The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC-E2) antimitochondrial antibodies (AMAs). Anti- PDC-E2 antibodies cross-react specifically w...The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC-E2) antimitochondrial antibodies (AMAs). Anti- PDC-E2 antibodies cross-react specifically with mycobacterial hsp65, and we have demonstrated that the motif SxGDL[ILV]- AE shared by PDC- E2212- 226 and hsp’s is a cross-reactive target. Having found that this same motif is present only in β -galactosidase of Lactobacillus delbrueckii (BGAL LACDE), we hypothesized that this homology would also lead to cross-reactivity. The mimics were tested via ELISA for reactivity and competitive cross-reactivity using sera from100 AMA-positive and 23 AMA-negative PBC patients and 190 controls. An Escherichia colt (ECOLI) PDC-E2 mimic that has been pathogenetically linked to PBC but lacks this motif has been also tested. Anti-BGAL266-280 LACDE antibodies were restricted to AMA-positive patients (54 of 95, 57% ) and belonged to immunoglobulin (Ig) G3. Of the 190 controls, 22 (12% ; P < .001) had anti-BGAL266-280 antibodies, mainly of the IgG4 subclass. ECOLI PDC-E2 reactivity was virtually absent. BGAL266- 280/PDC- E2212- 226 reactivity of the IgG3 isotype was found in 52 (52% ) AMA-positive PBC patients but in only 1 of the controls (P < .001). LACDE BGAL266- 280/PDCXE2212- 226 reactivity was due to cross-reactivity as confirmed via competition ELISA.Antibody affinity for BGAL266- 280 was greater than for PDC- E2 mimics. Preincubation of a multireactive serum with BGAL266- 280 reduced the inhibition of enzymatic activity by 40% , while marginal effect (12% ) or no effect (2% ) was observed in human or ECOLIPDC-E2 mimics. In conclusion, IgG3 antibodies to BGAL LACDE cross-react with the major mitochondrial autoepitope and are characteristic of PBC.展开更多
Background and Purpose:The prognostic value of cardiac troponins and natriure tic peptide in acute ischemic stroke is uncertain. We measured cardiac troponin T (cTnT), cardiac troponin I (cTnI), and N-terminal pro-bra...Background and Purpose:The prognostic value of cardiac troponins and natriure tic peptide in acute ischemic stroke is uncertain. We measured cardiac troponin T (cTnT), cardiac troponin I (cTnI), and N-terminal pro-brain natriuretic pept ide (NT-proBNP) at admission in acute ischemic stroke patients without evident myocardial damage. Methods:In 174 consecutive patients with MRI-confirmed isch emic stroke, serial measurements of cTnT, cTnI, and NT-proBNP were performed at 3 different time points in the hyperacute phase (at admission,on days 1 and 2). Relation of laboratory values to risk factors, stroke subtype classification, a nd clinical outcome after 3 months was analyzed. Results:The highest proportion of raised parameters was found at day 2 for cTnI in 8 of 103(7.8%), at day 3 fo r cTnT in 8 of 174 (4.6%), and NT-proBNP in 114 of 174 (65.5%) patients. Prop ortion of patients with good outcome was significantly reduced in the group with highest NT-proBNP quartile. However, using multivariate regression analysis, n o significant relation to morbidity and mortality was found for cTnT, cTnI, or N T-proBNP. Significant impact on the outcome was detected for lesion size, insul ar involvement,sex, age, and stroke severity. Conclusions:NT-proBNP is raised in nearly two thirds of acute stroke patients, whereas elevated cardiac troponin s are found only in a small number of acute ischemic stroke patients. Neither NT -proBNP nor cardiactroponins influence clinical outcome if other risk factors a re considered.展开更多
文摘The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC-E2) antimitochondrial antibodies (AMAs). Anti- PDC-E2 antibodies cross-react specifically with mycobacterial hsp65, and we have demonstrated that the motif SxGDL[ILV]- AE shared by PDC- E2212- 226 and hsp’s is a cross-reactive target. Having found that this same motif is present only in β -galactosidase of Lactobacillus delbrueckii (BGAL LACDE), we hypothesized that this homology would also lead to cross-reactivity. The mimics were tested via ELISA for reactivity and competitive cross-reactivity using sera from100 AMA-positive and 23 AMA-negative PBC patients and 190 controls. An Escherichia colt (ECOLI) PDC-E2 mimic that has been pathogenetically linked to PBC but lacks this motif has been also tested. Anti-BGAL266-280 LACDE antibodies were restricted to AMA-positive patients (54 of 95, 57% ) and belonged to immunoglobulin (Ig) G3. Of the 190 controls, 22 (12% ; P < .001) had anti-BGAL266-280 antibodies, mainly of the IgG4 subclass. ECOLI PDC-E2 reactivity was virtually absent. BGAL266- 280/PDC- E2212- 226 reactivity of the IgG3 isotype was found in 52 (52% ) AMA-positive PBC patients but in only 1 of the controls (P < .001). LACDE BGAL266- 280/PDCXE2212- 226 reactivity was due to cross-reactivity as confirmed via competition ELISA.Antibody affinity for BGAL266- 280 was greater than for PDC- E2 mimics. Preincubation of a multireactive serum with BGAL266- 280 reduced the inhibition of enzymatic activity by 40% , while marginal effect (12% ) or no effect (2% ) was observed in human or ECOLIPDC-E2 mimics. In conclusion, IgG3 antibodies to BGAL LACDE cross-react with the major mitochondrial autoepitope and are characteristic of PBC.
文摘Background and Purpose:The prognostic value of cardiac troponins and natriure tic peptide in acute ischemic stroke is uncertain. We measured cardiac troponin T (cTnT), cardiac troponin I (cTnI), and N-terminal pro-brain natriuretic pept ide (NT-proBNP) at admission in acute ischemic stroke patients without evident myocardial damage. Methods:In 174 consecutive patients with MRI-confirmed isch emic stroke, serial measurements of cTnT, cTnI, and NT-proBNP were performed at 3 different time points in the hyperacute phase (at admission,on days 1 and 2). Relation of laboratory values to risk factors, stroke subtype classification, a nd clinical outcome after 3 months was analyzed. Results:The highest proportion of raised parameters was found at day 2 for cTnI in 8 of 103(7.8%), at day 3 fo r cTnT in 8 of 174 (4.6%), and NT-proBNP in 114 of 174 (65.5%) patients. Prop ortion of patients with good outcome was significantly reduced in the group with highest NT-proBNP quartile. However, using multivariate regression analysis, n o significant relation to morbidity and mortality was found for cTnT, cTnI, or N T-proBNP. Significant impact on the outcome was detected for lesion size, insul ar involvement,sex, age, and stroke severity. Conclusions:NT-proBNP is raised in nearly two thirds of acute stroke patients, whereas elevated cardiac troponin s are found only in a small number of acute ischemic stroke patients. Neither NT -proBNP nor cardiactroponins influence clinical outcome if other risk factors a re considered.
