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  • BMJ  (87)
  • 1
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 4, No. S1 ( 2016-11)
    Type of Medium: Online Resource
    ISSN: 2051-1426
    Language: English
    Publisher: BMJ
    Publication Date: 2016
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  • 2
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 127.1-127
    Abstract: The main outcomes in SLE patients management are represented by the remission achievement and chronic damage prevention. Even though activity and damage are intimately connected, to date indices including both these outcomes are not available. Objectives: In the present study, we aimed at assessing the application of a new index, the Lupus comprehensive disease control ( LupusCDC ), including disease activity and chronic damage progression. Methods: We performed a longitudinal analysis, including SLE patients according to ACR 1997 criteria, followed-up in the period between January 2014 and December 2018, and with at least one visit per year. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and three different remission levels were evaluated, as reported in Table 1 (1). Table 1. Remission levels considered in the study (1). Remission level Definition Complete Remission ( CR ) No clinical and serological activity (SLEDAI-2K=0) in corticosteroid-free and immunosuppressant-free patients (antimalarials allowed) Clinical remission off-corticosteroids ( ClR-GCoff ) Serological activity with clinical quiescent disease according to SLEDAI-2K in corticosteroid-free patients (stable immunosuppressive therapy and antimalarials allowed) clinical remission on-corticosteroids ( ClR-GCon ) Clinical quiescent disease according to SLEDAI-2K in patients on prednisone 1–5 mg/day (stable immunosuppressants and antimalarials allowed) Chronic damage was registered according to SLICC damage index (SDI). All the patients were evaluated at baseline (T0) and every 12 months (T1, T2, T3, T4). At each time-point, we calculated the prevalence of LupusCDC, defined as remission achievement plus absence of chronic damage progression in the previous one year. We calculated this outcome including separately the different remission levels. Results: According with inclusion criteria, 172 SLE patients were evaluated in the present analysis [M/F 16/156, median age 49 years (IQR 16.7), median disease duration 180 months (IQR 156)]. At first assessment, we observed a mean±SD SDI value of 0.7±1.1. In details, 56 patients (32.5%) showed damage in at least one organ/system and the presence of damage was significantly associated with age (p 〈 0.0001, r=0.3) and disease duration (p=0.0003, r=0.3). During the follow-up, we observed a significant increase in SDI values compared with T0 (T1: mean±DS 0.8±1.3, p 〈 0.0001; T2: 0.8±1.4, p 〈 0.0001; T3: 0.9±1.4 p=0.0001; T4: 1.0±1.5 p 〈 0.0001). In figure 1A and 1B we reported the proportion of patients achieving the different levels of remission and LupusCDC, respectively. In particular, the LupusCDC definition including CR was the most frequently detected in all time-points evaluated (T1: 18.0%; T2: 31.9%; T3: 27.9%; T4: 24.4%), with a significant difference at T2 [LupusCDC(CR) versus LupusCDC(ClR-GCoff), p=0.0002; LupusCDC(CR) versus LupusCDC(ClR-GCon) p=0.0002)], T3 [LupusCDC(CR) versus LupusCDC(ClR-GCoff), p=0.03; LupusCDC(CR) versus LupusCDC(ClR-GCon) p=0.006], T4 [LupusCDC(CR) versus LupusCDC(ClR-GCon), p=0.002]. No significant differences were found when comparing the prevalence of different remission levels and the prevalence of LupusCDC including the corresponding remission. Conclusion: In the present analysis we proposed for the first time a new index including disease activity and chronic damage, in order to evaluate the proportion of SLE patients reaching a comprehensive disease control. We found that CR is most frequently associated with the absence of damage progression. References: [1]Zen M et al. Ann Rheum Dis 2017. Disclosure of Interests: Fulvia Ceccarelli: None declared, Giulio Olivieri: None declared, Lorenzo Dominici: None declared, Alessandra Ida Celia: None declared, enrica cipriano: None declared, Cristina Garufi: None declared, Silvia Mancuso: None declared, Francesco Natalucci: None declared, Valeria Orefice: None declared, Carlo Perricone: None declared, Carmelo Pirone: None declared, viviana antonella pacucci: None declared, Francesca Morello: None declared, Simona Truglia: None declared, Francesca Miranda: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2020
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  • 3
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 75, No. Suppl 2 ( 2016-06), p. 898.1-898
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2016
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  • 4
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 74, No. Suppl 2 ( 2015-06), p. 803.1-803
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2015
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  • 5
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. Suppl 1 ( 2021-06), p. 1073.1-1073
    Abstract: Joint involvement represents one of the most frequent features in patients affected by Systemic Lupus Erythematosus (SLE). This manifestation is characterized by a great heterogeneity in phenotype and severity: the application of more sensitive imaging techniques identified an erosive damage in about 25% of patients (1). This damage has been associated with autoantibodies, such as anti-citrullinated (ACPA) and anti-carbamylated proteins (antiCarP), previously identified in patients Rheumatoid Arthritis (RA) patients. Recently, homocysteinylated alpha 1 antitrypsin (Hcy-1A1AT) has been identified as a new antigenic target of autoantibodies in seronegative RA patients: in detail, anti-homocysteinylated alpha 1 antitrypsin (anti – HATA) antibodies have been identified in 75.7% of patients (2). Objectives: In the present study, we aimed at determining the prevalence of anti – HATA in a cohort of SLE patients. Methods: We evaluated patients affected by SLE according to the 1997 ACR criteria. Demographic, clinical, and laboratory data were collected in a standardized computerized electronically filled form. Each subject underwent peripheral blood sample collection. Hcy-A1AT was obtained by in vitro modification of native A1AT and used as antigens by ELISA to test the presence of anti–HATA in sera obtained from enrolled subjects. Finally, we investigated the presence of ACPA and Rheumatoid Factor (RF) commercial ELISA kits and of anti-CarP (home-made ELISA) by a home-made ELISA in SLE patients’ sera. As control, we enrolled 40 patients affected by Osteoarthritis (OA) and 41 healthy subjects (HS). Results: The present analysis included 88 SLE patients (M/F 6/82 median age 47 years (IQR 17), median disease duration 156 months (IQR 180). Joint involvement was observed in 75 SLE patients (85.2%): in detail, 65 patients referred arthritis and the remaining 10 inflammatory arthralgias. We identified the presence of anti–HATA IgG in 38 SLE patients (43.2%). This prevalence was significantly higher in comparison with OA and HS subjects [15.0% (p 〈 0.001) and 0% (p 〈 0.0001), respectively; Figure 1A]. Focusing on the SLE cohort, no differences were observed between patients with and without joint involvement in anti–HATA IgG prevalence (41.3% versus 34.7%, respectively; p=0.34). However considering SLE patients according to the presence of arthralgia and arthritis, the prevalence of anti-HATA was significantly higher in patients with arthritis in comparison with those patients with arthralgias (46.1% versus 11.1%, p=0.02; figure 1B). Finally, no significant association between anti-HATA and the other tested autoantibodies (RF, ACPA, anti-CarP) was found. Conclusion: We evaluated the prevalence of anti-HATA in a cohort of SLE patients. The prevalence of these autoantibodies was significantly higher in SLE patients than in OA patients and in HS. The association with arthritis suggests a possible role for anti-HATA as biomarkers of SLE-related joint involvement. References: [1]Ceccarelli F. Perricone C. Cipriano E. et al. Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment. Seminar in Arthritis and Rheumatism, 47(1), 53 – 64. [2]Colasanti T. Sabatinelli D. Mancone et al. Homocysteinylated alpha 1 antitrypsin as an antigenic target of autoantibodies in seronegative rheumatoid arthritis patients. Journal of Autoimmunity 2020 Sep;113:102470. Disclosure of Interests: None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2021
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  • 6
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. Suppl 1 ( 2022-06), p. 1354.3-1355
    Abstract: Genetic contribution to development of chronic damage have been scarcely investigated in systemic lupus erythematosus (SLE). In fact, whereas most studies have looked for an association between genetic variants and SLE susceptibility or disease phenotypes, only few have focused on the relationship between these biomarkers and damage development. Objectives Moving from these premises, we firstly analyzed the distribution of organ damage in a cohort of SLE patients and secondly we evaluate the role of clinical and genetic factors in determining the development of chronic damage. Methods Caucasian SLE patients, diagnosed according with 1997 ACR criteria, were enrolled, and clinical and laboratory data were collected. Based on literature data, we selected a panel of 17 SNPs of following genes STAT4, IL10, IRAK1, HCP5, MIR146a, ATG16L1, IRGM, ATG5, MIR124, MIR1279, TNFSF4, CD40. Genotyping was performed by allelic discrimination assays. A phenotype-genotype correlation analysis was performed by evaluating specific domains of SLICC Damage Index (SDI). Results Among 175 Caucasian SLE patients, 105 (60%) exhibited damage (SDI ≥1) with a median value of 1.0 (IQR 3.0). The musculoskeletal (26.2%), neuropsychiatric (24.6%) and ocular domains (20.6%) were involved most frequently. The presence of damage was associated with higher age, longer disease duration, neuropsychiatric (NP) manifestations, anti-phospholipid syndrome and the positivity of anti-dsDNA antibodies. Concerning therapies cyclophosphamide, mycophenolate mofetil and glucocorticoids resulted associated with the development of damage. The genotype/phenotype correlation analysis showed an association between renal damage, identified in 6.9% of patients, and rs2205960 of TNFSF4 (p=0.001; OR 17.0). This SNP resulted significantly associated with end-stage renal disease (p= 0.018, OR 9.68) and estimated GFR 〈 50% (p=0.025, OR 1.06, Figure 1). The rs1463335 of MIR1279 gene was associated with the development of NP damage (p=0.029; OR 2.783). The multivariate logistic regression analysis confirmed the associations between TNFSF4 rs2205960 SNP and renal damage (p=0.020, r=2.53) and between NP damage and rs1463335 of MIR1279 gene (p=0.013, r=1.26)]. Figure 1. Association between renal damage and rs2205960 of TNFSF4 (p=0.001). In addition, this SNP resulted significantly associated with the development of two specific items of SDI renal domain: estimated glomerular filtration rate (GFR) 〈 50% and end-stage renal disease (ESRD) (p=0.025, p=0.018 respectively). Conclusion We showed the role of age, drugs, and autoantibody profile in determining chronic damage. Our data suggest a possible role of genetic background in determining the development of renal and neuropsychiatric damage, as demonstrated by the association with polymorphisms of TFNSF4 and MIR1279, respectively. These results agree with previous studies suggesting the involvement of TNFSF4 in Lupus nephritis and microRNA in neuroinflammation. Disclosure of Interests None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2022
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  • 7
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 75, No. Suppl 2 ( 2016-06), p. 279.2-280
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2016
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  • 8
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. Suppl 1 ( 2022-06), p. 541.2-541
    Abstract: Rheumatoid Arthritis (RA) is a multifactorial, chronic, systemic, inflammatory disease that can lead to progressive joint destruction (Alamanos et al, Autoimmun Rev 2005). Positivity for Rheumatoid Factor (RF) and antibodies against citrullinated proteins (ACPA) is useful for diagnostic and prognostic purposes. Nevertheless, in about 20% of patients, it is not possible to detect the presence of these autoantibodies. This has led to the identification of new antibody specificities, such as antibodies directed against carbamylated proteins (Mastrangelo A et al, J Immunol Res 2015) and, more recently, against homocysteinylated alpha 1 antitrypsin (anti-HATA) (Colasanti T et al, J Autoimmun 2020). Objectives To evaluate the prevalence of anti-HATA in a large cohort of patients with RA and their correlation with serological, clinical and erosive bone damage assessed by musculo-skeletal ultrasound (US). Methods Consecutive outpatients with RA, diagnosed according to the 2010 ACR/EULAR criteria, were enrolled. Demographic and clinical-laboratory data were recorded, including FR and ACPA determination. Disease activity was assessed by DAS28. The presence of anti-HATA antibodies was investigated by homemade ELISA using native alpha 1 antitrypsin modified in vitro to obtain homocysteinylated alpha 1 antitrypsin. US assessment was performed at the level of bilateral metacarpophalangeal and proximal interphalangeal joints; the presence of erosions and inflammatory features was identified according to OMERACT definitions (Wakefield RJ et al, J Rheumatol 2005). Results The present analysis included 91 RA patients (M/F 22/69; mean age 62 years; mean disease duration 12.5 years). Overall, the prevalence of anti-HATA was 69.2%. Anti-HATA antibodies were found in 63/91 (69.2%) of the entire patient cohort, whereas 68/91 (74.3%) patients were positive for ACPA and 63/91 (69.4%) for FR. 41.4% of patients had concomitant positivity for the three autoantibodies (FR, ACPA, anti-HATA). The analysis of patients with triple positivity for related arthritis antibodies (FR, ACPA, anti-HATA) was particularly interesting: indeed, in this subgroup, 80% of patients presented erosive damage, compared to 42.1% of patients who did not present simultaneously the three autoantibodies (p=0.0001). Patients with simultaneous positivity for RF, ACPA and anti-HATA showed a more aggressive disease phenotype (p=0.0001). Finally, a positive correlation was also found between disease activity (expressed by DAS28) and total inflammatory and erosive ultrasonographic score (p=0.005 and p=0.001, respectively). Conclusion The results of the present study confirm a high prevalence of anti-HATA in RA patients; furthermore, patients with concomitant presence of anti-HATA, ACPA and RF showed a more aggressive disease phenotype, in terms of erosive damage. Our analysis underlines as the characterization of new antibody specificities in RA could help in the early diagnosis of this disease and in the characterization of the different severity degrees. References [1]Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005 Mar;4(3):130-6. [2]Mastrangelo A, Colasanti T, Barbati C, Pecani A, Sabatinelli D, Pendolino M, Truglia S, Massaro L, Mancini R, Miranda F, Spinelli FR, Conti F, Alessandri C. The Role of Posttranslational Protein Modifications in Rheumatological Diseases: Focus on Rheumatoid Arthritis. J Immunol Res. 2015;2015:712490; [3]Colasanti T, Sabatinelli D, Mancone C, Giorgi A, Pecani A, Spinelli FR, Di Giamberardino A, Navarini L, Speziali M, Vomero M, Barbati C, Perricone C, Ceccarelli F, Finucci A, Celia AI, Currado D, Afeltra A, Schininà ME, Barnaba V, Conti F, Valesini G, Alessandri C. Homocysteinylated alpha 1 antitrypsin as an antigenic target of autoantibodies in seronegative rheumatoid arthritis patients. J Autoimmun. 2020 Sep;113:102470. [4]Wakefield RJ, Balint PV, Szkudlarek M, et al. Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheumatol 2005; 32: 2485-2487. Disclosure of Interests None declared.
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 1481557-6
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  • 9
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. Suppl 1 ( 2022-06), p. 1380.2-1381
    Abstract: Circulating endothelial progenitor cells (EPCs) are widely demonstrated biomarkers of endothelial function. Their frequency and function varied in systemic lupus erythematosus (SLE) patients, with a significant association with subclinical atherosclerosis 1 . Caffeine, one of the most widely consumed products in the world, seems to interact with multiple components of the immune system by acting as a non-specific phosphodiesterase inhibitor, and it seems to be able to activate autophagy 2-3 . In terms of cardiovascular disease (CVD), data from the literature showed a U-shaped association between habitual coffee intake and CVD 4 . In this view, Spyridopoulos et al. demonstrated a significant improvement in endothelial cells and EPCs migration after coffee consumption in coronary artery disease both in mouse models and in patients 5 . Finally, we demonstrated the impact of caffeine on SLE disease activity, in terms of SLEDAI2k values and serum cytokine levels. Moreover, patients with a low caffeine intake seemed to have a more severe disease phenotype 6 . Objectives The aim of this study was to evaluate the role of caffeine intake on endothelial function in SLE patients, by assessing its effect on number and function of EPCs both ex vivo in SLE patients and in vitro in healthy donors (HD) treated with SLE sera. Methods We performed a cross-sectional study enrolling consecutive SLE patients (revised 1997 ACR criteria), referring to the Sapienza Lupus Clinic. Patients with history of traditional CV risks factors were excluded. Caffeine intake was evaluated using a 7-day food frequency questionnaire. At the end of questionnaire filling circulating EPCs were detected by using a flow cytometry analysis defined as CD34+KDR+ cells. Subsequently, EPCs pooled from 6 HD were co-cultured with caffeine at 0.5 mM and 1 mM with and without SLE sera. After 7 days, we evaluated the cells morphology and the ability to form colonies. Moreover, we analyzed for the percentage of annexin V-positive (AV) apoptotic cells by flow cytometry analysis and for levels of autophagy and apoptotic markers LC3-II, p62 and Bcl2 by western blot. Results We enrolled 31 SLE patients (F:M 30:1, median age 43 years, IQR 18; median disease duration 144 months, IQR 180). The median intake of caffeine was 166 mg/day (IQR 194). We found a EPCs median percentage of 0.03% (IQR 0.04) observing a positive correlation between caffeine intake and EPCs percentage (p=0.03, r=0.4). Moving on in vitro experiments, after 7 days of cell cultures, HD EPCs treated with SLE sera and caffeine showed an improvement in morphology and in number of EPCs-CFU in comparison with those incubated with SLE sera without caffeine (p=0.0003). Moreover, the colonies treated with SLE sera were poorly organized in comparison with HD; the addition of caffeine restored the colony structure. After treated HD-EPCs with SLE sera we observed an increase in AV positive cells and p62 and LC3-II values and a reduction of Bcl2 values; the addition of caffeine was able to significantly reduce AV positive cells and p62 and LC3-II values and to significantly increased Bcl2 values, without any significant differences between caffeine 0.5 mM and 1 mM treatment (Figure 1A-D). Conclusion Our data demonstrated the ability of caffeine in increasing the number of circulating EPCs in SLE patients. Moreover, in vitro experiments seem to suggest a protective role of caffeine on EPCs survival and vitality through the promotion of autophagy and the inhibition of apoptosis. References [1]Westerweel et al. Ann Rheum Dis 2007; [2]Aronsen et al. Europ Joul of Pharm 2014; [3]Li et al. Theranostics 2018; [4]Ding et al. Circulation 2015; [5]Spyridopoulos et al. Art. Thromb Vasc Biol. 2008; [6]Orefice et al. Lupus 2020. Disclosure of Interests None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 1481557-6
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  • 10
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 73, No. Suppl 2 ( 2014-06), p. 532.2-532
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2014
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