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  • 1
    Online Resource
    Online Resource
    SAGE Publications ; 2022
    In:  Biomarker Insights Vol. 17 ( 2022-01), p. 117727192210917-
    In: Biomarker Insights, SAGE Publications, Vol. 17 ( 2022-01), p. 117727192210917-
    Abstract: Rheumatoid arthritis (RA) is occasionally complicated with interstitial lung disease (ILD). A recent genome-wide association study of ILD in RA reported an association with the polymorphism rs12702634 in RPA3-UMAD1. We conducted an association study of this variant with ILD in Japanese RA patients to replicate this association. Methods: Genotyping of rs12702634 was performed in 175 RA with ILD and 411 RA without chronic lung disease. Results: No association was detected for rs12702634 with ILD in RA ( P = .6369, odds ratio [OR] 1.13, 95% confidence interval [CI] 0.72-1.78). Meta-analysis of these data combined with the data from the recent report showed no significant association ( P = .0996, OR 1.52, 95% CI 0.92–2.49). Conclusions: The present study demonstrated no association of RPA3-UMAD1 rs12702634 with ILD in RA, suggesting the heterogeneity of the disease.
    Type of Medium: Online Resource
    ISSN: 1177-2719 , 1177-2719
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2256754-9
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  • 2
    In: Human Genomics, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2021-01-28)
    Abstract: Autoimmune hepatitis (AIH) is a rare chronic progressive liver disease with autoimmune features. It mainly affects middle-aged women. AIH is occasionally complicated with liver cirrhosis that worsens the prognosis. Genetic and environmental factors are involved in the pathogenesis of AIH. Genetic studies of other diseases have been revealing of pathogenesis and drug efficacy. In this review, we summarize the genetic risk factors for AIH, including human leukocyte antigen ( HLA ) and non- HLA genes. A genome-wide association study (GWAS) on European AIH revealed the strongest associations to be with single nucleotide variants (SNVs) in HLA . Predisposing alleles for AIH were DRB1*03:01 and DRB1*04:01 in Europeans; DRB1*04:04 , DRB1*04:05 , and DRB1*13:01 in Latin Americans; and DRB1*04:01 and DRB1*04:05 in Japanese. Other risk SNVs in non- HLA genes for AIH were found by a candidate gene approach, but several SNVs were confirmed in replication studies. Some genetic factors of AIH overlapped with those of other autoimmune diseases. Larger-scale GWASs of other ethnic groups are required. The results of genetic studies might provide an explanation for the phenotypic heterogeneity of AIH and biomarkers for drug responses.
    Type of Medium: Online Resource
    ISSN: 1479-7364
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2147618-4
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  • 3
    In: Vaccines, MDPI AG, Vol. 10, No. 8 ( 2022-08-21), p. 1365-
    Abstract: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A serological test is used to assess the efficacy of vaccination. It has been reported that anti-SARS-CoV-2 spike (S) and neutralizing antibody (Ab) levels are lower following vaccination in patients with rheumatic disease. Here, we investigated anti-SARS-CoV-2 S and neutralizing Abs in vaccinated rheumatoid arthritis (RA) patients in Japan. Anti-SARS-CoV-2 S and neutralizing Abs were quantified in 101 RA patients and 117 controls. Anti-SARS-CoV-2 S Ab levels were lower in RA patients than both earlier after vaccination in controls (mean RA 324.1 ± 591.8 SDM vs. control 1216.6 ± 854.4 [U/mL], p 〈 0.0001) and later after vaccination (324.1 ± 591.8 vs. 582.0 ± 415.6 [U/mL], p = 0.0002). The interval between vaccination of the RA patients and serum collection was longer than for controls early after vaccination (142.1 ± 31.6 vs. 98.3 ± 11.2 [days] , p 〈 0.0001), but shorter than the later sample from the controls (142.1 ± 31.6 vs. 257.3 ± 11.2 [days], p 〈 0.0001). Importantly, anti-SARS-CoV-2 neutralizing Ab titers in RA patients were higher than in either early or later control samples (10.7 ± 4.9 vs. 8.6 ± 6.6 [%], p = 0.0072, and 10.7 ± 4.9 vs. 3.1 ± 3.7 [%] , p 〈 0.0001, respectively). Anti-SARS-CoV-2 S Ab titers in vaccinated RA patients were lower than in controls, but they were influenced by other clinical manifestations. Anti-SARS-CoV-2 neutralizing Ab levels were independently increased in RA.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2703319-3
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  • 4
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 7 ( 2020-12-17)
    Abstract: Objectives: Interstitial lung disease (ILD) is an extra-articular manifestation in rheumatoid arthritis (RA), detected in 10.7% of patients, and causing a poor prognosis. Hence, biomarkers for ILD are urgently required in RA. Low molecular weight metabolites can be assessed by metabolomic analyses, and although these have been conducted in RA and in idiopathic pulmonary fibrosis, few have been carried out for ILD in the context of RA. Therefore, we analyzed serum metabolomic profiles of ILD in RA to identify novel biomarkers. Methods: Serum samples from 100 RA patients with ILD and 100 matched RA patients without chronic lung disease (CLD) were collected. These samples were subjected to metabolomic analyses using capillary electrophoresis time-of-flight mass spectrometry. Results: A total of 299 metabolites were detected in the metabolomic analysis. By univariate analysis, serum levels of decanoic acid and morpholine were lower in RA with ILD (false discovery rate Q = 1.87 × 10 −11 and 7.09 × 10 −6 , respectively), and glycerol was higher ( Q = 1.20 × 10 −6 ), relative to RA without CLD. Serum levels of these metabolites in RA with usual interstitial pneumonia or RA with non-specific interstitial pneumonia were also altered. The partial least squares-discriminant analysis model generated from these three metabolites could successfully discriminate ILD in RA (area under the curve: 0.919, 95% confidence interval: 0.867–0.968, sensitivity 0.880, specificity 0.780). Conclusions: Serum levels of some metabolites were significantly different in RA with ILD compared with RA without CLD. It is concluded that metabolomic profiling will be useful for discovering candidate screening biomarkers for ILD in RA.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2775999-4
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  • 5
    In: BMC Musculoskeletal Disorders, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-12)
    Abstract: Rheumatoid arthritis (RA) is often complicated with chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway disease, which occur as extra-articular manifestations. CLD in RA have been associated with the production of rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), or anti-carbamylated protein (CarP) antibody. However, few validation studies have been performed thus far. In the present study, we investigated the association of RF, ACPA, and anti-CarP antibodies with RA complicated with CLD. Methods Sera from RA patients with or without CLD were collected. The levels of serum RF, RF immunoglobulin A (IgA), ACPA IgG, ACPA IgA, and ACPA secretory component (SC) were measured using enzyme-linked immunosorbent assay. Results The comparison of RA patients with and without CLD showed that RF IgA was associated with ILD (mean ± standard deviation: 206.6 ± 400.5 vs. 95.0 ± 523.1 U/ml, respectively, P  = 1.13 × 10 − 8 ), particularly usual interstitial pneumonia (UIP) (263.5 ± 502.0 U/ml, P  = 1.00 × 10 − 7 ). ACPA SC was associated with RA complicated with ILD (mean ± standard deviation: 8.6 ± 25.1 vs. 2.3 ± 3.4 U/ml, respectively, P  = 0.0003), particularly nonspecific interstitial pneumonia (NSIP) (10.7 ± 31.5 U/ml, P  = 0.0017). Anti-CarP antibodies were associated with RA complicated with ILD (0.042 ± 0.285 vs. 0.003 ± 0.011 U/ml, respectively, P  = 1.04X10 − 11 ). Conclusion RF IgA and ACPA SC in RA were associated with UIP and NSIP, respectively, suggesting different specificities in patients with RA. Anti-CarP antibodies were associated with ILD in RA. These results may help elucidate the different pathogeneses of UIP and NSIP in RA.
    Type of Medium: Online Resource
    ISSN: 1471-2474
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041355-5
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  • 6
    In: SAGE Open Medicine, SAGE Publications, Vol. 10 ( 2022-01), p. 205031212210880-
    Abstract: The severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019. A serological test is conducted to determine prior infection by severe acute respiratory syndrome coronavirus 2. We investigated whether the results of anti-severe acute respiratory syndrome coronavirus 2 antibody tests are modified in patients with rheumatoid arthritis. Methods: Patients in Japan with rheumatoid arthritis were recruited at Sagamihara Hospital from July 2014 to October 2015 ( n = 38; 2014 cohort) and at Tokyo Hospital from June to October 2020 ( n = 93; 2020 cohort). Anti-severe acute respiratory syndrome coronavirus 2 antibodies were measured by electrochemiluminescence immunoassay or immunochromatographic assay. Results: Anti-severe acute respiratory syndrome coronavirus 2 antibodies were not detected in any of the samples from rheumatoid arthritis patients tested by electrochemiluminescence immunoassay. Anti-severe acute respiratory syndrome coronavirus 2 antibodies were detected by immunochromatographic assay in the 3 (7.9%) serum samples in the 2014 cohort and 15 (16.1%) serum samples in the 2020 cohort. The IgM rheumatoid factor levels were increased in rheumatoid arthritis patients with IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies detected by immunochromatographic assay (mean ± standard deviation (IU/ml), 1223.0 ± 1308.7 versus 503.6 ± 1947.2; P = 0.0101). The levels of IgG rheumatoid factor were also upregulated in rheumatoid arthritis patients with IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies detected by immunochromatographic assay (4.0 ± 0.7 versus 2.4 ± 0.9; P = 0.0013). Conclusion: The results of IgM anti-severe acute respiratory syndrome coronavirus 2 antibody testing by immunochromatographic assay are modified by IgM or IgG rheumatoid factors in rheumatoid arthritis patients.
    Type of Medium: Online Resource
    ISSN: 2050-3121 , 2050-3121
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2735399-0
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  • 7
    Online Resource
    Online Resource
    SAGE Publications ; 2021
    In:  Therapeutic Advances in Musculoskeletal Disease Vol. 13 ( 2021-01), p. 1759720X2110225-
    In: Therapeutic Advances in Musculoskeletal Disease, SAGE Publications, Vol. 13 ( 2021-01), p. 1759720X2110225-
    Abstract: Interstitial lung disease (ILD) is frequently a complication of rheumatoid arthritis (RA) as an extra-articular manifestation which has a poor prognosis. Acute-onset diffuse ILD (AoDILD) occasionally occurs in RA and includes acute exacerbation of ILD, drug-induced ILD, and Pneumocystis pneumonia. AoDILD also confers a poor prognosis in RA. Previously-established biomarkers for ILD include Krebs von den lungen-6 and surfactant protein-D originally defined in patients with idiopathic pulmonary fibrosis; the sensitivity of these markers for RA-associated ILD (RA-ILD) is low. Although many studies on ILD markers have been performed in idiopathic pulmonary fibrosis, only a few validation studies in RA-ILD or AoDILD have been reported. Biomarkers for RA-ILD and AoDILD are thus still required. Recently, genomic, cytokine, antibody, and metabolomic profiles of RA-ILD or AoDILD have been investigated with the aim of improving biomarkers. In this review, we summarize current preliminary data on these potential biomarkers for RA-ILD or AoDILD. The development of biomarkers on RA-ILD has only just begun. When validated, such candidate biomarkers will provide valuable information on pathogenesis, prognosis, and drug responses in RA-ILD in future.
    Type of Medium: Online Resource
    ISSN: 1759-720X , 1759-7218
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2516075-8
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  • 8
    Online Resource
    Online Resource
    SAGE Publications ; 2022
    In:  Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine Vol. 16 ( 2022-01), p. 117954842210754-
    In: Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, SAGE Publications, Vol. 16 ( 2022-01), p. 117954842210754-
    Abstract: Coronavirus Disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Serological testing for anti-SARS-CoV-2 nucleocapsid (N) antibodies (Abs) and anti-SARS-CoV-2 spike (S) Abs is performed to detect prior COVID-19 infection. It is still controversial which antibodies are the most sensitive and specific, and which can be detected earliest after infection. Here, we evaluated the results of serological tests of anti-SARS-CoV-2 N and S Abs in Japan. METHODS Symptomatic COVID-19 patients (n = 84) and control patients with rheumatoid arthritis (n = 93) were recruited at Tokyo National Hospital. Anti-SARS-CoV-2 N and S Abs were measured by commercial electrochemiluminescence immunoassays. RESULTS The fraction of patients positive for anti-SARS-CoV-2 N and S Abs was highest 〉 14 days after symptom onset. The frequency of anti-SARS-CoV-2 S Ab positivity at this time (80.4%) tended to be slightly but not significantly lower than anti-SARS-CoV-2 N Ab positivity (84.8%). Optimized cut-off levels for anti-SARS-CoV-2 N and S Ab positivity were lower than the manufacturer's recommended cut-off levels. Using multiple linear regression analyzes with anti-SARS-CoV-2 N and S Abs, we created an Ab-index with high sensitivity. CONCLUSION To increase the sensitivity of serological diagnostic tests for COVID-19, it is suggested that both anti-SARS-CoV-2 N and S Abs should be measured and cut-off levels decreased.
    Type of Medium: Online Resource
    ISSN: 1179-5484 , 1179-5484
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2583465-4
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  • 9
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 107, No. 5 ( 2022-04-19), p. e1890-e1898
    Abstract: Atypical femoral fractures (AFFs) are very rare atraumatic or mild trauma fractures in the subtrochanteric region or femoral shaft. Some unique genetic variants in Asian populations might confer susceptibility to AFF, since the incidence of AFFs is higher in Asian populations. Objective Because rare variants have been found to be causative in some diseases and the roles of osteomalacia causative genes have not been reported, we investigated rare variants in genes causing abnormal mineralization. Methods Exome sequencing was performed to detect variants in gene coding and boundary regions, and the frequencies of deleterious rare alleles were compared between Japanese patients with AFF (n = 42) and controls of the 4.7KJPN panel of Tohoku Medical Megabank by whole genome sequencing (n = 4773). Results The frequency of the deleterious rare allele of ENPP1 was significantly increased in AFF (P = .0012, corrected P [Pc] = .0155, OR 4.73, 95% CI 2.15-10.40). In multigene panel analysis, the frequencies of deleterious rare alleles of candidate genes were increased in AFF (P = .0025, OR 2.72, 95% CI 1.49-4.93). Principal component analysis of bone metabolism markers identified a subgroup of patients with AFF with higher frequencies of deleterious rare alleles in ENPP1 (P = 4.69 × 10–5, Pc = .0006, OR 8.47, 95% CI 3.76-19.09) and the candidate genes (P = 1.08 × 10–5, OR 5.21, 95% CI 2.76-9.86). Conclusion AFF is associated with genes including ENPP1 that cause abnormal mineralization, suggesting that osteomalacia is an underlying condition predisposing to AFF and that higher incident rates of AFFs in Asian populations might be explained by the genetic risk factors including ENPP1.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
    detail.hit.zdb_id: 2026217-6
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  • 10
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-06-15)
    Abstract: Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disease characterized by the production of anti-U1 ribonucleoprotein antibodies and systemic symptoms similar to those of some other autoimmune diseases. HLA-DRB1 polymorphisms are important genetic risk factors for MCTD, but precise associations of DRB1 genotypes with MCTD have not been reported in Japanese people. Genotyping of HLA-DRB1 and -DQB1 was performed in Japanese MCTD patients (n = 116) and controls (n = 413). Associations of specific allele carriers and genotype frequencies with MCTD were analyzed.The following alleles were found to be associated with predisposition to MCTD: HLA-DRB1*04:01 ( P  = 8.66 × 10 –6 , Pc  = 0.0003, odds ratio [OR] 7.96, 95% confidence interval [CI] 3.13‒20.24) and DRB1*09:01 ( P  = 0.0189, Pc  = 0.5468, OR 1.73, 95% CI 1.12‒2.67). In contrast, the carrier frequency of the DRB1*13:02 allele ( P  = 0.0032, Pc  = 0.0929, OR 0.28, 95% CI 0.11‒0.72) was lower in MCTD patients than in controls. The frequencies of heterozygosity for HLA-DRB1*04:01/*15 ( P  = 1.88 × 10 –7 , OR 81.54, 95% CI 4.74‒1402.63) and DRB1*09:01/*15 ( P  = 0.0061, OR 2.94, 95% CI 1.38‒6.25) were also higher in MCTD patients. Haplotype and logistic regression analyses suggested a predisposing role for HLA-DRB1*04:01, DQB1*03:03, and a protective role for DRB1*13:02. Increased frequencies of HLA-DRB1*04:01/*15 and DRB1*09:01/*15 heterozygous genotypes were found in Japanese MCTD patients.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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