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: Antinuclear antibodies (ANA) giving a rim-like/membranous (RL/M) or a multiple nuclear dot (MN- D)pattern are highly specific for primary biliary cirrhosis (PBC).Aim and subj ects: To assess the prevalence...Background: Antinuclear antibodies (ANA) giving a rim-like/membranous (RL/M) or a multiple nuclear dot (MN- D)pattern are highly specific for primary biliary cirrhosis (PBC).Aim and subj ects: To assess the prevalence of PBC specific ANAs, their Ig isotype, and their clinical significance in 90 PBC patients from Greece and Spain. Twenty eight pa tients with chronic hepatitis C, 23 patients with systemic lupus erythematosus,a nd 17 healthy subjects were studied as controls.Methods: PBC specific ANA reacti vity was tested by indirect immunofluorescence using HEp2 cells as substrate and individual Ig class (IgG, IgA, IgM) and IgG subclass (IgG1, IgG2,IgG3, IgG4) sp ecific antisera as revealing reagents. Results:Fourteen of 90 (15.6%) PBC patie nts had PBC specific ANA reactivity when an anti-IgG (total) antiserum was used as the revealing reagent while 58 (64.4%) were positive when specific antisera to each of the four IgG isotypes were used. The prevailing isotype was IgG3 for MND and IgG1 for RL/M. PBC patients with specific ANA, in particular of the IgG 3 isotype,had significantly more severe biochemical and histological disease com pared with those who were seronegative. None of the controls was positive. Concl usions: Disease specific ANA are present in the majority of patients with PBC wh en investigated at the level of immunoglobulin isotype. PBC specific ANA,in part icular of the IgG3 isotype, are associated with a more severe disease course, po ssibly reflecting the peculiar ability of this isotype to engage mediators of da mage.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: Antinuclear antibodies (ANA) giving a rim-like/membranous (RL/M) or a multiple nuclear dot (MN- D)pattern are highly specific for primary biliary cirrhosis (PBC).Aim and subj ects: To assess the prevalence of PBC specific ANAs, their Ig isotype, and their clinical significance in 90 PBC patients from Greece and Spain. Twenty eight pa tients with chronic hepatitis C, 23 patients with systemic lupus erythematosus,a nd 17 healthy subjects were studied as controls.Methods: PBC specific ANA reacti vity was tested by indirect immunofluorescence using HEp2 cells as substrate and individual Ig class (IgG, IgA, IgM) and IgG subclass (IgG1, IgG2,IgG3, IgG4) sp ecific antisera as revealing reagents. Results:Fourteen of 90 (15.6%) PBC patie nts had PBC specific ANA reactivity when an anti-IgG (total) antiserum was used as the revealing reagent while 58 (64.4%) were positive when specific antisera to each of the four IgG isotypes were used. The prevailing isotype was IgG3 for MND and IgG1 for RL/M. PBC patients with specific ANA, in particular of the IgG 3 isotype,had significantly more severe biochemical and histological disease com pared with those who were seronegative. None of the controls was positive. Concl usions: Disease specific ANA are present in the majority of patients with PBC wh en investigated at the level of immunoglobulin isotype. PBC specific ANA,in part icular of the IgG3 isotype, are associated with a more severe disease course, po ssibly reflecting the peculiar ability of this isotype to engage mediators of da mage.
