Genome-wide association studies have firmly established that many genomic loci contribute to inflammatory bowel disease, especially in Crohn’s disease. These studies have newly-established the importance of the inter...Genome-wide association studies have firmly established that many genomic loci contribute to inflammatory bowel disease, especially in Crohn’s disease. These studies have newly-established the importance of the interleukin 23 and autophagy pathways in disease pathogenesis. Future challenges include: (1) the establishment of precisely causal alleles, (2) definition of altered functional outcomes of associated and causal alleles and (3) integration of genetic findings with environmental factors.展开更多
AIM:To investigate the correlation between the appearance of skin lesions and concentration of interleukin(IL)-17A,IL-23 and interferon-γ(IFN-γ)in Crohn’s disease(CD)patients during anti-tumor necrosis factor-α(T...AIM:To investigate the correlation between the appearance of skin lesions and concentration of interleukin(IL)-17A,IL-23 and interferon-γ(IFN-γ)in Crohn’s disease(CD)patients during anti-tumor necrosis factor-α(TNF-α)therapy METHODS:A prospective study included 30 adult patients with CD of Caucasian origin(19 men and 11women;mean age±SD 32.0±8.6 years)during biological therapy with anti-TNF-αantibodies from January2012 to March 2013.Eighteen patients were treated with infliximab,seven with adalimumab and five withcertolizumab.Inclusion criteria were exacerbation of the underlying disease,Crohn’s Disease Activity Index over 300 and the ineffectiveness of previously used non-biological therapies.Patients with a history of psoriasis,atopic dermatitis and other autoimmune skin lesions were excluded from the study.The control group consisted of 12 healthy subjects.A diagnostic survey was carried out,blood tests and careful skin examination were performed,and the serum levels of IL-17,IL-23 and IFN-γwere measured using an enzyme-linked immunosorbent assays technique.Dermatoses that have developed in the course of biological therapy in patients who had no pre-existing skin lesions of similar character were qualified as skin lesions induced by antiTNF-αtherapy.RESULTS:Skin manifestations occurred in 18 of CD patients during the anti-TNF-αtherapy(60%),in the average time of 10.16±3.42 mo following the beginning of the 52-wk treatment cycle.Skin lesions observed in CD patients during biological therapy included psoriasiform lesions(44.4%),and eczema forms lesions(22.2%).In CD patients with drug induced skin lesions significantly higher levels of hemoglobin(13.3±1.5 g/dL vs 10.8±1.9 g/dL,P=0.018)and hematocrit(39.9%±4.5%vs 34.3%±5.4%,P=0.01),as well as a significantly lower level of platelets(268±62×103/μL vs 408±239×103/μL,P=0.046)was observed compared with CD patients without skin manifestations.The concentrations of IL-17A and IL-23in CD patients with skin lesions developed under antiTNF-αtherapy were significantly higher compared to those in patients without lesions(IL-17A:39.01±7.03pg/mL vs 25.71±4.90 pg/mL,P=0.00004;IL-23:408.78±94.13 pg/mL vs 312.15±76.24 pg/mL,P=0.00556).CONCLUSION:Skin lesions in CD patients during bio-logical therapy may result from significantly increased concentrations of IL-17A and IL-23,which are strongly associated with TNF-α/Th1 immune pathways.展开更多
AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD gene...AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed <19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced signifi cantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.展开更多
Background:There is a need for effective and safe therapies for psoriasis that provide sustained benefits.The aim of this study was to assess the efficacy and safety of tildrakizumab,an anti-interleukin-23p19 monoclon...Background:There is a need for effective and safe therapies for psoriasis that provide sustained benefits.The aim of this study was to assess the efficacy and safety of tildrakizumab,an anti-interleukin-23p19 monoclonal antibody,for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods:In this multi-center,double-blind,phase III trial,patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned(1:1)to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4.Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12,16,and every 12 weeks thereafter.Patients in the tildrakizumab group continued with tildrakizumab at week 16,and every 12 weeks until week 52.The primary endpoint was the Psoriasis Area and Severity Index(PASI 75)response rate at week 12.Results:At week 12,tildrakizumab demonstrated significantly higher PASI 75 response rates(66.4%[73/110]vs.12.7%[14/110];difference,51.4%[95%confidence interval(CI),40.72,62.13];P<0.001)and Physician’s Global Assessment(60.9%[67/110]vs.10.0%[11/110];difference,49.1%[95%CI,38.64,59.62];P<0.001)compared to placebo.PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups,reaching maximal efficacy after 28 weeks(86.8%[92/106]vs.82.4%[89/108])and maintained up to 52 weeks(91.3%[95/104]vs.87.4%[90/103]).Most treatment-emergent adverse events were mild and not related to tildrakizumab.Conclusion:Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration:ClinicalTrials.gov,NCT05108766.展开更多
文摘Genome-wide association studies have firmly established that many genomic loci contribute to inflammatory bowel disease, especially in Crohn’s disease. These studies have newly-established the importance of the interleukin 23 and autophagy pathways in disease pathogenesis. Future challenges include: (1) the establishment of precisely causal alleles, (2) definition of altered functional outcomes of associated and causal alleles and (3) integration of genetic findings with environmental factors.
基金Supported by The student’s grant from the Foundation for Medical University of Lodz
文摘AIM:To investigate the correlation between the appearance of skin lesions and concentration of interleukin(IL)-17A,IL-23 and interferon-γ(IFN-γ)in Crohn’s disease(CD)patients during anti-tumor necrosis factor-α(TNF-α)therapy METHODS:A prospective study included 30 adult patients with CD of Caucasian origin(19 men and 11women;mean age±SD 32.0±8.6 years)during biological therapy with anti-TNF-αantibodies from January2012 to March 2013.Eighteen patients were treated with infliximab,seven with adalimumab and five withcertolizumab.Inclusion criteria were exacerbation of the underlying disease,Crohn’s Disease Activity Index over 300 and the ineffectiveness of previously used non-biological therapies.Patients with a history of psoriasis,atopic dermatitis and other autoimmune skin lesions were excluded from the study.The control group consisted of 12 healthy subjects.A diagnostic survey was carried out,blood tests and careful skin examination were performed,and the serum levels of IL-17,IL-23 and IFN-γwere measured using an enzyme-linked immunosorbent assays technique.Dermatoses that have developed in the course of biological therapy in patients who had no pre-existing skin lesions of similar character were qualified as skin lesions induced by antiTNF-αtherapy.RESULTS:Skin manifestations occurred in 18 of CD patients during the anti-TNF-αtherapy(60%),in the average time of 10.16±3.42 mo following the beginning of the 52-wk treatment cycle.Skin lesions observed in CD patients during biological therapy included psoriasiform lesions(44.4%),and eczema forms lesions(22.2%).In CD patients with drug induced skin lesions significantly higher levels of hemoglobin(13.3±1.5 g/dL vs 10.8±1.9 g/dL,P=0.018)and hematocrit(39.9%±4.5%vs 34.3%±5.4%,P=0.01),as well as a significantly lower level of platelets(268±62×103/μL vs 408±239×103/μL,P=0.046)was observed compared with CD patients without skin manifestations.The concentrations of IL-17A and IL-23in CD patients with skin lesions developed under antiTNF-αtherapy were significantly higher compared to those in patients without lesions(IL-17A:39.01±7.03pg/mL vs 25.71±4.90 pg/mL,P=0.00004;IL-23:408.78±94.13 pg/mL vs 312.15±76.24 pg/mL,P=0.00556).CONCLUSION:Skin lesions in CD patients during bio-logical therapy may result from significantly increased concentrations of IL-17A and IL-23,which are strongly associated with TNF-α/Th1 immune pathways.
基金The National Minister of Health grant, No. RC0702GA35
文摘AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed <19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced signifi cantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.
文摘Background:There is a need for effective and safe therapies for psoriasis that provide sustained benefits.The aim of this study was to assess the efficacy and safety of tildrakizumab,an anti-interleukin-23p19 monoclonal antibody,for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods:In this multi-center,double-blind,phase III trial,patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned(1:1)to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4.Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12,16,and every 12 weeks thereafter.Patients in the tildrakizumab group continued with tildrakizumab at week 16,and every 12 weeks until week 52.The primary endpoint was the Psoriasis Area and Severity Index(PASI 75)response rate at week 12.Results:At week 12,tildrakizumab demonstrated significantly higher PASI 75 response rates(66.4%[73/110]vs.12.7%[14/110];difference,51.4%[95%confidence interval(CI),40.72,62.13];P<0.001)and Physician’s Global Assessment(60.9%[67/110]vs.10.0%[11/110];difference,49.1%[95%CI,38.64,59.62];P<0.001)compared to placebo.PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups,reaching maximal efficacy after 28 weeks(86.8%[92/106]vs.82.4%[89/108])and maintained up to 52 weeks(91.3%[95/104]vs.87.4%[90/103]).Most treatment-emergent adverse events were mild and not related to tildrakizumab.Conclusion:Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration:ClinicalTrials.gov,NCT05108766.
