scholarly journals AB0051 SERUM AMYLOID A AND PENTRAXIN 3: INNATE IMMUNE RESPONSE AND DISEASE ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1328.1-1328
Author(s):  
R. Assandri ◽  
G. Martellosio ◽  
A. Montanelli

Background:Systemic Lupus Erythematosus (SLE) is an autoimmune disease that involves several molecular patterns with a wide spectrum of clinical manifestations and symptoms. Inflammation and related pathway play a role in SLE pathogenesis. The pentraxin superfamily including long and short pentraxin, C Reactive Protein CRP, Serum amyloid A (SAA), Pentraxin 3 (PTX3) are key components of innate immune system and induce a variety of inflammation associated pathway. However Literature provides several evidences that CRP serum levels not correlated with clinical and immunological manifestations. This situation affected clinical practice and the patient follow up. PTX3 have been identified as a component of inflammatory status in several autoimmune conditions. SAA is an acute phase protein secreted in large quantity during inflammation.Objectives:We want to evaluated SAA, PTX3 and CRP concentrations, their correlation between SLE Disease Activity Index (SLEDAI), that including complement fractions C3, C4.Methods:We enrolled fifty patients that fulfilled the SLE American College of Rheumatology criteria and fifty healthy subjects. The SLE disease activity was classified with the SLEDAI (0 to 12). Patients were divided into two groups according to SLEDAI score: inactive group (Group 1, 25 patients, 50%: SLEDAI < 4) and active group (Group 2, 25 patients, 50%: SLEDAI 5 to 12). PTX3 concentration was measured by a sandwich ELISA kit (Hycult) with 2.8 ng/mL cut-off point. SAA concentration was detected by nephelometry performed on a BN ProSpec System (Siemens, Germany), with assay kit based on polyclonal antibodies (Siemens Healthcare Diagnostics Products, Germany, 6.5 mg/L cut-off point). High sensitive CRP concentrations were determined using the ci8200 platform (Abbott Laboratories Chicago, Illinois).Results:Plasma PTX3 and serum SAA levels was significantly higher in SLE patients than in the healthy subjects (PTX311.5 ± 7.3 ng/mL vs 2.3 ± 1.1; p < 0.001; SAA: 87 ±77 mg/L vs 2.6±2.5; p < 0.001). These differences were not evident in CRP levels (8.5 ± 7.8 mg/L vs 6.2± 2.5). Considering two groups, there were statistical differences in PTX3 level (Group 2: 14.9 ± 12 ng/mL vs Group 1: 2.16 ±0.5 ng/mL, p<0,05) and SAA concentration (Group 2: 114 ± 89 ng/mL vs Group 1: 3.6 ±1.7 ng/mL, p<0,05) but not in CRP concentration (Group 2: 11.5 ± 8.4 mg/L vs Group 1: 9.5 ±3.5). There was a significantly negative correlation between C3, C4 fractions, PTX3 and SSA levels (respectively r = −0.74, p=<0.05, and r = −0.79, p<0.05). No statistical correlation were appeared between C3, C4 fractions and CRP serum levels (r= −0,12., p= 0.82, and r= −0.18, p= 0,21). We noted a positive significant correlation between SLEDAI, PTX3 and SAA concentration (r = 0.79, p < 0.05, 0.83, p < 0.05, respectively) an increase in PTX3 and SAA levels followed the lupus flare and symptoms. No significant correlation appeared between SLEDAI and CRP (r= 0.15, p=0.89)Conclusion:PTX3 and SAA concentration was significantly higher in SLE patients than the healthy control subjects and their levels reflected disease activity. We showed a direct correlation between PTX3 and SAA. In SLE patients PTX3 and SAA concentrations were correlated with SLEDAI. We suggest an integrate viewpoint in witch SAA and PTX3 may play a role as a biomarker of disease activity, with synergic work during SLE events. Evidences suggested that PTX3 and SAA could trigger the same molecular pathway, by TLR4, via NF-kB.References:[1]Assandri R, Monari M Montanelli A. Pentraxin 3 in Systemic Lupus Erithematosus: Questions to be Resolved, Translational Biomedicine (2015)Disclosure of Interests:None declared

Lupus ◽  
2020 ◽  
pp. 096120332097904
Author(s):  
Eman Ahmed Hafez ◽  
Sameh Abd El-mottleb Hassan ◽  
Mohammed Abdel Monem Teama ◽  
Fatma Mohammed Badr

Objective Lupus nephritis (LN) is closely associated with hyperuricemia, and uric acid is considered a risk factor for renal involvement in systemic lupus erythematosus (SLE). This study aimed to examine the association between serum uric acid (SUA) level and LN development and progression in SLE patients with normal renal function. Methods A total of 60 SLE patients with normal renal function from Ain Shams University Hospital were selected and assigned to group 1 (30 patients with LN) and group 2 (30 patients without LN). All patients were subjected to history taking, clinical examination, disease activity assessment based on SLE disease activity index (SLEDAI) and renal SLEDAI (SLEDAI-R) scores, and laboratory investigations, including as SUA, complete blood count, blood urea nitrogen (BUN), serum creatinine, creatinine clearance, urine analysis, protein/creatinine ratio, 24-h urinary protein excretion, Antinuclear antibodies (ANA), anti-dsDNA antibody, and serum complement (C3, C4). Results Disease duration, SLEDAI score, and SUA level were higher in group 1 than in group 2 (p < 0.001). SUA level was positively correlated with SLEDAI and SLEDAI-R scores, proteinuria, urinary casts, renal biopsy class, disease activity and chronicity indices, BUN level, and serum creatinine level but was negatively correlated with creatinine clearance (p < 0.05). SUA was a predictor of LN development in SLE patients (sensitivity, 83.3%; specificity, 70%). Conclusion SUA is associated with the development of lupus nephritis in patients with normal kidney function also SUA in-dependently correlated with disease activity and chronicity in LN.


2020 ◽  
Vol 48 (6) ◽  
pp. 030006052092688
Author(s):  
Joonhong Park ◽  
Woori Jang ◽  
Hye Sun Park ◽  
Ki Hyun Park ◽  
Seung-Ki Kwok ◽  
...  

Objective To describe interactions among cytokines and to identify subgroups of systemic lupus erythematosus (SLE) patients based on cytokine levels using principal component analysis and cluster analysis. Methods Levels of 12 cytokines were measured using sensitive multiplex bead assays and associations with SLE features including disease activity and renal involvement were assessed. Results In a group of 203 SLE patients, strong correlations were observed between interleukin (IL)6 and interferon (IFN)γ levels (r = 0.624), IL17 and IFNγ levels (r = 0.768), and macrophage inflammatory protein (MIP)1α and MIP1β levels (r = 0.675). Cluster analysis revealed two distinct patient groups characterized by high levels of IL8, MIP1α, and MIP1β (group 1) or of IL2, IL6, IL10, IL12, IFNγ, and tumor necrosis factor α (group 2). Active disease was more common in group 1 (49/88, 55.7%) than in group 2 (40/115, 34.8%). More patients in group 2 had renal involvement (42/115, 36.5%) than in group 1 (22/88, 25%). Conclusions Assessment of cytokine profiles can identify distinct SLE patient subgroups and aid in understanding clinical heterogeneity and immunological phenotypes.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1005.1-1006
Author(s):  
M. Liu ◽  
Y. Huang ◽  
Z. Huang ◽  
Q. Huang ◽  
T. W. Li

Background:Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease characterized by excessive production of immune complexes and proinflammatory cytokine. Low complement, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have been used as inflammatory biomarkers to assess the disease activity of SLE. Recently, the fibrinogen to albumin ratio (FAR) has emerged as an effective indicator to reflect the systemic inflammation in many diseases. However, the role of FAR in SLE has been scarcely studied.Objectives:This study was to investigate the association between FAR and SLE Disease Activity Index 2000 (SLEDAI-2K) in SLE.Methods:This retrospective study included 74 SLE patients and 79 age- and sex-matched healthy subjects. According to the SLEDAI-2K score, SLE patients were divided into Group 1 with a score ≤ 9 (patients with mild disease activity, N = 41) and Group 2 with a score > 9 (patients with moderate to severe disease activity, N = 33). Neutrophil, lymphocyte, monocyte, platelet, albumin, fibrinogen, NLR, PLR, monocyte to lymphocyte ratio (MLR), FAR, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), complement 3 (C3), complement 4 (C4) and SLEDAI-2K were collected. Receiver operation characteristic (ROC) curves were conducted to discriminate SLE patients from healthy controls and SLE patients with different disease activity. Correlations between the inflammatory markers and SLEDAI-2K were analyzed.Results:FAR, NLR, PLR, MLR and fibrinogen in SLE patients were higher compared to those of the healthy controls (P < 0.05), while albumin was lower (P < 0.05). Patients in Group 2 had higher levels of FAR, NLR, PLR, fibrinogen and CRP than those in Group 1 (P < 0.05) except MLR (P = 0.579) and ESR (P = 0.130), albumin and C3 were lower (P < 0.05). Furthermore, FAR were higher in SLE patients with nephritis than those without nephritis (P = 0.009). The ROC curve for differentiating SLE patients from healthy individuals showed that the area under curve (AUC) of FAR (0.801, 95%CI: 0.728 - 0.874) and albumin (0.833, 95%CI: 0.764-0.903) were higher than NLR (0.798, 95%CI: 0.725 - 0.871), PLR (0.680, 95%CI: 0.588 - 0.771), MLR (0.785, 95%CI: 0.712 - 0.859) and fibrinogen (0.645, 95%CI: 0.556 - 0.733). Besides, the ROC curve for predicting the disease activity of SLE patients indicated that the AUC of FAR (0.911, 95%CI: 0. 842 - 0.980) was higher than NLR (0.697, 95%CI: 0.574 - 0.821), PLR (0.695, 95%CI: 0.571 - 0.820), MLR (0.553, 95%CI: 0.415 - 0.691), fibrinogen (0.718, 95%CI: 0.590 - 0.847), CRP (0.672, 95%CI: 0.540 - 0.803), ESR (0.640, 95%CI: 0.510 - 0.770), C3 (0.644, 95%CI: 0.515 - 0.773), C4 (0.544, 95%CI: 0.407 - 0.681) and albumin (0.894, 95%CI: 0.819 - 0.969). FAR was positively correlated with SLEDAI-2K (r = 0.682, P < 0.001), yielding a highest relevance than other inflammatory parameters.Conclusion:FAR was significantly elevated in SLE patients compared with healthy subjects and related with the disease activity of SLE. FAR might be a useful inflammatory index to evaluate disease activity in patients with SLE.References:[1]Liu M, Huang Y, Huang Z, Zhong Z, Deng W, Huang Z, et al. The role of fibrinogen to albumin ratio in ankylosing spondylitis: Correlation with disease activity. Clin Chim Acta. 2020 Jun; 505:136-140.Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 300.1-300
Author(s):  
L. Martin-Gutierrez ◽  
J. Peng ◽  
G. Robinson ◽  
M. Naja ◽  
H. Peckham ◽  
...  

Background:Primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE) are chronic autoimmune rheumatic diseases (ARDs) that share a strong female gender bias, as well as genetic, clinical and serological characteristics.Although significant progress has been made in improving treatment and patient related outcomes in pSS and SLE, there is a need for improved early diagnosis, adequate therapy monitoring, treatment of refractory manifestations and strategies to address co-morbidities.However, the results of many clinical trials are disappointing, and nobiologic treatments are licensedin pSS, while few are available for SLE patients with refractory disease.Objectives:Identifying shared immunological features between patients with pSS and SLE that could lead to better treatment selection using a stratification approach.Methods:Immune-phenotyping of 29 immune-cell subsets in peripheral blood from patients with pSS (n=45), SLE (n=29) and secondary SS associated with SLE (SLE/SS) (n=14) with low disease activity or in clinical remission, and sex-matched healthy controls (n=31), was performed using flow cytometry. Data were analysed using logistic regression and multiple t-tests andsupervised machine learning (balanced random forest-BRF, sparse partial least squares discriminant analysis-sPLS-DA). Patients were stratified by k-means clustering. Clinical trajectories were analysed over 5 year follow-up.Results:Comparing the immune profile of pSS and SLE patients using a variety of statistical and machine learning (ML) approaches, identified very few statistically significant differences between the two cohorts despite patients having a different clinical presentation and diagnosis. Thus, we hypothesised that immune-based subtypes could be shared between pSS, SLE and SLE/SS patients. Unsupervised k-means clustering was applied to the immunological features of the combined patient cohorts and two distinct patient endotypes, were identified: Group-1 (n=49; pSS=24, SLE=19, SLE/SS=6) and Group-2 (n=39; pSS=21, SLE=10, SLE/SS=8). Significant differences in immune-cell phenotypes across B-cell and T-cell subsets were identified by logistic regression, BRF (AUC=0.9942, assessed by 10-fold cross-validation) and sPLS-DA analysis. Comparison of the multiple analysis approaches identified eight common immune-cell subsets, including total and memory CD4+ and CD8+ T-cell subsets but no B-cell subsets. Using this common immune-signature the stratification between the groups was maintained and slightly improved (AUC=0.9979 and accuracy 96.16%). Interestingly, patients in Group-2 had elevated disease activity measures at baseline and over a 5-year trajectory compared to Group-1. Finally, correlation analysis identifed correlations between disease activity markers and the top ranked immune features from the ML models.Conclusion:The identified immune-cell signatures could reflect the underlying disease pathogenesis that spans diagnositc criteria and could be used to select patients for targeted therapeutic approaches.Acknowledgements:LM-G is supported by a project grant from The Dunhill Medical Trust (RPGF1902\117); JP is supported by Versus Arthritis (21226). GAR is supported by Lupus UK, The Rosetrees Trust (M409) and Versus Arthritis (21593). MN is supported by NIHR UCLH Biomedical Research Centre (BRC525/III/CC/191350). HP has a Versus Arthritis PhD studentship (22203). This work was performed within the Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH supported by grants from Versus Arthritis (21593 and 20164), GOSCC, and the NIHR-Biomedical Research Centres at both GOSH and UCLH.We would like to thank Mr Jamie Evans for expert support with flow cytometry analysis and Ms Eve McLoughlin for support with patient recruitment.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 340.2-341
Author(s):  
V. Orefice ◽  
F. Ceccarelli ◽  
C. Barbati ◽  
R. Lucchetti ◽  
G. Olivieri ◽  
...  

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease mainly affecting women of childbearing age. The interplay between genetic and environmental factors may contribute to disease pathogenesis1. At today, no robust data are available about the possible contribute of diet in SLE. 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 inhibitor2.In vitrodose-dependent treatment with caffeine seems to down-regulate mRNA levels of key inflammation-related genes and similarly reduce levels of different pro-inflammatory cytokines3.Objectives:We evaluated the impact of caffeine consumption on SLE-related disease phenotype and activity, in terms of clinimetric assessment and cytokines levels.Methods:We performed a cross-sectional study, enrolling consecutive patients and reporting their clinical and laboratory data. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2k)4. Caffeine intake was evaluated by a 7-day food frequency questionnaire, including all the main sources of caffeine. As previously reported, patients were divided in four groups according to the daily caffeine intake: <29.1 mg/day (group 1), 29.2-153.7 mg/day (group 2), 153.8-376.5 mg/day (group 3) and >376.6 mg/day (group 4)5. At the end of questionnaire filling, blood samples were collected from each patient to assess cytokines levels. These were assessed by using a panel by Bio-Plex assays to measure the levels of IL-6, IL-10, IL-17, IL-27, IFN-γ, IFN-α and Blys.Results:We enrolled 89 SLE patients (F/M 87/2, median age 46 years, IQR 14; median disease duration 144 months, IQR 150). The median intake of caffeine was 195 mg/day (IQR 160.5). At the time of the enrollment, 8 patients (8.9%) referred a caffeine intake < 29.1 mg/day (group 1), 27 patients (30.3%) between 29.2 and 153.7 mg/day (group 2), 45 patients (51%) between 153.8 and 376.5 mg/day (group 3) and 9 patients (10.1%) >376.6 mg/day (group 4). A negative correlation between the levels of caffeine and disease activity, evaluated with SLEDAI-2K, was observed (p=0.01, r=-0.26). By comparing the four groups, a significant higher prevalence of lupus nephritis, neuropsychiatric involvement, haematological manifestations, hypocomplementemia and anti-dsDNA positivity was observed in patients with less intake of caffeine (figure 1 A-E). Furthermore, patients with less intake of caffeine showed a significant more frequent use of glucocorticoids [group 4: 22.2%,versusgroup 1 (50.0%, p=0.0001), group 2 (55.5%, p=0.0001), group 3 (40.0%, p=0.009)]. Moving on cytokines analysis, a negative correlation between daily caffeine consumption and serum level of IFNγ was found (p=0.03, r=-0.2) (figure 2A); furthermore, patients with more caffeine intake showed significant lower levels of IFNα (p=0.02, figure 2B), IL-17 (p=0.01, figure 2C) and IL-6 (p=0.003, figure 2D).Conclusion:This is the first report demonstrating the impact of caffeine on SLE disease activity status, as demonstrated by the inverse correlation between its intake and both SLEDAI-2k values and cytokines levels. Moreover, in our cohort, patients with less caffeine consumption seems to have a more severe disease phenotype, especially in terms of renal and neuropsychiatric involvement. Our results seem to suggest a possible immunoregulatory dose-dependent effect of caffeine, through the modulation of serum cytokine levels, as already suggested byin vitroanalysis.References:[1]Kaul et alNat. Rev. Dis. Prim.2016; 2. Aronsen et alEurop Joul of Pharm2014; 3. Iris et alClin Immun.2018; 4. Gladman et al J Rheumatol. 2002; 5. Mikuls et alArth Rheum2002Disclosure of Interests:Valeria Orefice: None declared, Fulvia Ceccarelli: None declared, cristiana barbati: None declared, Ramona Lucchetti: None declared, Giulio Olivieri: None declared, enrica cipriano: None declared, Francesco Natalucci: None declared, Carlo Perricone: 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, Guido Valesini: None declared, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi


Pteridines ◽  
2020 ◽  
Vol 31 (1) ◽  
pp. 185-192
Author(s):  
Deniz Öğütmen Koç ◽  
Hande Sipahi ◽  
Cemile Dilşah Sürmeli ◽  
Mustafa Çalık ◽  
Nilgün Bireroğlu ◽  
...  

AbstractIn Coronavirus disease 2019 (COVID-19), it is important to evaluate disease activity and investigate possible biomarkers. Therefore, in this study, we investigated the relationship between disease activity and serum levels of possible immune activation marker neopterin in patients with COVID-19. The study enrolled 45 patients (23 females, 51.1%) treated for COVID-19. The patients were divided into two groups according to their clinical presentation: those who recovered quickly (Group 1) and those who worsened progressively (Group 2). The neopterin and C-reactive protein levels were high in all patients on admission. In Group 1, neopterin concentrations and serum neopterin/creatinine ratios were significantly higher on admission compared to Day 14 of the disease, whereas in Group 2, levels were significantly higher at Day 14 of the disease than on admission. Neopterin levels at admission were significantly higher in Group 1. The serum neopterin concentrations at admission were markedly higher in patients with a derived neutrophil–lymphocyte ratio (dNLR) > 2.8 compared to those with a dNLR ≤ 2.8 (p < 0.05). Serum neopterin levels can be used as a prognostic biomarker in predicting disease activity in COVID-19.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Conti Fabrizio ◽  
Ceccarelli Fulvia ◽  
Perricone Carlo ◽  
Massaro Laura ◽  
Marocchi Elisa ◽  
...  

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status.Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM).Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.;P=0.001). Serositis resulted significantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.;P<0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA − (21.8%,P=0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P=0.7).Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.


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