Exposure to occupational antigens might predispose to IgG4‐related disease

Wenniger, Lucas J. Maillette de Buy; Culver, Emma L.; Beuers, Ulrich

doi:10.1002/hep.26999

Cited by 105 publications

(61 citation statements)

References 6 publications

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“…Th is gender balance was observed in almost every disease condition in which an elevated serum IgG4 was found. Given that IgG4 is the predominant subclass in situations of chronic exposure and tolerance, it is possible that the older male distribution in IgG4-RD is explained by a long-standing history to certain environmental or occupational antigens, to which IgG4-RD patients have an aberrant response ( 22 ). , elevated serum IgG4 ≥1.4 g l −1 , and moderately elevated serum IgG4 ≥2.8 g l −1 .…”

Section: Serum Igg4 In a Prospective Uk Igg4-rd Cohortmentioning

confidence: 99%

Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort

Culver

Sadler

Simpson

et al. 2016

American Journal of Gastroenterology

175

102

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OBJECTIVES:Elevated serum immunoglobulin G4 (IgG4) levels have been associated with autoimmune pancreatitis and IgG4-related disease (IgG4-RD) for over a decade. However, an elevated serum IgG4 is not specifi c for the disease. There have been inconsistent reports of its use in diagnosis, as a marker of disease relapse, and its relationship to organ involvement in retrospective cohorts. The aims of this study were to ascertain conditions that are associated with an elevated serum IgG4 and to investigate the role of IgG4 in diagnosis, relapse, and organ involvement in a prospective cohort of patients with IgG4-RD. METHODS:We evaluated serum IgG4 measurements in the Oxford Immunology Laboratory over 6 years. Patients in whom serum IgG4 was requested to differentiate IgG4-RD from other diseases were recruited into a longitudinal follow-up study to determine fi nal diagnosis. In a prospective cohort of IgG4-RD patients, organ involvement, response to therapy, and disease relapse were determined. RESULTS:Two thousand and sixty-seven samples from 1,510 patients had serum IgG4 measured. Of these, IgG4 was elevated (≥1.4 g l SUPPLEMENTARY MATERIAL is linked to the online version of the paper at

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Section: Serum Igg4 In a Prospective Uk Igg4-rd Cohortmentioning

confidence: 99%

Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort

Culver

Sadler

Simpson

et al. 2016

American Journal of Gastroenterology

175

102

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“…Our findings were meanwhile confirmed by others showing that high numbers of circulating plasmablasts detected by flow cytometry were specific for several organ manifestations of IgG4-RD [14] . Together, these findings shed a new light on the pathogenesis of IAC and IgG4-RD (high percentage of 'blue collar workers' in the Amsterdam and Oxford cohorts exposed to solvents, paints, oil products, or industrial gases [4] ), but also improved our skills in diagnosing IAC [12,13] . Today a highly accurate diagnostic test for IAC and IgG4-RD appears within reach.…”

Section: Novel Biochemical Markersmentioning

confidence: 82%

“…The majority of them are 'blue collar workers' with long-term (>1 year) or lifelong exposures to solvents, various oil products or industrial gases, which may explain the unusual gender and age distribution [4] . They present with obstructive jaundice, weight loss and/or abdominal discomfort [1] .…”

Section: Patient Characteristics In Iac and Igg4-rdmentioning

confidence: 99%

IgG4-Associated Cholangitis - A Mimic of PSC

Beuers¹,

Hubers²,

Doorenspleet

et al. 2015

Dig Dis

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IgG4-associated cholangitis (IAC) is an inflammatory disorder of the biliary tract representing a major manifestation of IgG4-related disease (IgG4-RD) often with elevation of serum IgG4 levels, infiltration of IgG4+ plasma cells in the affected tissue and good response to immunosuppressive treatment. Its first description may go back to 150 years ago. The clinical presentation of IAC is often misleading, mimicking other biliary diseases such as primary sclerosing cholangitis (PSC) or cholangiocarcinoma. The HISORt criteria - histopathological, imaging, and serological features (sIgG4), other organ manifestations of IgG4-RD and response to treatment - are the standard for the diagnosis of IAC. In this overview of a recent lecture, we summarize our original findings on IgG4-RD that (i) dominant IgG4+ B-cell clones identified by advanced next generation sequencing (NGS) are highly specific for IgG4-RD (meanwhile confirmed by others), are a highly accurate diagnostic marker to distinguish IgG4-RD from PSC and biliary/pancreatic malignancies and may be crucial in unravelling the pathophysiology of IgG4-RD; (ii) sIgG4/sIgG1 >0.24 have additional diagnostic value in comparison to sIgG4 in differentiating IAC from PSC; (iii) blood IgG4 mRNA is a highly accurate diagnostic marker comparable to NGS and may become an easily available and affordable diagnostic standard for distinguishing IgG4-RD from PSC and biliary/pancreatic malignancies; and (iv) ‘blue collar work' with long-term exposure to solvents, paints, oil products or industrial gases may be a risk factor for development of IgG4-RD. These findings may contribute to the understanding of the pathophysiology and to the early diagnosis and adequate treatment of IgG4-RD.

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“…Das hochspezifische Auftreten von IgG4-positiven isolierten B-Zell-Rezeptor-Klonen im peripheren Blut der Betroffenen legt aber die Reaktion gegen spezifische Antigene nahe. Neben prädisponierenden genetischen Faktoren [34] wurde unter anderem die -beispielsweise beruflich bedingte -langjährige Exposition gegenüber Lösungsmitteln, Farben, Diesel und anderen Ölprodukten als möglicher Risikofaktor identifiziert [35]. Dies könnte auch das Vorkommen vor allem bei älteren Männern erklären.…”

Section: Pathogeneseunclassified