Background: Several studies illustrated that IL-23/Th17 axis could be an important pro-inflammatory pathway in atherosclerosis. As a key element in this inflammatory mechanism, interleukin-23 receptor (IL-23R) may pla...Background: Several studies illustrated that IL-23/Th17 axis could be an important pro-inflammatory pathway in atherosclerosis. As a key element in this inflammatory mechanism, interleukin-23 receptor (IL-23R) may play a critical role in the pathological process of atherosclerosis. Single nucleotide polymorphisms (SNPs) in IL-23R have recently been consistently found to be associated with atherosclerosis diseases. However, its association with acute coronary syndrome (ACS) is still indistinct. Here, we discussed whether genetic polymorphisms in IL-23R (rs11209026 G/A) were associated with susceptibility to ACS. Methods: Among 160 patients with ACS, it includes 80 patients with unstable angina pectoris (UAP), 80 patients with myocardial infarction (MI), and 80 control subjects were selected randomly. The polymorphisms of IL-23R (rs11209026 G/A) were analyzed by the Sanger method. Results: Data showed that percentages of rs11209026 AG genotypes were significantly lower in ACS group (including: UAP and MI) than in controls (odds ratio [OR] = 0.324, 95% confidence interval [CI]: 0.148 - 0.712, p = 0.005;OR = 0.351, 95% CI: 0.135 - 0.910, p = 0.031;OR = 0.303, 95% CI: 0.112 - 0.817, p = 0.018, respectively). Furthermore, there was no correlation between rs11209026 G/A SNP and dyslipidemia-associated ACS. Conclusions: The variant of the rs11209026 polymorphism in IL-23R gene might decrease the risk of ACS, and these data suggest that AG genotype of the rs11209026 G/A polymorphism may act as a protective factor for acute coronary syndrome and subtype of ACS.展开更多
BACKGROUND Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease.Clinicians now have the unique opportunity to provide individualized treatme...BACKGROUND Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease.Clinicians now have the unique opportunity to provide individualized treatment that can achieve and sustain remission in many patients.However,issues of primary non-response(PNR)and secondary loss of response(SLOR)to non-tumour necrosis factor inhibitor(TNFi)therapies remains a common problem.Specific issues include the choice of optimization of therapy,identifying when dose optimization will recapture response,establishing optimal dose for escalation and when to switch therapy.AIM To explores the issues of PNR and SLOR to non-TNFi therapies.METHODS This review explores the current evidence and literature to elucidate management options in cases of PNR/SLOR.It will also explore potential predictors for response following SLOR/PNR to therapies including the role of therapeutic drug monitoring(TDM).RESULTS In the setting of PNR and loss of response to alpha-beta7-integrin inhibitors and interleukin(IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response.For Janus kinase inhibitors dose optimization can be utilized to recapture response with loss of response.CONCLUSION The role of TDM in the setting of advanced non-TNFi therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future.展开更多
Systemic lupus erythematosus（SLE） is a typical autoimmune disease. Lymphotoxin β receptor（LTβR） signaling plays an important role in autoimmune inflammations. LTβR-Ig fusion protein, LTβR blocking agent, has b...Systemic lupus erythematosus（SLE） is a typical autoimmune disease. Lymphotoxin β receptor（LTβR） signaling plays an important role in autoimmune inflammations. LTβR-Ig fusion protein, LTβR blocking agent, has been used to treat SLE, while its mechanism remains to be fully elucidated. In this study, to investigate the expression of LTβR in the T cells of SLE patients and its roles in the pathogenesis of SLE, we isolated the peripheral blood T cells of SLE patients and normal controls to detect expression of LTβR by flow cytometry and RNA assay. T cells were also stimulated with LIGHT, a ligand of LTβR, and then detected for their LTβR expressions and apoptosis by flow cytometry. Also, their expressions of inflammatory factors and receptors were determined by RNA assay. The results showed that LTβR positive cells were 22.75%±6.98% in CD3~＋ cells of SLE patients, while there were almost no LTβR positive cells in CD3~＋ cells of normal persons. Moreover, LTβR expression was remarkably higher in CD3,CD4 and CD8 positive T cells of active SLE patients than non/low active patients（all P〈0.05）, and positively correlated with increased Ig level, decreased complement level and renal damage. Moreover, the stimulation of SLE T cells with LIGHT promoted higher expression of LTβR, IL-23 R and IL-17 A, and apoptosis of T cells. In conclusion,we demonstrated a high expression of LTβR in the T cells of SLE patients which may be associated with pathogenesis of SLE.展开更多
文摘Background: Several studies illustrated that IL-23/Th17 axis could be an important pro-inflammatory pathway in atherosclerosis. As a key element in this inflammatory mechanism, interleukin-23 receptor (IL-23R) may play a critical role in the pathological process of atherosclerosis. Single nucleotide polymorphisms (SNPs) in IL-23R have recently been consistently found to be associated with atherosclerosis diseases. However, its association with acute coronary syndrome (ACS) is still indistinct. Here, we discussed whether genetic polymorphisms in IL-23R (rs11209026 G/A) were associated with susceptibility to ACS. Methods: Among 160 patients with ACS, it includes 80 patients with unstable angina pectoris (UAP), 80 patients with myocardial infarction (MI), and 80 control subjects were selected randomly. The polymorphisms of IL-23R (rs11209026 G/A) were analyzed by the Sanger method. Results: Data showed that percentages of rs11209026 AG genotypes were significantly lower in ACS group (including: UAP and MI) than in controls (odds ratio [OR] = 0.324, 95% confidence interval [CI]: 0.148 - 0.712, p = 0.005;OR = 0.351, 95% CI: 0.135 - 0.910, p = 0.031;OR = 0.303, 95% CI: 0.112 - 0.817, p = 0.018, respectively). Furthermore, there was no correlation between rs11209026 G/A SNP and dyslipidemia-associated ACS. Conclusions: The variant of the rs11209026 polymorphism in IL-23R gene might decrease the risk of ACS, and these data suggest that AG genotype of the rs11209026 G/A polymorphism may act as a protective factor for acute coronary syndrome and subtype of ACS.
文摘BACKGROUND Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease.Clinicians now have the unique opportunity to provide individualized treatment that can achieve and sustain remission in many patients.However,issues of primary non-response(PNR)and secondary loss of response(SLOR)to non-tumour necrosis factor inhibitor(TNFi)therapies remains a common problem.Specific issues include the choice of optimization of therapy,identifying when dose optimization will recapture response,establishing optimal dose for escalation and when to switch therapy.AIM To explores the issues of PNR and SLOR to non-TNFi therapies.METHODS This review explores the current evidence and literature to elucidate management options in cases of PNR/SLOR.It will also explore potential predictors for response following SLOR/PNR to therapies including the role of therapeutic drug monitoring(TDM).RESULTS In the setting of PNR and loss of response to alpha-beta7-integrin inhibitors and interleukin(IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response.For Janus kinase inhibitors dose optimization can be utilized to recapture response with loss of response.CONCLUSION The role of TDM in the setting of advanced non-TNFi therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future.
文摘Systemic lupus erythematosus（SLE） is a typical autoimmune disease. Lymphotoxin β receptor（LTβR） signaling plays an important role in autoimmune inflammations. LTβR-Ig fusion protein, LTβR blocking agent, has been used to treat SLE, while its mechanism remains to be fully elucidated. In this study, to investigate the expression of LTβR in the T cells of SLE patients and its roles in the pathogenesis of SLE, we isolated the peripheral blood T cells of SLE patients and normal controls to detect expression of LTβR by flow cytometry and RNA assay. T cells were also stimulated with LIGHT, a ligand of LTβR, and then detected for their LTβR expressions and apoptosis by flow cytometry. Also, their expressions of inflammatory factors and receptors were determined by RNA assay. The results showed that LTβR positive cells were 22.75%±6.98% in CD3~＋ cells of SLE patients, while there were almost no LTβR positive cells in CD3~＋ cells of normal persons. Moreover, LTβR expression was remarkably higher in CD3,CD4 and CD8 positive T cells of active SLE patients than non/low active patients（all P〈0.05）, and positively correlated with increased Ig level, decreased complement level and renal damage. Moreover, the stimulation of SLE T cells with LIGHT promoted higher expression of LTβR, IL-23 R and IL-17 A, and apoptosis of T cells. In conclusion,we demonstrated a high expression of LTβR in the T cells of SLE patients which may be associated with pathogenesis of SLE.
