scholarly journals Clinical Significance of Serum Levels of ROM (Reactive Oxygen Metabolites) in Patients With Rheumatoid Arthritis Treated With Biologic Agents as a Predictor for the CDAI-, SDAI-, and Boolean-Remission

2021 ◽  
Author(s):  
Arata Nakajima ◽  
Keiichiro Terayama ◽  
Masato Sonobe ◽  
Yorikazu Akatsu ◽  
Junya Saito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Health Assessment ◽  
Multivariate Logistic Regression Analysis ◽  
Reactive Oxygen ◽  
Serum Levels ◽  
Current Treatment ◽  
Biologic Agents ◽  
Reactive Oxygen Metabolites ◽  
Matrix Metalloproteinase 3 ◽  
Oxygen Metabolites

Abstract We previously showed that reactive oxygen metabolites (ROM) serum levels were associated with the DAS28 in patients with rheumatoid arthritis (RA). In this study, we aimed to investigate whether ROM would be predictive of the CDAI-, SDAI- or Boolean-remission. Fifty-one biologic agents (BA)-naïve RA patients were included in this observational study. Associations between ROM, C-reactive protein (CRP), MMP (matrix metalloproteinase)-3, DAS28-ESR, CDAI, SDAI, and health assessment questionnaire (HAQ) at 12 weeks and the DAS28-, CDAI-, SDAI-, and Boolean-remission at 52 weeks were investigated. The DAS28-, CDAI-, SDAI- and Boolean-remission rates at 52 weeks were 66.7, 52.9, 54.9 and 54.9%, respectively. A multivariate logistic regression analysis revealed that ROM and HAQ at 12 weeks were associated with the CDAI-, SDAI- and Boolean-remission at 52 weeks. Receiver operating characteristic (ROC) analyses demonstrated that the cut-off value for CDAI remission was 389.5 U.Carr, and that for SDAI and Boolean remission was 389.5 U.Carr. ROM at 12 weeks of initial treatment with BAs was a predictor for the CDAI-, SDAI-, and Boolean-remission at 52 weeks. Serum levels of ROM may be a useful biomarker in the current treatment strategy aiming at the early remission of RA.

scholarly journals Serum levels of reactive oxygen metabolites at 12 weeks during tocilizumab therapy are predictive of 52 weeks-disease activity score-remission in patients with rheumatoid arthritis

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Arata Nakajima ◽  
Keiichiro Terayama ◽  
Masato Sonobe ◽  
Yasuchika Aoki ◽  
Hiroshi Takahashi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Index ◽  
Multivariate Logistic Regression Analysis ◽  
Reactive Oxygen ◽  
Serum Levels ◽  
Activity Score ◽  
Reactive Oxygen Metabolites ◽  
Oxygen Metabolites

Abstract Background To verify whether serum levels of reactive oxygen metabolites (ROM) are predictive of future clinical remission in patients with rheumatoid arthritis (RA) receiving tocilizumab (TCZ) therapy. Methods A total of 46 patients with RA receiving TCZ therapy were enrolled in this study. Patients were divided into remission and non-remission groups based on disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) or clinical disease activity index (CDAI) at 52 weeks. Associations between serum levels of ROM, C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3) at 4 and 12 weeks and the remission by DAS28-ESR and CDAI at 52 weeks were investigated. Results There were no significant differences in CRP and MMP-3 between DAS- or CDAI-remission and non-remission groups at 12 weeks. However, ROM in DAS-remission group were significantly lower than those in the non-remission group. For ROM, the area under the curve of the receiver operating characteristic curve was 0.735 and the cut-off value that distinguished DAS-remission group from non-remission group was 305.5 U. Carr (sensitivity: 70.0%, specificity: 72.2%). A multivariate logistic regression analysis revealed that ROM at 12 weeks was associated with DAS-remission at 52 weeks (odds ratio: 6.067, 95% confidence interval: 1.305–28.203). Conclusion Serum levels of ROM at 12 weeks during TCZ therapy may be predictive of DAS-remission at 52 weeks in patients with RA.

scholarly journals IgG anti-hinge antibodies against IgG4 F(ab’)2 fragments generated using pepsin are useful diagnostic markers for rheumatoid arthritis: implications of the possible roles of metalloproteinases and IgG subclasses in generating of immunogenic hinge epitopes.

2020 ◽  
Author(s):  
Toshiyuki Ota ◽  
Shun-ichiro Ota ◽  
Ayumi Uchino ◽  
Shuji Nagano
Keyword(s):  
Rheumatoid Arthritis ◽  
Multivariate Logistic Regression Analysis ◽  
High Specificity ◽  
Serum Levels ◽  
Diagnostic Utility ◽  
Cumulative Number ◽  
Matrix Metalloproteinase 3 ◽  
Cutoff Values ◽  
Independent Variable ◽  
Inhibition Studies

Abstract Background. Pepsin agglutinators, discovered over 50 years ago, have been recently referred to as anti-hinge antibodies (AHAs) because of their reaction with the IgG hinge epitope. AHAs have different reactivity for each hinge epitope generated by each protease that cleaves the hinge region at different sites. Moreover, AHAs have different reactivity against different hinge epitopes derived from each IgG subclass even when the same protease is used. Since the expression of matrix metalloproteinase-3 (MMP-3) is enhanced in rheumatoid arthritis (RA), AHA production could also be increased. The purpose of this study was to determine whether the levels of AHAs against IgG hinge epitopes produced by MMP-3 are elevated in RA.Methods. The serum levels of IgG or IgA AHAs against the IgG1/IgG4 F(ab’)2 fragments, generated by either MMP-3 or pepsin, was measured using ELISA in 111 patients with RA and 81 healthy controls (HC). Receiver operating characteristic (ROC) analysis was used for obtaining optimal cutoff values and cutoff values indicating high specificity (>95%) of the AHA. The targeted epitope of a specific AHA was investigated through inhibition ELISA. Results. Seven AHAs were statistically higher in RA patients than HC, except IgG AHA against IgG1 F(ab’)2, which was generated by MMP-3 proteolytic cleavage. The areas under the ROC curve were of 0.66--0.80, although the sensitivities at high specificity were low (5.4--24.3%). The cumulative number of positive AHAs in each individual was statistically higher in RA patients than HC, suggesting the extreme extent of AHA repertoires in RA. Inhibition studies revealed that IgG AHAs against IgG4 F(ab’)2 fragments generated by pepsin cross-reacted with IgG1 F(ab’)2 fragments generated by pepsin. Multivariate logistic regression analysis identified the IgG AHA against IgG4 F(ab’)2 fragments generated by pepsin as an independent variable for RA diagnosis, even in RA patients who were negative for both RF and ACPA (odds ratio 1.18, 95% CI: 1.06−1.32; P=0.003). Additional experiments using non-RA patients finally strengthened the diagnostic utility.Conclusion. In RA patients, we observed diversification and amplification of AHA repertoires and diagnostic utility of the specific AHA against IgG4 F(ab’)2 fragments generated by pepsin but not MMP-3.

scholarly journals IgG anti-hinge antibodies against IgG4 F(ab’)2 fragments generated using pepsin are useful diagnostic markers for rheumatoid arthritis: implications of the possible roles of metalloproteinases and IgG subclasses in generating of immunogenic hinge epitopes.

2020 ◽  
Author(s):  
Toshiyuki Ota ◽  
Shun-ichiro Ota ◽  
Ayumi Uchino ◽  
Shuji Nagano
Keyword(s):  
Rheumatoid Arthritis ◽  
Operating Characteristic ◽  
Multivariate Logistic Regression Analysis ◽  
High Specificity ◽  
Serum Levels ◽  
Cumulative Number ◽  
Matrix Metalloproteinase 3 ◽  
Cutoff Values ◽  
Independent Variable ◽  
Inhibition Studies

Abstract Background Pepsin agglutinators, discovered over 50 years ago, have been recently referred to as anti-hinge antibodies (AHAs) because of their reaction with the IgG hinge epitope. AHAs have different reactivity for each hinge epitope generated by each protease that cleaves the hinge region at different sites. Moreover, AHAs have different reactivity against different hinge epitopes derived from each IgG subclass even when the same protease is used. Since the expression of matrix metalloproteinase-3 (MMP-3) is enhanced in rheumatoid arthritis (RA), AHA production could also be increased. The purpose of this study was to determine whether the levels of AHAs against IgG hinge epitopes produced by MMP-3 are elevated in RA. Methods The serum levels of IgG or IgA AHAs against the IgG1/IgG4 F(ab’) 2 fragments, generated by either MMP-3 or pepsin, was measured using ELISA in 111 patients with RA and 81 healthy controls (HC). Receiver operating characteristic (ROC) analysis was used for obtaining optimal cutoff values and cutoff values indicating high specificity (>95%) of the AHA. The targeted epitope of a specific AHA was investigated through inhibition ELISA. Results Seven AHAs were statistically higher in RA patients than HC, except IgG AHA against IgG1 F(ab’) 2 , which was generated by MMP-3 proteolytic cleavage. The areas under the ROC curve were of 0.66--0.80, although the sensitivities at high specificity were low (5.4--24.3%). The cumulative number of positive AHAs in each individual was statistically higher in RA patients than HC, suggesting the extreme extent of AHA repertoires in RA. Inhibition studies revealed that IgG AHAs against IgG4 F(ab’) 2 fragments generated by pepsin cross-reacted with IgG1 F(ab’) 2 fragments generated by pepsin. Although the development of IgA AHAs in RA seems to be remarkable and specific, multivariate logistic regression analysis identified the IgG AHA against IgG4 F(ab’) 2 fragments generated by pepsin as an independent variable for RA diagnosis, even in RA patients who were negative for both RF and ACPA (odds ratio 1.18, 95% CI: 1.06−1.32; P =0.003).Conclusion In RA patients, we observed diversification and amplification of AHA repertoires and diagnostic utility of the specific AHA against IgG4 F(ab’) 2 fragments generated by pepsin but not MMP-3.

scholarly journals IgG anti-hinge antibodies against IgG4 F(ab’)2 fragments generated using pepsin are useful diagnostic markers for rheumatoid arthritis: implications of the possible roles of metalloproteinases and IgG subclasses in generating of immunogenic hinge epitopes.

2020 ◽  
Author(s):  
Toshiyuki Ota ◽  
Shun-ichiro Ota ◽  
Ayumi Uchino ◽  
Shuji Nagano
Keyword(s):  
Rheumatoid Arthritis ◽  
Multivariate Logistic Regression Analysis ◽  
High Specificity ◽  
Serum Levels ◽  
Diagnostic Utility ◽  
Cumulative Number ◽  
Matrix Metalloproteinase 3 ◽  
Cutoff Values ◽  
Independent Variable ◽  
Inhibition Studies

Abstract Background. Pepsin agglutinators, discovered over 50 years ago, have been recently referred to as anti-hinge antibodies (AHAs) because of their reaction with the IgG hinge epitope. AHAs have different reactivity for each hinge epitope generated by each protease that cleaves the hinge region at different sites. Moreover, AHAs have different reactivity against different hinge epitopes derived from each IgG subclass even when the same protease is used. Since the expression of matrix metalloproteinase-3 (MMP-3) is enhanced in rheumatoid arthritis (RA), AHA production could also be increased. The purpose of this study was to determine whether the levels of AHAs against IgG hinge epitopes produced by MMP-3 are elevated in RA.Methods. The serum levels of IgG or IgA AHAs against the IgG1/IgG4 F(ab’)2 fragments, generated by either MMP-3 or pepsin, was measured using ELISA in 111 patients with RA and 81 healthy controls (HC). Receiver operating characteristic (ROC) analysis was used for obtaining optimal cutoff values and cutoff values indicating high specificity (>95%) of the AHA. The targeted epitope of a specific AHA was investigated through inhibition ELISA. Results. Seven AHAs were statistically higher in RA patients than HC, except IgG AHA against IgG1 F(ab’)2, which was generated by MMP-3 proteolytic cleavage. The areas under the ROC curve were of 0.66--0.80, although the sensitivities at high specificity were low (5.4--24.3%). The cumulative number of positive AHAs in each individual was statistically higher in RA patients than HC, suggesting the extreme extent of AHA repertoires in RA. Inhibition studies revealed that IgG AHAs against IgG4 F(ab’)2 fragments generated by pepsin cross-reacted with IgG1 F(ab’)2 fragments generated by pepsin. Multivariate logistic regression analysis identified the IgG AHA against IgG4 F(ab’)2 fragments generated by pepsin as an independent variable for RA diagnosis, even in RA patients who were negative for both RF and ACPA (odds ratio 1.18, 95% CI: 1.06−1.32; P=0.003). Additional experiments using non-RA patients finally strengthened the diagnostic utility.Conclusion. In RA patients, we observed diversification and amplification of AHA repertoires and diagnostic utility of the specific AHA against IgG4 F(ab’)2 fragments generated by pepsin but not MMP-3.

scholarly journals Effects of Non-Surgical Periodontal Treatment on Reactive Oxygen Metabolites and Glycemic Control in Diabetic Patients with Chronic Periodontitis

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1056
Author(s):  
Simone Marconcini ◽  
Enrica Giammarinaro ◽  
Saverio Cosola ◽  
Giacomo Oldoini ◽  
Annamaria Genovesi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Glycemic Control ◽  
Systemic Inflammation ◽  
Glycated Hemoglobin ◽  
Reactive Oxygen ◽  
Periodontal Treatment ◽  
Diabetic Patients ◽  
Reactive Oxygen Metabolites ◽  
Periodontal Infection ◽  
Oxygen Metabolites

Background: Periodontal infection may contribute to poor glycemic control and systemic inflammation in diabetic patients. The aim of the present study is to evaluate the efficacy of non-surgical periodontal treatment in diabetic patients by measuring oxidative stress outcomes. Methods: Sixty diabetic patients with periodontitis were enrolled, treated with scaling and full-mouth disinfection, and randomly prescribed chlorhexidine mouthwash, antioxidant mouthwash, or ozone therapy. Reactive oxygen metabolites (ROMs), periodontal parameters, and glycated hemoglobin were measured at baseline and then at 1, 3, and 6 months after. Results: At baseline, all patients presented with pathologic levels of plasmatic ROM (388 ± 21.36 U CARR), higher than the normal population. Probing depth, plaque index, and bleeding on probing values showed significant clinical improvements after treatment, accompanied by significant reductions of plasma ROM levels (p < 0.05). At the 6-month evaluation, the mean ROM relapsed to 332 ± 31.76 U CARR. Glycated hemoglobin decreased significantly (∆ = −0.52 units) after treatment. Both the test groups showed longer-lasting improvements of periodontal parameters. Conclusion: In diabetic patients, periodontal treatment was effective at reducing plasma ROM, which is an indicator of systemic oxidative stress and inflammation. The treatment of periodontal infection might facilitate glycemic control and decrease systemic inflammation.

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