. Plasma levels of TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, IFN-γ, MCP-1, and MIP-1βwere analyzed using the Bio-Plex suspension array system. It was found that IL-37 levels were elevated markedly in RA patients and almost undetectable in healthy controls. In addition, IL-37 levels in patients with active RA were significantly enhanced as compared with those in patients of remission. More importantly, IL-37 showed a significant correlation with disease activity (DAS28) and IL-4, IL-7, IL-10, IL-12, and IL-13 concentrations in RA patients. These findings suggest that IL-37 plays an important role in the pathogenesis of RA and may prove to be a potential biomarker of active RA.


Author(s):  
Jon Roger Eidet ◽  
Maja Akopian ◽  
Ole K. Olstad ◽  
Øystein Kalsnes Jørstad ◽  
Morten C. Moe ◽  
...  

Abstract Background To identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls. Methods Thirteen patients (40.1 ± 16.2 years of age) with unilateral AAU, seven patients with unilateral bacterial keratitis (40.2 ± 15.3 years of age), and 14 healthy subjects (41.1 ± 11.6 years of age) were included. The tear proteome of affected eyes was compared with that of the unaffected eye or healthy controls. Proteins were identified by liquid chromatography tandem mass spectrometry and enzyme-linked immunosorbent assay. Results Relative protein ratios were detected and calculated for 272 unique proteins. Compared with healthy controls and the unaffected eye, the top upregulated proteins in AAU eyes were submaxillary gland androgen regulated protein 3B (SMR3B) and SMR3A. Similarly, the top upregulated proteins in bacterial keratitis were S100 calcium-binding protein A9 and orosomucoid 2. The acute phase response protein Serpin Family A Member 3 (SERPINA3) was increased in the healthy eye of AAU patients (P = 0.019) compared with healthy controls. Laser flare measurements in affected eyes of AAU patients showed positive logarithmic correlation with SERPINA3 in tear samples of the unaffected eye (P = 0.022). The use of SERPINA3 as a tear biomarker yielded a sensitivity of 85% and a specificity of 71% in detecting patients with AAU in the study population. Conclusions The acute phase response protein SERPINA3 was increased in tear samples of unaffected eyes of patients with unilateral AAU compared with healthy controls. This study highlights SERPINA3 as a potential biomarker for AAU. Future research should explore the dynamic properties of SERPINA3 in the tear fluid of active and quiescent uveitis eyes.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 518.2-518
Author(s):  
E. Galushko ◽  
A. Semashko ◽  
A. Gordeev ◽  
A. Lila

Background:Anemia of inflammation (AI) and iron deficiency anemia (IDA) are the two most prevalent forms of anemia in patients with rheumatoid arthritis (RA). Diagnosis becomes challenging if AI is associated with true ID (AI/ID), as there is still a lack of a gold standard for differentiation between AI and AI/ID. However, as therapies to overcome anemia differ, proper diagnosis and understanding of underlying pathophysiological regulations are necessary.Objectives:The aim of the study was to evaluate the clinical efficiency of hepcidin, a key regulator of iron metabolism, in the diagnosis of IDA, as well as the differential diagnosis of AI/ID and AI in patients with RA.Methods:The study was undertaken 96 patients with RA, 67 of them were diagnosed anemia according to WHO criteria (104,3±21,4 g/l). Anemic patients and anemia-free patients with RA (n=29) were comparable (p>0.05) in age (44.4±14.8 and 49.8±9.3 years), disease duration (73.5±65.4 and 59.8±48.3 months) and DAS28 (6.3±1.6 and 5.9±1.9). All cases were subjected to following tests: complete blood count with peripheral smear, serum C-reactive protein, serum interleukin-6, iron studies, serum soluble transferrin receptor (sTfR), and serum hepcidin. Patients with RA and anemia were divided two groups: 25 patients with IDA and 42 - with AI. The AI cases were subdivided into pure AI and AI with coexistent ID (n=15).Results:The mean serum hepcidin concentration was significantly increased in pure AI patients (123.85±25.8 ng/mL) as compared to those in IDA patients (63.9±22.8 ng/mL, P < 0.05) and anemia-free patients with RA (88.1±39.09 ng/mL). Also, compared to pure AI patients [normal sTfR levels (<3 µg/mL)], the serum hepcidin concentration was reduced significantly in AI patients with ID [high sTfR levels (≥3 µg/mL)] with a mean of 79.0±23.97 ng/mL.Conclusion:Hepcidin measurement can provide a useful tool for differentiating AI from IDA and also help to identify an iron deficiency in AI patients. This might aid in the appropriate selection of therapy for these patients.Disclosure of Interests:None declared


2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Eman A. Baraka ◽  
Mona G. Balata ◽  
Shereen H. Ahmed ◽  
Afaf F. Khamis ◽  
Enas A. Elattar

Abstract Background This study aimed to measure the serum and synovial interleukin (IL)-37 levels in rheumatoid arthritis (RA) patients compared to patients with primary knee osteoarthritis (PKOA) and healthy controls and to detect its relation to RA disease activity. Results This cross-sectional study included 50 RA patients with a mean age of 40.24 ± 8.62 years, 50 patients with PKOA with a mean age of 56.69 ± 4.21, and 40 healthy controls with a mean age of 41.75 ± 7.38 years. The mean serum IL-37 level in the RA patients (382.6 ± 73.97 pg/ml) was statistically significantly (P < 0.001) the highest among the studied groups; however, it showed a non-significant difference between the PKOA patients (70.38 ± 27.49 pg/ml) and the healthy controls (69.97 ± 25.12 pg/ml) (P > 0.94). Both serum and synovial IL-37 levels were significantly positively correlated with disease activity scores (r = 0.92, P< 0.001 and r = 0.85, P < 0.001), tender joint counts (r = 0.83, P < 0.001 and r = 0.82, P < 0.001 ), swollen joint counts (r = 0.72, P < 0.001 and r = 0.60, P < 0.001), visual analog scale (r = 0.82, P < 0.001 and r = 0.82, P < 0.001), erythrocyte sedimentation rate (r = 0.75, P < 0.001 and r = 0.65, P < 0.001), and C-reactive protein (r = 0.93, P < 0.001 and r = 0.79, P < 0.001), respectively. Conclusion Serum and synovial IL-37 were significantly elevated in the RA patients, and they were closely correlated. Being less invasive, the serum IL-37 could be a marker of disease activity and could reflect the effective disease control by drugs. Having an anti-inflammatory effect could not suggest IL-37 as the key player to control inflammation alone, but its combination with other anti-proinflammatory cytokines could be investigated.


2021 ◽  
Author(s):  
Wu Biao ◽  
Yufeng Chen ◽  
Junlong Zhong ◽  
Shuping Zhong ◽  
Bin Wang ◽  
...  

Abstract Background: Rheumatoid arthritis (RA) is a common autoimmune disease that can occur at any age. If treatment is delayed, RA can seriously affect the patients’ quality of life. However, there is no diagnostic criteria for RA and the positive predictive value of the current biomarkers is moderate. Objective: to identify RA-associated susceptibility genes and explore their potential as a novel biomarker for diagnosis and evaluation of the prognosis of RA.Methods: Peripheral blood mononuclear cells (PBMCs) were collected from healthy human donors and RA patients. RNA-seq analyses were performed to identify the differentially expressed genes (DEGs) between RA and control samples. The PBMCs-mRNA in DEGs were further subjected to enrichment analysis. Furthermore, the hub genes and key modules associated with RA were screened by bioinformatics analyses. Then, the expression of hub genes in RA were assessed in mRNA expression profiles. Next, real time-quantitative PCR (RT-qPCR) analyses were performed to further confirm the expression of the hub genes from the PBMCs that collected from 47 patients with RA and 40 healthy controls. Finally, we evaluated the clinical characters for the candidate mRNAs.Results: RNA-seq analyses revealed the expression of 178 mRNAs from PBMCs were disregulated between the healthy controls and the RA patients. Bioinformatics analyses revealed 10 hub mRNAs. The top 3 significant functional modules screened from PPI network functionally were involved in DNA replication origin binding, chemokine activity, etc. After validating the 10 hub mRNAs in GSE93272 dataset and clinical samples, we identified 3 candidate mRNAs, including ASPM, DTL and RRM2. Among which, RRM2 showed great capacity in discriminating between remissive RA and active RA. Significant correlations were observed between DTL and IL-8, TNF-α, between RRM2 and CDAI, DAS-28, tender joints and swollen joints, respectively. The AUC values of ASPM, DTL and RRM2 were 0.654, 0.995 and 0.990, respectively.Conclusion: We successfully identified multiple candidate mRNAs associated with RA. RRM2 showed high diagnosis efficiency with the AUC of 0.990 (sensitivity=100%, specificity=97.5%). And RRM2 severed as an additional biomarker for evaluating disease activity. The findings provided a novel candidate biomarker for diagnosis and evaluation of the prognosis of RA.


2020 ◽  
Author(s):  
Jian-ting Wen ◽  
Jian Liu ◽  
Hui Jiang ◽  
Lei Wan ◽  
Ling Xin ◽  
...  

Abstract Background: The most severe effects of rheumatoid arthritis (RA) are loss of physical function, which may have a significant impact on self-perception of patient (SPP). However, the inherent relationship between SPP and the key proteins is not clear. The aim of this study was to get an insight into SPP of RA in connection with the the apoptosis-related proteins. Methods: We set out to investigate changes of the apoptosis-related proteins expression in the peripheral blood mononuclear cells (PBMCs) of RA. Additionally, we aimed to correlate the apoptosis-related proteins expression profiles with SPP and clinical indexes. To this end, we employed antibody microarrays of the the apoptosis-related proteins in PBMCs from four RA patients and seven healthy controls. We used bioinformatics to screen several the apoptosis-related proteins. To validate key protein candidates, we performed Enzyme linked immunosorbent assay (ELISA) on 30 RA patients and 30 healthy controls. Results: We found the expression of ten the apoptosis-related proteins (caspase3, CD40, SMAC, HSP27, HTRA, IGFBP-1, IGFBP-6, sTNF-R1, sTNF-R2, TRAILR-3) were significantly altered in PBMCs of RA patients. Receiver operating characteristic (ROC) curve analysis suggested that these ten the apoptosis-related proteins are potential biomarkers of RA. Spearman Correlation analysis and Logistic-regression analysis revealed that the 10 selected the apoptosis-related proteins correlated with SPP and clinical indexes. Conclusion: Therefore, we highlight some the apoptosis-related proteins may serve as potential biomarkers in prediction of SPP for RA patients, although the underlying mechanisms need to be further explored.


2020 ◽  
Vol 14 (4) ◽  
pp. 2453-2465
Author(s):  
Ramadan Yahia ◽  
Shereen M. Mohammed ◽  
Manal M. Hassanien ◽  
Shabaan H. Ahmed ◽  
Helal F. Hetta

Rheumatoid arthritis (RA) is a systemic inflammatory disease with chronic nature of joints related to autoimmunity. Vitamin D was found to modulate cell growth, function of immune cells and anti-inflammatory action. The aims of that study were to investigate serum level of vitamin D and some cytokines and to identify the correlation between vitamin D and these cytokines in RA. Totally 40 RA patients without vitamin D supplement were involved in this study. Serum level of vitamin D, interleukin-6 (IL-6), IL-10, IL-35, C-reactive protein (CRP) and tumor necrosis factor α (TNF-α), all of them were measure in all patients by enzyme-linked immunosorbent assay (ELISA). Patients were classified according to Vitamin D levels into two groups; RA patients with Vit. D deficiency (n=25) and RA patients with Vit. D sufficiency (n=15). IL-6 was lower significantly (P = 0.03) in RA patients with Vit. D sufficiency than RA patients with Vit. D deficiency. IL-10 and IL-35 were higher significantly (P = 0.0234, P = 0.0356 respectively) in RA patients with Vit. D sufficiency than RA patients with Vit. D deficiency. Vit. D was significantly positively correlated with both IL-10 (r = 0.4516, P = 0.0034) and IL-35 (r = 0.3424, P = 0.0329) and negatively correlated with IL-6 (r = -0.3188, P = 0.0479). Sufficient serum level of Vit. D is correlated with higher level of anti-inflammatory cytokines (IL-10 and IL-35) and lower level of IL-6. This support the immunomodulatory effect of Vit. D in RA.


Author(s):  
ABDULNASSER M AL-GEBORI ◽  
MOHAMMED HADI MUNSHED ALOSAMI ◽  
NAWAL HAIDER AL-HASHIMI

Objectives: The objectives of the study were to evaluate changes in 25(OH) Vitamin D levels and some biochemical parameters in rheumatoid arthritis (RA) patients compared with healthy controls and assess the correlation of 25-hydroxy Vitamin D, calcium, magnesium, and disease activity. Study the effects of anti-RA drugs on these biochemical parameters and also the role of supplements calcium and 25-OH Vitamin D in RA patients. Methods: This study conducted between 60 patients for RA and 20 healthy controls according to the American College of Rheumatology standards in 2010. In this study, 25-hydroxy Vitamin D was measured using an enzyme-linked immunosorbent assay, and also some biochemical parameters were measured with a spectrophotometer (Humalyzer 2000). Results: Serum 25(OH) Vitamin D, calcium, magnesium, and albumin levels were significantly lower in RA patients compared with healthy controls. Serum alanine aminotransferase aspartate aminotransferase levels were significantly increased in RA patients compared with healthy controls. The correlation was non-significantly among 25-hydroxy Vitamin D and clinical disease activity index (CDAI), while the results showed significantly inverse correlation calcium and magnesium concentrations with CDAI. Conclusion: 25-OH Vitamin D, calcium, albumin, and magnesium deficiency appear to be widespread in patients with RA. Thus, biochemical changes in RA are reflected in the pathogenesis of RA. Furthermore, in these results, there is no relationship between Vitamin D and the disease activity, while there is a relationship between calcium and magnesium with disease activity.


2020 ◽  
Vol 18 ◽  
pp. 205873922094234
Author(s):  
Heng Xue ◽  
Hui Liu ◽  
Liangpu Xu ◽  
Qiaoling Liu ◽  
Bimin Zhuo ◽  
...  

The aim of this study was to investigate the predictive value of peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) with C-reactive protein (CRP) and white blood cell (WBC) count for community-acquired pneumonia (CAP) in infants. A total of 84 hospitalized infants with CAP and 69 healthy infants were included in this study. The clinical manifestations and laboratory assay results of infants were recorded. Serum Pin1 level was estimated by enzyme-linked immunosorbent assay. The median serum Pin1 concentration in infants with CAP was significantly higher than that in controls (1.44 vs. 0.21 ng/mL, P < 0.0001). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) of the combination Pin1, CRP and WBC (Pin1 + CRP + WBC, 0.943) was higher than Pin1, CRP, WBC alone or the combination of Pin1 and CRP ( P < 0.05). The sensitivity of Pin1 + CRP + WBC (94.0%) was higher than that of Pin1, CRP, WBC alone, or any two combined ( P < 0.05). Pin1 + CRP + WBC also had a high negative predictive value (91.4%). Moreover, serum Pin1 alone had a high specificity (97.0%) and excellent positive predictive value (96.6%) for infants with CAP, which were higher than WBC, Pin1 and WBC in combination, CRP and WBC in combination, and Pin1 + CRP + WBC ( P < 0.05). Therefore, serum Pin 1 was highly expressed in infants with CAP and can singly or in combination with CRP and WBC represent promising novel predictors for infants with CAP.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Leon G. D’Cruz ◽  
Kevin G. McEleney ◽  
Chris Cochrane ◽  
Kyle B. C. Tan ◽  
Priyank Shukla ◽  
...  

AbstractRheumatoid arthritis (RA) is characterised by painful, stiff and swollen joints. RA features sporadic ‘flares’ or inflammatory episodes—mostly occurring outside clinics—where symptoms worsen and plasma C-reactive protein (CRP) becomes elevated. Poor control of inflammation results in higher rates of irreversible joint damage, increased disability, and poorer quality of life. Flares need to be accurately identified and managed. A method comparison study was designed to assess agreement between CRP values obtained by dried blood spot (DBS) versus conventional venepuncture sampling. The ability of a weekly DBS sampling and CRP test regime to detect flare outside the clinic was also assessed. Matched venepuncture and finger lancet DBS samples were collected from n = 100 RA patients with active disease at baseline and 6 weeks (NCT02809547). A subset of n = 30 RA patients submitted weekly DBS samples over the study period. Patient demographics, including self-reported flares were recorded. DBS sample CRP measurements were made by enzyme-linked immunosorbent assay, and venepuncture samples by a reference immunoturbometric assay. Data was compared between sample types by Bland–Altman and weighted Deming regression analyses. Flare detection sensitivity and specificity were compared between ‘minimal’ baseline and 6 week sample CRP data and the ‘continuous’ weekly CRP data. Baseline DBS ELISA assay CRP measures yielded a mean positive bias of 2.693 ± 8.640 (95% limits of agreement − 14.24 to 19.63%), when compared to reference assay data. Deming regression revealed good agreement between the DBS ELISA method and reference assay data, with baseline data slope of 0.978 and intercept -0.153. The specificity of ‘continuous’ area under the curve (AUC) CRP data (72.7%) to identify flares, was greater than ‘minimal’ AUC CRP data (54.5%). This study indicates reasonable agreement between DBS and the reference method, especially at low to mid-range CRP values. Importantly, longitudinal CRP measurement in RA patients helps to clearly identify flare and thus could assist in remote monitoring strategies and may facilitate timely therapeutic intervention.Trial registration: The Remote Arthritis Disease Activity MonitoR (RADAR) study was registered on 22/06/2016 at ClinicalTrials.gov Identifier: NCT02809547. https://clinicaltrials.gov/ct2/show/NCT02809547.


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