AIM： To study the relationship between anti-β2- glycoprotein Ⅰ （aβ2GPⅠ） antibodies and platelet activation state in patients with ulcerative colitis （UC） and its significance. METHODS： Peripheral blood sampl...AIM： To study the relationship between anti-β2- glycoprotein Ⅰ （aβ2GPⅠ） antibodies and platelet activation state in patients with ulcerative colitis （UC） and its significance. METHODS： Peripheral blood samples were collected from 56 UC patients （34 males and 22 females, aged 43.5 years, range 21-66 years）, including 36 at active stage and 20 at remission stage, and 25 sex-and age-matched controls. The level of aβ2GP Ⅰ was measured by ELISA. The platelet activation markers, platelet activation complex- Ⅰ （PAC- Ⅰ ） and P-selectin （CD62P） were detected by flow cytometry. RESULTS： The A value for IgG aβ2GP Ⅰ in the active UC group was 0.61 ± 0.13, significantly higher than that in the remittent UC and control groups （0.50 ± 0.13 and 0.22 ± 0.14, P 〈 0.01）. There was a significant difference between the two groups （P 〈 0.01）. The A value for IgM aβ2GP Ⅰ in the active and remittent UC groups was 0.43 ± 0.13 and 0.38 ± 0.12, significantly higher than that in the control group （0.20 ± 0.12, P 〈 0.01）. However, there was no significant difference between the two groups （P 〉 0.05）. The PAC- Ⅰ positive rate for the active and remittent UC groups was 30.6% ± 7.6% and 19.6% ± 7.8% respectively, significantly higher than that for the control group （6.3% ± 1.7%,P 〈 0.01）. There was a significant difference between the two groups （P 〈 0.01）. The CD62P positive rate for the active and remittent UC groups was 45.0% ± 8.8% and 31.9% ± 7.8% respectively, significantly higher than that for the control group （9.2% ± 2.7%, P 〈 0.01）. There was a significant difference between the two groups （P 〈 0.01）. In the active UC group, the more severe the state of illness was, the higher the A value for IgG aβ2GP Ⅰ was, and the positive rate for PAC-Ⅰ and CD62P was positively correlated with the state of illness （Faβ2GP Ⅰ = 3.679, P 〈 0.05; FPAC-Ⅰ （%） = 5.346, P 〈 0.01; and FCD62P （%） = 5. 418, P 〈 0.01）. Meanwhile, in the same state of illness, the A value for IgG aβ2GP Ⅰ was positively correlated to the positive rates for PAC-Ⅰ and CD62P. CONCLUSION： aβ2GP Ⅰ level, platelet activation state and their relationship of them are closely correlated with the pathogenesis and development of UC.展开更多
Anti-phospholipid antibodies (APA) like anti-cardiolipin antibodies (ACA) and anti-β2glycoprotien (anti-β2GP) are important cause of venous and arterial thrombosis and other occlusive vascular diseases. The prevalen...Anti-phospholipid antibodies (APA) like anti-cardiolipin antibodies (ACA) and anti-β2glycoprotien (anti-β2GP) are important cause of venous and arterial thrombosis and other occlusive vascular diseases. The prevalence of these antibodies in SLE patients at the time of diagnosis is not known in Indian SLE patients. This study was conducted to evaluate the prevalence of ACA and anti-β2GP autoantibodies in SLE patients and to correlate them with disease activity and immune parameters such as C3, C4 and CRP levels. where 85 SLE patients referred from Rheumatology Department, KEM hospital, Mumbai were studied. SLE disease activity was evaluated by SLE Disease Activity Index (SLEDAI) score at the time of evaluation. All patients studied were in an active stage of disease of which 37.6% patients had renal disorders, which were categorized as Lupus Nephritis (LN) and 62.3% patients did not show any renal manifestations (non-LN). ACA and anti-β2GP autoantibodies, to IgG and IgM subclasses were tested by ELISA. C3, C4 and CRP levels were detected by nephelometer. It was observed that 12.9% patients were IgG-ACA and IgM-ACA positive and ACA positivity was noted more among LN group Anti-β2GP autoantibody positivity was 27.1% for IgG and 31.8% for IgM., IgG-anti-β2GP antibodies were slightly higher in non-LN patients, whereas a higher incidence of IgM-anti-β2GP antibodies were detected in LN patients. Hence detection both ACA and anti-β2GP antibodies along with associated immune parameters were helpful to evaluate their possible association with disease severity in SLE patients. A long term follow up of patients having ACA and anti-β2GP antibodies without thrombotic event is also needed to detect their possible thrombotic event in future along with their clinical presentation.展开更多
Atheromatous plaques usually contain antigens of the periodontitis-causing bacteria Streptococcus mutans though molecular mechanism of this incorporation remains unknown. Since vascular adhesion and inflammatory poten...Atheromatous plaques usually contain antigens of the periodontitis-causing bacteria Streptococcus mutans though molecular mechanism of this incorporation remains unknown. Since vascular adhesion and inflammatory potential of Immune Complexes (IC) are known we investigated the naturally occurring plasma antibodies that recognize major antigens from S. mutans. S. mutans-binding plasma proteins (SMBP) prepared by affinity chromatography on a column of heat-killed S. mutans could recognize α- and β-linked glucose in dextran and yeast respectively but not galactose in glycoproteins. SMBP contained only three proteins, each corresponding in electrophoretic mobility to standard plasma IgG, IgA or IgM. The major positively and negatively charged protein antigens (PSMAg and NSMAg) isolated from S. mutans by electrophoresis and ion exchange chromatography respectively were recognized sugar-reversibly by the anti-β-glucan antibody (ABG) and though less avidly, by the dextran-binding immunoglobulin (DIg) in normal plasma. NSMAg addition resulted in near doubling of IC-bound immunoglobulins in immunoglobulin-rich fraction of plasma. IC isolated from above fraction after NSMAg addition had substantially more IgA and IgM content than total plasma immunoglobulins. IC formation by NSMAg was significantly inhibited by ABG- and DIg-specific sugars or by selective withdrawal of ABG or DIg from plasma. ABG and DIg being relatively high titer plasma antibodies IC formation with them suggested a possible route for vascular adhesion and damage by S. mutans and its antigens. Further, high IgA content of these ICs indicated their susceptibility to tissue uptake through cell surface galectin-1 for which IgA is the lone immunoglobulin ligand.展开更多
AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 ...AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.RESULTS: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients.Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes.Changes in antibody status were more remarkable in CD than UC(ACA IgA: 49.9% vs 23.3% and ACA IgG:21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However,presence of different APLAs were not associated with the clinical phenotype or disease course.展开更多
Background: Hypoxia is one of the most frequently encountered stresses in health and disease. Methods: We compared the effects of an anti-β1 periodontal IgG (pIgG) and an authentic β1 adrenergic agonist, xamoterol, ...Background: Hypoxia is one of the most frequently encountered stresses in health and disease. Methods: We compared the effects of an anti-β1 periodontal IgG (pIgG) and an authentic β1 adrenergic agonist, xamoterol, on isolated myocardium from rat atria contractility. We used an ELISA assay to measure the generation of PGE2 in vitro after the addition of either the antibody or the adrenergic agonist. We analyzed the myocardium histopathologically in the presence of both the antibody and/or the adrenergic agonist drug during normoxia, hypoxia and reperfusion conditions. Results: PGE2 generation increased during the hypoxia and was unchanged during reoxygenation period compared with the production of this prostanoid in atria during normoxia condition. A β1 specific adrenoceptor antagonist atenolol and the β1 synthetic peptide abrogated the increment of the prostanoid in the presence of pIgG but only atenolol due to it in the presence of xamoterol. The increment of PGE2 was dependent on the activation of cox-1 and cox-2 isoforms. Moreover, cox-2 was more active and produced more increments in the production of PGE2 in the presence of the pIgG than cox-1 activation. Histopathologically, studies of myocardium specimens during these different periods of the experimental protocol: basal (B), hypoxia (H) and reoxygenation (R), were also performed and showed tissue necrosis and edematization at the myocardium level. Conclusion: The phenomenon studied here supports the notion that PGE2 may be responsible for tissue edematization. PGE2 maybe acts as a beneficial modulator in the myocardium and prevents a major injury of it. The inflammation damage to the heart organ and cardiomyocytes caused by the actions of the antibodies in the course of heart lesions provoked by cardiovascular autoimmune disease, explains some of these results obtained in the present experiments. Further studies will be needed to establish the real role of PGE2 during hypoxia injury of the heart in the course of autoimmune diseases.展开更多
基金The National Natural Science Foundation of China, No. 30572106
文摘AIM： To study the relationship between anti-β2- glycoprotein Ⅰ （aβ2GPⅠ） antibodies and platelet activation state in patients with ulcerative colitis （UC） and its significance. METHODS： Peripheral blood samples were collected from 56 UC patients （34 males and 22 females, aged 43.5 years, range 21-66 years）, including 36 at active stage and 20 at remission stage, and 25 sex-and age-matched controls. The level of aβ2GP Ⅰ was measured by ELISA. The platelet activation markers, platelet activation complex- Ⅰ （PAC- Ⅰ ） and P-selectin （CD62P） were detected by flow cytometry. RESULTS： The A value for IgG aβ2GP Ⅰ in the active UC group was 0.61 ± 0.13, significantly higher than that in the remittent UC and control groups （0.50 ± 0.13 and 0.22 ± 0.14, P 〈 0.01）. There was a significant difference between the two groups （P 〈 0.01）. The A value for IgM aβ2GP Ⅰ in the active and remittent UC groups was 0.43 ± 0.13 and 0.38 ± 0.12, significantly higher than that in the control group （0.20 ± 0.12, P 〈 0.01）. However, there was no significant difference between the two groups （P 〉 0.05）. The PAC- Ⅰ positive rate for the active and remittent UC groups was 30.6% ± 7.6% and 19.6% ± 7.8% respectively, significantly higher than that for the control group （6.3% ± 1.7%,P 〈 0.01）. There was a significant difference between the two groups （P 〈 0.01）. The CD62P positive rate for the active and remittent UC groups was 45.0% ± 8.8% and 31.9% ± 7.8% respectively, significantly higher than that for the control group （9.2% ± 2.7%, P 〈 0.01）. There was a significant difference between the two groups （P 〈 0.01）. In the active UC group, the more severe the state of illness was, the higher the A value for IgG aβ2GP Ⅰ was, and the positive rate for PAC-Ⅰ and CD62P was positively correlated with the state of illness （Faβ2GP Ⅰ = 3.679, P 〈 0.05; FPAC-Ⅰ （%） = 5.346, P 〈 0.01; and FCD62P （%） = 5. 418, P 〈 0.01）. Meanwhile, in the same state of illness, the A value for IgG aβ2GP Ⅰ was positively correlated to the positive rates for PAC-Ⅰ and CD62P. CONCLUSION： aβ2GP Ⅰ level, platelet activation state and their relationship of them are closely correlated with the pathogenesis and development of UC.
文摘Anti-phospholipid antibodies (APA) like anti-cardiolipin antibodies (ACA) and anti-β2glycoprotien (anti-β2GP) are important cause of venous and arterial thrombosis and other occlusive vascular diseases. The prevalence of these antibodies in SLE patients at the time of diagnosis is not known in Indian SLE patients. This study was conducted to evaluate the prevalence of ACA and anti-β2GP autoantibodies in SLE patients and to correlate them with disease activity and immune parameters such as C3, C4 and CRP levels. where 85 SLE patients referred from Rheumatology Department, KEM hospital, Mumbai were studied. SLE disease activity was evaluated by SLE Disease Activity Index (SLEDAI) score at the time of evaluation. All patients studied were in an active stage of disease of which 37.6% patients had renal disorders, which were categorized as Lupus Nephritis (LN) and 62.3% patients did not show any renal manifestations (non-LN). ACA and anti-β2GP autoantibodies, to IgG and IgM subclasses were tested by ELISA. C3, C4 and CRP levels were detected by nephelometer. It was observed that 12.9% patients were IgG-ACA and IgM-ACA positive and ACA positivity was noted more among LN group Anti-β2GP autoantibody positivity was 27.1% for IgG and 31.8% for IgM., IgG-anti-β2GP antibodies were slightly higher in non-LN patients, whereas a higher incidence of IgM-anti-β2GP antibodies were detected in LN patients. Hence detection both ACA and anti-β2GP antibodies along with associated immune parameters were helpful to evaluate their possible association with disease severity in SLE patients. A long term follow up of patients having ACA and anti-β2GP antibodies without thrombotic event is also needed to detect their possible thrombotic event in future along with their clinical presentation.
文摘Atheromatous plaques usually contain antigens of the periodontitis-causing bacteria Streptococcus mutans though molecular mechanism of this incorporation remains unknown. Since vascular adhesion and inflammatory potential of Immune Complexes (IC) are known we investigated the naturally occurring plasma antibodies that recognize major antigens from S. mutans. S. mutans-binding plasma proteins (SMBP) prepared by affinity chromatography on a column of heat-killed S. mutans could recognize α- and β-linked glucose in dextran and yeast respectively but not galactose in glycoproteins. SMBP contained only three proteins, each corresponding in electrophoretic mobility to standard plasma IgG, IgA or IgM. The major positively and negatively charged protein antigens (PSMAg and NSMAg) isolated from S. mutans by electrophoresis and ion exchange chromatography respectively were recognized sugar-reversibly by the anti-β-glucan antibody (ABG) and though less avidly, by the dextran-binding immunoglobulin (DIg) in normal plasma. NSMAg addition resulted in near doubling of IC-bound immunoglobulins in immunoglobulin-rich fraction of plasma. IC isolated from above fraction after NSMAg addition had substantially more IgA and IgM content than total plasma immunoglobulins. IC formation by NSMAg was significantly inhibited by ABG- and DIg-specific sugars or by selective withdrawal of ABG or DIg from plasma. ABG and DIg being relatively high titer plasma antibodies IC formation with them suggested a possible route for vascular adhesion and damage by S. mutans and its antigens. Further, high IgA content of these ICs indicated their susceptibility to tissue uptake through cell surface galectin-1 for which IgA is the lone immunoglobulin ligand.
基金Supported by Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences,Internal Research Grant of University of Debrecen and the IOIBD Research Grant
文摘AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.RESULTS: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients.Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes.Changes in antibody status were more remarkable in CD than UC(ACA IgA: 49.9% vs 23.3% and ACA IgG:21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However,presence of different APLAs were not associated with the clinical phenotype or disease course.
文摘Background: Hypoxia is one of the most frequently encountered stresses in health and disease. Methods: We compared the effects of an anti-β1 periodontal IgG (pIgG) and an authentic β1 adrenergic agonist, xamoterol, on isolated myocardium from rat atria contractility. We used an ELISA assay to measure the generation of PGE2 in vitro after the addition of either the antibody or the adrenergic agonist. We analyzed the myocardium histopathologically in the presence of both the antibody and/or the adrenergic agonist drug during normoxia, hypoxia and reperfusion conditions. Results: PGE2 generation increased during the hypoxia and was unchanged during reoxygenation period compared with the production of this prostanoid in atria during normoxia condition. A β1 specific adrenoceptor antagonist atenolol and the β1 synthetic peptide abrogated the increment of the prostanoid in the presence of pIgG but only atenolol due to it in the presence of xamoterol. The increment of PGE2 was dependent on the activation of cox-1 and cox-2 isoforms. Moreover, cox-2 was more active and produced more increments in the production of PGE2 in the presence of the pIgG than cox-1 activation. Histopathologically, studies of myocardium specimens during these different periods of the experimental protocol: basal (B), hypoxia (H) and reoxygenation (R), were also performed and showed tissue necrosis and edematization at the myocardium level. Conclusion: The phenomenon studied here supports the notion that PGE2 may be responsible for tissue edematization. PGE2 maybe acts as a beneficial modulator in the myocardium and prevents a major injury of it. The inflammation damage to the heart organ and cardiomyocytes caused by the actions of the antibodies in the course of heart lesions provoked by cardiovascular autoimmune disease, explains some of these results obtained in the present experiments. Further studies will be needed to establish the real role of PGE2 during hypoxia injury of the heart in the course of autoimmune diseases.
