Dataset Information

Risk of sarcoidosis and seropositive rheumatoid arthritis from occupational silica exposure in Swedish iron foundries: a retrospective cohort study.

ABSTRACT: To study the impact of occupational silica exposure on the incidence rates of sarcoidosis and rheumatoid arthritis (RA) in a cohort of exposed workers in Swedish iron foundries.The prevalence of sarcoidosis and RA in a cohort of silica exposed workers was compared with the prevalence in the general Swedish population in this register study. A mixed model was used to calculate silica exposure, and individual silica exposures were used to compute dose responses.Personnel records from 10 iron foundries were used to identify workers whose employment began before 2005 which was then linked to the national non-primary outpatient visits register.The final cohort consisted of 2187 silica-exposed male workers who had been employed for at least 1?year and were still alive without having emigrated when the follow-up study began. The cohort's employment period covers 23 807 person-years at risk.The presented results indicate that moderate to high levels of silica exposure increase risks for sarcoidosis and seropositive RA.Mean levels of airborne silica dust in the foundries decreased significantly between the 1970s and 2000s. Incidence rates of sarcoidosis (3.94; 95%?CI 1.07 to 10.08) and seropositive RA (2.59; 95%?CI 1.24 to 4.76) were significantly higher among highly exposed individuals.Our results reveal increased risks for sarcoidosis and seropositive RA among individuals with high exposure to silica dust (>0.048?mg/m3) compared with non-exposed and less-exposed groups.

SUBMITTER: Vihlborg P

PROVIDER: S-EPMC5642773 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Risk of sarcoidosis and seropositive rheumatoid arthritis from occupational silica exposure in Swedish iron foundries: a retrospective cohort study.

Vihlborg Per P Bryngelsson Ing-Liss IL Andersson Lena L Graff Pål P

BMJ open 20170720 7

<h4>Objective</h4>To study the impact of occupational silica exposure on the incidence rates of sarcoidosis and rheumatoid arthritis (RA) in a cohort of exposed workers in Swedish iron foundries.<h4>Design</h4>The prevalence of sarcoidosis and RA in a cohort of silica exposed workers was compared with the prevalence in the general Swedish population in this register study. A mixed model was used to calculate silica exposure, and individual silica exposures were used to compute dose responses.<h4 ...[more]

PMID: 28729325

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Project description:OBJECTIVE:The pathogenetic mechanisms by which HLA-DRB1 alleles are associated with anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) are incompletely understood. RA high-risk HLA-DRB1 alleles are known to share a common motif, the 'shared susceptibility epitope (SE)'. Here, the electropositive P4 pocket of HLA-DRB1 accommodates self-peptide residues containing citrulline but not arginine. HLA-DRB1 His/Phe13? stratifies with ACPA-positive RA, while His13?Ser polymorphisms stratify with ACPA-negative RA and RA protection. Indigenous North American (INA) populations have high risk of early-onset ACPA-positive RA, whereby HLA-DRB1*04:04 and HLA-DRB1*14:02 are implicated as risk factors for RA in INA. However, HLA-DRB1*14:02 has a His13?Ser polymorphism. Therefore, we aimed to verify this association and determine its molecular mechanism. METHODS:HLA genotype was compared in 344 INA patients with RA and 352 controls. Structures of HLA-DRB1*1402-class II loaded with vimentin-64Arg59-71, vimentin-64Cit59-71 and fibrinogen ?-74Cit69-81 were solved using X-ray crystallography. Vimentin-64Cit59-71-specific and vimentin59-71-specific CD4+ T cells were characterised by flow cytometry using peptide-histocompatibility leukocyte antigen (pHLA) tetramers. After sorting of antigen-specific T cells, TCR? and ?-chains were analysed using multiplex, nested PCR and sequencing. RESULTS:ACPA+ RA in INA was independently associated with HLA-DRB1*14:02. Consequent to the His13?Ser polymorphism and altered P4 pocket of HLA-DRB1*14:02, both citrulline and arginine were accommodated in opposite orientations. Oligoclonal autoreactive CD4+ effector T cells reactive with both citrulline and arginine forms of vimentin59-71 were observed in patients with HLA-DRB1*14:02+ RA and at-risk ACPA- first-degree relatives. HLA-DRB1*14:02-vimentin59-71-specific and HLA-DRB1*14:02-vimentin-64Cit59-71-specific CD4+ memory T cells were phenotypically distinct populations. CONCLUSION:HLA-DRB1*14:02 broadens the capacity for citrullinated and native self-peptide presentation and T cell expansion, increasing risk of ACPA+ RA.

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Dataset Information

Risk of sarcoidosis and seropositive rheumatoid arthritis from occupational silica exposure in Swedish iron foundries: a retrospective cohort study.

Publications

Risk of sarcoidosis and seropositive rheumatoid arthritis from occupational silica exposure in Swedish iron foundries: a retrospective cohort study.

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