Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoantibodies against DNA topoisomerase I (anti-topo I) have been reported to be specific to systemic sclerosis (SSc), however, anti-topo I was detected in patients with silicone breast implants, SLE without features of SSc, and rheumatic diseases. We detected anti-topo I positive silicosis patients without any symptoms of autoimmune diseases. The correlation between anti-topo I autoantibody responses and HLA class II has been established. HLA-DRB1*1502; DQB1*0601 has been reported to be the most frequent anti-topo I associated haplotype among Japanese SSc patients. In this study, haplotype HLA-DR15; DQ6 was detected in all 4 anti-topo I positive Asian Japanese SSc patients randomly selected. Furthermore, HLA-DQB1*0402 was identified in 3 of 4 anti-topo I positive silicosis patients. These findings coincide with the results of a previous study, in which all 4 Japanese patients with anti-topo I had the DQB1*04 alleles, whereas no studies among Caucasian-Americans, African-Americans and Choctaw Indians found the involvement of DQB1*04. We investigated common features among various DQB 1 alleles. HLA-DQB I with a distinct characteristic is clearly involved in the anti-topo I response irrespective of ethnic groups, the main disease, or silica exposure. A common positioning of distinct amino acids, (i.e. positions 14, 30, 57 and 77 of the DQbeta1 domain are methionine, tyrosine, aspartic acid and threonine, respectively,) seems to be associated with anti-topo I response. The above-mentioned amino acid sequence is detected in alleles *0301, *0303, *0306, *0401, *0402, *0601 and *0602.
 ...
PMID:Different distribution of HLA class II alleles in anti-topoisomerase I autoantibody responders between silicosis and systemic sclerosis patients, with a common distinct amino acid sequence in the HLA-DQB1 domain. 1177

The objective of this study is to describe the characteristics of patients with Erasmus syndrome (ES) in a large SSc Brazilian cohort. Nine hundred and forty-seven SSc patients attended at the Scleroderma Outpatient Clinic at two academic medical centers in Brazil and classified as SSc according to the ACR/EULAR criteria were retrospectively studied. Information on demographics, clinical, and laboratory features was obtained by chart review. ES patients had their HLA class II characterized by PCR-SSO method as available. Among the 947 SSc patients studied, nine (0.9 %) had ES. These ES patients were predominantly male (78 %) and smokers (68 %) and presented diffuse SSc (67 %). Mean time of occupational exposure to silica was 13.7 years, with mean age at onset of 47 years. Previous history of tuberculosis was referred by 33 % of the ES patients. All the ES patients presented Raynaud's phenomenon, esophageal involvement, and interstitial lung disease (ILD). Antinuclear antibodies were present in all the ES patients, while anti-topoisomerase I was positive in 44 % and no patient had anticentromere antibody. Three different HLA-DQB alleles (0506, 0305, and 0303) were observed. Compared to non-ES cases, patients with ES were associated with male gender (p < 0.001), diffuse SSc (p < 0.05), ILD (p < 0.05), positive anti-topoisomerase I antibodies (p < 0.05), and death (p < 0.05). Multivariate analysis did not confirm that silicosis is an independent risk factor for SSc. To conclude, ES was rare in this large SSc cohort, although associated with a bad prognosis.
 ...
PMID:Systemic sclerosis and silica exposure: a rare association in a large Brazilian cohort. 2675 24