PBC: No Longer a Western Disease?

Tanaka, Atsushi

doi:10.1002/cld.903

Cited by 4 publications

(4 citation statements)

References 12 publications

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“…The etiology and immunological and pathological manifestation of PBC is multifactorial and involves both genetics and environmental factors. In light of recent reports of increasing prevalence of PBC in men, [ 55,56 ] westernization of culture along with improvements in hygiene might account for a changed frequency of UTI and slight change in gender bias in PBC. It is of interest to note that the prevalence of recurrent UTI far exceeds the prevalence of PBC.…”

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…3,9 In Japan, the prevalence of PBC was estimated at approximately 34 per 100 000 in 2016, almost tripling since 2004. 10 This is comparable with European countries such as Iceland and Italy, the United States and Canada, 4 and higher than other Asian countries. 11 A Japanese study conducted between 1982 and 2016 reported that in patients diagnosed after 2010, the prevalence of PBC was higher in women (male/female ratio 1:3.8) and the median age at diagnosis was 60.5 years.…”

Section: Introductionmentioning

confidence: 69%

“…However, its prevalence in the Asia–Pacific region is higher than previously thought 3,9 . In Japan, the prevalence of PBC was estimated at approximately 34 per 100 000 in 2016, almost tripling since 2004 10 . This is comparable with European countries such as Iceland and Italy, the United States and Canada, 4 and higher than other Asian countries 11 .…”

Section: Introductionmentioning

confidence: 79%

Japanese subgroup analysis of GLIMMER: A global Phase IIb study of linerixibat for the treatment of cholestatic pruritus in patients with primary biliary cholangitis

Tanaka

Atsukawa

Tsuji

et al. 2023

Hepatology Research

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“…However, in recent years, these have been more equally shared by the East and West, and this might also explain the lower prevalence of PBC in the East, especially in the past, and the recent increase in prevalence of PBC in the East. 15 The epigenetic studies mentioned above might also explain the geographical disparity. It is possible that populations with a high prevalence of PBC not only have more susceptible genes, but also are more prone to the epigenetic process of developing PBC, in which environmental triggers surround these.…”

Section: Geographical Disparity In Pbc Prevalencementioning

confidence: 99%

Geographical Disparity in Primary Biliary Cholangitis Prevalence: A Mini Review

Wibawa¹,

Shalim²

2022

Gene Expr

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Primary biliary cholangitis (PBC) has been shown to occur more often in the West than in the East. The reason for this geographical disparity remains to be determined. Some researchers have considered that this was merely due to the lack of awareness on PBC in the East. Thus, the reported case and epidemiological studies on this disease remains scarce in the East. Other studies have suggested genetic predisposition and environmental factors proven to play important roles in the disease pathogenesis. In addition, these might also cause the disease to be more susceptible in some populations. The findings reported by multiple genome-wide association studies (GWAS) in recent years have not yet identified the specific genes responsible for the development of PBC, with different susceptible genes identified on each study in different regions. The present review describes some factors that might be associated with this geographical disparity.

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PBC: No Longer a Western Disease?

Cited by 4 publications

References 12 publications

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

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

Japanese subgroup analysis of GLIMMER: A global Phase IIb study of linerixibat for the treatment of cholestatic pruritus in patients with primary biliary cholangitis

Geographical Disparity in Primary Biliary Cholangitis Prevalence: A Mini Review

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