Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients

Florin, Lisa; Rubben, Kaat; Vanhaecke, Amber; Devreese, Katrien; Keyser, Filip De; Smith, Vanessa; Bonroy, Carolien

doi:10.1515/cclm-2019-0655

Cited by 11 publications

(7 citation statements)

References 23 publications

(53 reference statements)

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“…Our data agree with previous studies, confirming a significant higher prevalence of ACA in PBC-SSc patients compared to subjects with SSc alone. This datum seems to be in accordance with results from a recent study of Florin et al 31 that showed a strong correlation of different PBCspecific antibodies and ACA and not with the limited cutaneous subset. These data suggest a probable crucial role of ACA in autoimmune disease.…”

Section: Discussionsupporting

confidence: 93%

“…At the same time, PBC-specific autoantibodies may be found in SSc patients also in the absence of cholestatic liver enzyme elevations probably preceding PBC development. 31 Another interpretation of these findings is that the link between SSc and PBC relates more strongly with autoimmunity rather with the severity of fibrosis as demonstrated by the association with the limited cutaneous subset and not with the diffuse one. This could give clues to some pathomechanisms involved in SSc-PBC subphenotype.…”

Section: Discussionmentioning

confidence: 99%

“…At the same time, PBC-specific autoantibodies may be found in SSc patients also in the absence of cholestatic liver enzyme elevations probably preceding PBC development. 31…”

Section: Discussionmentioning

confidence: 99%

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Systemic sclerosis and primary biliary cholangitis: Longitudinal data to determine the outcomes

Lepri

Airò

Distler

et al. 2023

Journal of Scleroderma and Related Disorders

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Background: Several studies described the cross-sectional characteristics of systemic sclerosis patients and coexisting primary biliary cholangitis, but longitudinal prognostic data are lacking. Aims: To describe the systemic sclerosis–primary biliary cholangitis phenotype, including baseline characteristics and outcomes. Methods: We performed a multicentre the European Scleroderma Trials and Research Group study of systemic sclerosis patients with primary biliary cholangitis or with primary biliary cholangitis–specific antibodies, matched with systemic sclerosis controls free from hepatobiliary involvement matched for disease duration and cutaneous subset. Data were recorded at baseline and at the last available visit. Results: A total of 261 patients were enrolled (115 primary biliary cholangitis–systemic sclerosis, 161 systemic sclerosis). At baseline, systemic sclerosis–primary biliary cholangitis patients had a higher prevalence of anti-centromere antibodies ( p = 0.0023) and a lower prevalence of complete absence of digital ulcers. The milder vascular involvement was confirmed at follow-up when crucial differences emerged in the percentage of patients experiencing digital ulcers; a significantly higher number of patients who never experienced digital ulcers were observed among primary biliary cholangitis–systemic sclerosis patients ( p = 0.0015). Moreover, a greater incidence of pulmonary arterial hypertension ( p < 0.001) and of conduction blocks ( p = 0.0256) was observed in systemic sclerosis patients without primary biliary cholangitis. Patients with primary biliary cholangitis had higher levels of liver enzymes at baseline than systemic sclerosis patients; a significant decrease in liver enzymes was observed at follow-up. Out of 18 patients with cholangitis, one received a liver transplant at follow-up. Conclusion: Our data show that systemic sclerosis–primary biliary cholangitis exhibit a mild systemic sclerosis and primary biliary cholangitis phenotype with outcomes being in general favourable.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Systemic sclerosis and primary biliary cholangitis: Longitudinal data to determine the outcomes

Lepri

Airò

Distler

et al. 2023

Journal of Scleroderma and Related Disorders

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“…However, ANA are not specific for PBC and are also present in patients with other immunological disorders and infections without elevated liver enzymes levels. [53,54] Although a possible molecular mimicry between the epitopic regions of E. coli and a nuclear protein Sp100 has been proposed on the basis of a strong correlation between the presence of anti-Sp100 antibodies and AMA positivity in women with recurrent UTI, direct evidence is lacking. [4] The mechanism underlying the induction and generation of ANA in PBC is unknown.…”

Section: Discussionmentioning

confidence: 99%

E. coli and the etiology of human PBC: Antimitochondrial antibodies and spreading determinants

et al. 2021

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Background and Aims:The increased frequency of urinary tract infections in patients with primary biliary cholangitis (PBC) and the cross-reactivity between the lipoyl domains (LD) of human pyruvate dehydrogenase complex (hPDC-E2) and Escherichia coli PDC-E2 (ePDC-E2) have long suggested a role of E. coli in causality of PBC. This issue, however, has remained speculative. We hypothesized that by generating specific constructs of human and E. coli PDC-E2, we would be able to assess the specificity of autoantibody responses and define whether exposure to E. coli in susceptible hosts is the basis for the antimitochondrial antibody (AMA) response.Approach and Results: Importantly, the reactivity of hPDC-E2 LD (hPDC-E2LD) affinity-purified antibodies against hPDC-E2LD could only be removed by prior absorption with hPDC-E2LD and not ePDC-E2, suggesting the presence of unique human PDC-E2 epitopes distinct from E. coli PDC-E2. To identify the autoepitope(s) present in hPDC-E2LD, a more detailed study using a variety of PDC-E2 constructs was tested, including the effect of lipoic acid (LA) on ePDC-E2 conformation and AMA recognition. Individual recombinant ePDCE2 LD domains LD1, LD2 and LD3 did not react with either AMA or antibodies to LA (anti-LA), but in contrast, anti-LA was readily reactive against purified recombinant LD1, LD2, and LD3 expressed in tandem (LP); such reactivity increased when LP was precultured with LA. Moreover, when the three LD (LD1, LD2, LD3) domains were expressed in tandem in pET28a or when LD1 was expressed in another plasmid pGEX, they were lipoylated and reactive to PBC sera.

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“…In the literature screened by our group, we selected 10 articles with relevant data support to make statistics and comparisons on the occurrence probability of clinical manifestations of anti-CENP-B positive SSc patients. As shown in Table 3-3, gastrointestinal involvement had the highest incidence of symptoms (46.44%) [35], followed by telangiectasia (45.25%) and Raynaud's phenomenon (44.23%) [36,37]. However, the data of different studies on these two phenomena were quite different, so the reliability was not high.…”

Section: Distribution Of Clinical Manifestations In Anti-cenp-b(+) Ssc Patientsmentioning

confidence: 99%

The Meta-Analysis About The Expression and Prognosis of Anti-Ro-52, Anti-CENP-B and AMA in Sjogren's Syndrome and Systemic Sclerosis

Shao

Qiu

Yang

et al. 2021

Preprint

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Objective This project aims to investigate the diagnostic value of anti-Ro-52, anti-CENP-B, and AMA in Sjogren's syndrome and systemic sclerosis. Methods We constructed the Meta-analysis to evaluate the existing experimental data and obtain the advantages of the three antinuclear antibodies compared with traditional test items using specific data processing methods and evaluated their value in the diagnosis as well as the differential diagnosis of Sjogren's syndrome and systemic sclerosis. During the process of paper collection, we strictly followed the principle of PICOS to screen the literature, trying to include the literature with a large sample size, controversial and influential results which would make the results of this Meta-analysis more valuable. In this study, Revman and Stata software was used for data processing, and the forest map was drawn to analyze the difference in antibody-positive rate, age, and gender distribution, and other factors. At the same time, a funnel plot was used to evaluate the bias of literature results.Results The positive rate of anti-Ro-52 in SS and SSC was higher than that of anti-SSB (P < 0.00001); The positive rate of anti-CENP-B in SSc patients was higher than that in anti-SSB patients (P < 0.00001), but there was no significant difference in SS patients (P = 0.77); The positive rate of AMA in SS and SSc was significantly lower than that in ANA (P < 0.00001), but the expression of AMA increased in SS patients with autoimmune hepatitis. In patients with anti-Ro-52 positive SS and SSc associated with EBV infection, the former had a significantly increased risk of developing malignant lymphoma, while the latter had more severe symptoms of tissue fibrosis. Conclusion The accuracy of anti-Ro-52 in the diagnosis of SS and SSC is higher. The positive rate of anti-CENP-B in the diagnosis of SSc is higher than that of anti-SSB and anti-Scl-70. SS patients with EBV infection are more likely to develop into malignant lymphoma, while SSc patients with EBV infection have increased skin fibrosis and inflammation.

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Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients

Cited by 11 publications

References 23 publications

Systemic sclerosis and primary biliary cholangitis: Longitudinal data to determine the outcomes

Systemic sclerosis and primary biliary cholangitis: Longitudinal data to determine the outcomes

E. coli and the etiology of human PBC: Antimitochondrial antibodies and spreading determinants

The Meta-Analysis About The Expression and Prognosis of Anti-Ro-52, Anti-CENP-B and AMA in Sjogren's Syndrome and Systemic Sclerosis

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