scholarly journals POS0174 IMMUNOPHENOTYPE OF SJÖGREN´S SYNDROME AND SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS IDENTIFIED TWO ENDOTYPES WITH POTENTIAL THERAPEUTIC IMPLICATIONS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 300.1-300
Author(s):  
L. Martin-Gutierrez ◽  
J. Peng ◽  
G. Robinson ◽  
M. Naja ◽  
H. Peckham ◽  
...  
Keyword(s):  
Machine Learning ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
T Cell Subsets ◽  
Systemic Lupus ◽  
Immune Cell Subsets ◽  
Group 2 ◽  
Group 1

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

Serum uric acid as a predictor for nephritis in Egyptian patients with systemic lupus erythematosus

Lupus ◽  
2020 ◽  
pp. 096120332097904
Author(s):  
Eman Ahmed Hafez ◽  
Sameh Abd El-mottleb Hassan ◽  
Mohammed Abdel Monem Teama ◽  
Fatma Mohammed Badr
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Renal Function ◽  
Uric Acid ◽  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Group 2 ◽  
Group 1

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.

scholarly journals Cytokine clusters as potential diagnostic markers of disease activity and renal involvement in systemic lupus erythematosus

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052092688
Author(s):  
Joonhong Park ◽  
Woori Jang ◽  
Hye Sun Park ◽  
Ki Hyun Park ◽  
Seung-Ki Kwok ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cluster Analysis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Principal Component ◽  
Systemic Lupus ◽  
Group 2 ◽  
And Cluster Analysis ◽  
Group 1

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.

Identification and stratification of systemic lupus erythematosus patients into two transcriptionally distinct clusters based on IFN-I signature

Lupus ◽  
2021 ◽  
pp. 096120332199010
Author(s):  
Vineeta Shobha ◽  
Anu Mohan ◽  
AV Malini ◽  
Puneet Chopra ◽  
Preethi Karunanithi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Time Course ◽  
Cell Activation ◽  
Immune Cell ◽  
Gene Signature ◽  
Systemic Lupus ◽  
Auto Antibody ◽  
Activation Status

Objective Despite the significant advancement in the understanding of the pathophysiology of systemic lupus erythematosus (SLE) variable clinical response to newer therapies remain a major concern, especially for patients with lupus nephritis and neuropsychiatric systemic lupus erythematosus (NPSLE). We performed this study with an objective to comprehensively characterize Indian SLE patients with renal and neuropsychiatric manifestation with respect to their gene signature, cytokine profile and immune cell phenotypes. Methods We characterized 68 Indian SLE subjects with diverse clinical profiles and disease activity and tried to identify differentially expressed genes and enriched pathways. To understand the temporal profile, same patients were followed at 6 and 12-months intervals. Additionally, auto-antibody profile, levels of various chemokines, cytokines and the proportion of different immune cells and their activation status were captured in these subjects. Results Multiple IFN-related pathways were enriched with significant increase in IFN-I gene signature in SLE patients as compared to normal healthy volunteers (NHV). We identified two transcriptionally distinct clusters within the same cohort of SLE patients with differential immune cell activation status, auto-antibody as well as plasma chemokines and cytokines profile. Conclusions Identification of two distinct clusters of patients based on IFN-I signature provided new insights into the heterogeneity of underlying disease pathogenesis of Indian SLE cohort. Importantly, patient within those clusters retain their distinct expression dynamics of IFN-I signature over the time course of one year despite change in disease activity. This study will guide clinicians and researchers while designing future clinical trials on Indian SLE cohort.

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
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Serum Amyloid A ◽  
Serum Levels ◽  
Innate Immune ◽  
Pentraxin 3 ◽  
Systemic Lupus ◽  
Amyloid A ◽  
Group 2 ◽  
Group 1

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

scholarly journals CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Nur Diyana Mohd Shukri ◽  
Aziz Farah Izati ◽  
Wan Syamimee Wan Ghazali ◽  
Che Maraina Che Hussin ◽  
Kah Keng Wong
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Lymphocyte Subpopulations ◽  
Gene Set Enrichment Analysis ◽  
T Cell Subsets ◽  
Healthy Controls ◽  
Systemic Lupus

The receptors for IL-35, IL-12Rβ2 and gp130, have been implicated in the inflammatory pathophysiology of autoimmune diseases. In this study, we set out to investigate the serum IL-35 levels and the surface levels of IL-12Rβ2 and gp130 in CD3+CD4+, CD3+CD4─ and CD3─CD4─ lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients (n=50) versus healthy controls (n=50). The potential T cell subsets associated with gp130 transcript (i.e. IL6ST) expression in CD4+ T cells of SLE patients was also examined in publicly-available gene expression profiling (GEP) datasets. Here, we report that serum IL-35 levels were significantly higher in SLE patients than healthy controls (p=0.038) but it was not associated with SLEDAI-2K scores. The proportions of IL-12Rβ2+ and gp130+ cells in SLE patients did not differ significantly with those of healthy controls in all lymphocyte subpopulations investigated. Essentially, higher SLEDAI-2K scores were positively correlated with increased proportion of gp130+ cells, but not IL-12Rβ2+ cells, on CD3+CD4+ T cells (r=0.425, p=0.002, q=0.016). Gene Set Enrichment Analysis (GSEA) of a GEP dataset of CD4+ T cells isolated from SLE patients (n=8; GSE4588) showed that IL6ST expression was positively associated with genes upregulated in CD4+ T cells vs myeloid or B cells (q&lt;0.001). In an independent GEP dataset of CD4+ T cells isolated from SLE patients (n=9; GSE1057), IL6ST expression was induced upon anti-CD3 stimulation, and that Treg, TCM and CCR7+ T cells gene sets were significantly enriched (q&lt;0.05) by genes highly correlated with IL6ST expression (n=92 genes; r&gt;0.75 with IL6ST expression) upon anti-CD3 stimulation in these SLE patients. In conclusion, gp130 signaling in CD3+CD4+ T cell subsets may contribute to increased disease activity in SLE patients, and it represents a promising therapeutic target for inhibition in the disease.

scholarly journals Involvement of lncRNA IL21-AS1 in interleukin-2 and T follicular regulatory cell activation in systemic lupus erythematosus

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
He Hao ◽  
Shingo Nakayamada ◽  
Naoaki Ohkubo ◽  
Kaoru Yamagata ◽  
Mingzeng Zhang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
T Cell Subsets ◽  
Mrna Levels ◽  
Systemic Lupus ◽  
Allelic Discrimination

Abstract Background The single nucleotide polymorphism (SNP) rs62324212, located in IL21 antisense RNA 1 (IL21-AS1), has been identified as a genetic risk variant associated with systemic lupus erythematosus (SLE). We aimed to probe the characteristics of IL21-AS1 and explore its clinical relevance focusing on T helper subsets and disease activity in patients with SLE. Methods rs62324212 genotyping was determined using allelic discrimination by quantitative PCR. Gene expression in peripheral blood mononuclear cells and cell surface markers in CD4+ T cells were analyzed using PCR and flow cytometry. The association among IL21-AS1, CD4+ T cell subsets, and SLE disease activity was accessed. Results Ensembl Genome Browser analysis revealed that rs62324212 (C>A) was located in the predicting enhancer region of IL21-AS1. IL21-AS1 was expressed in the nucleus of CD4+ T and B cells, but its expression was decreased in patients with SLE. IL21-AS1 expression was positively correlated with mRNA levels of IL-2 but not IL-21, and it was associated with the proportion of activated T follicular regulatory (Tfr) cells. Furthermore, we observed a significant negative correlation between IL21-AS1 expression and disease activity in patients with SLE (n = 53, p < 0.05). Conclusion IL21-AS1 has an effect on disease activity through an involvement of IL-2-mediated activation of Tfr cells in SLE. Thus, targeting the IL21-AS1 may provide therapeutic approaches for SLE.

Involvement of lncRNA IL21-AS1 in Interleukin-2 and T Follicular Regulatory Cell Activation in Systemic Lupus Erythematosus

2021 ◽  
Author(s):  
He Hao ◽  
Shingo Nakayamada ◽  
Naoaki Ohkubo ◽  
Kaoru Yamagata ◽  
Mingzeng Zhang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
T Cell Subsets ◽  
Mrna Levels ◽  
Systemic Lupus ◽  
Allelic Discrimination

Abstract Background The single nucleotide polymorphism (SNP) rs62324212, located in IL21 antisense RNA 1 (IL21-AS1), has been identified as a genetic risk variant associated with systemic lupus erythematosus (SLE). We aimed to probe the characteristics of IL21-AS1 and explore its clinical relevance focusing T helper subsets and disease activity in patients with SLE. Methods rs62324212 genotyping was determined using allelic discrimination by quantitative PCR. Gene expression in peripheral blood mononuclear cells and cell surface markers in CD4+ T cells were analyzed using PCR and flow cytometry. The association among IL21-AS1, CD4+ T cell subsets and SLE disease activity were accessed. Results Ensembl Genome Browser analysis revealed that rs62324212 (C > A) was located in the predicting enhancer region of IL21-AS1. IL21-AS1 was expressed in the nucleus of CD4+ T and B cells, but its expression was decreased in patients with SLE. IL21-AS1 expression was positively correlated with mRNA levels of IL-2 but not IL-21, and it was associated with the proportion of activated T follicular regulatory (Tfr) cells. Furthermore, we observed a significant negative correlation between IL21-AS1 expression and disease activity in patients with SLE (n = 53, p < 0.05). Conclusion IL21-AS1 has an effect on disease activity through an impairment of IL-2-mediated activation of Tfr cell in SLE. Thus, targeting the IL21-AS1 may provide therapeutic approaches for SLE.

Repeated administration of dapirolizumab pegol in a randomised phase I study is well tolerated and accompanied by improvements in several composite measures of systemic lupus erythematosus disease activity and changes in whole blood transcriptomic profiles

2017 ◽  
Vol 76 (11) ◽  
pp. 1837-1844 ◽  
Author(s):  
Chris Chamberlain ◽  
Peter J Colman ◽  
Ann M Ranger ◽  
Linda C Burkly ◽  
Geoffrey I Johnston ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Adverse Events ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Repeated Administration ◽  
Clinical Activity ◽  
Systemic Lupus ◽  
Fab Fragment ◽  
Double Blind

ObjectivesSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with diffuse immune cell dysfunction. CD40–CD40 ligand (CD40L) interaction activates B cells, antigen-presenting cells and platelets. CD40L blockade might provide an innovative treatment for systemic autoimmune disorders. We investigated the safety and clinical activity of dapirolizumab pegol, a polyethylene glycol conjugated anti-CD40L Fab' fragment, in patients with SLE.MethodsThis 32-week randomised, double-blind, multicentre study (NCT01764594) evaluated repeated intravenous administration of dapirolizumab pegol in patients with SLE who were positive for/had history of antidouble stranded DNA/antinuclear antibodies and were on stable doses of immunomodulatory therapies (if applicable). Sixteen patients were randomised to 30 mg/kg dapirolizumab pegol followed by 15 mg/kg every 2 weeks for 10 weeks; eight patients received a matched placebo regimen. Randomisation was stratified by evidence of antiphospholipid antibodies. Patients were followed for 18 weeks after the final dose.ResultsNo serious treatment-emergent adverse events, thromboembolic events or deaths occurred. Adverse events were mild or moderate, transient and resolved without intervention. One patient withdrew due to infection.Efficacy assessments were conducted only in patients with high disease activity at baseline. Five of 11 (46%) dapirolizumab pegol-treated patients achieved British Isles Lupus Assessment Group-based Composite Lupus Assessment response (vs 1/7; 14% placebo) and 5/12 (42%) evaluable for SLE Responder Index-4 responded by week 12 (vs 1/7; 14% placebo). Mechanism-related gene expression changes were observed in blood RNA samples.ConclusionsDapirolizumab pegol could be an effective biological treatment for SLE. Further studies are required to address efficacy and safety.Trial registration numberNCT01764594.

scholarly journals AB0138 INCREASED CD38 EXPRESSION LEVELS ON IMMUNE CELL SUBSETS IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1369.2-1370
Author(s):  
L. Ostendorf ◽  
P. Enghard ◽  
P. Durek ◽  
F. Heinrich ◽  
M. F. Mashreghi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Lymphocytes ◽  
Lupus Erythematosus ◽  
Plasma Cells ◽  
Immune Cell ◽  
Systemic Lupus ◽  
Cd38 Expression ◽  
Cd8 T Lymphocytes ◽  
Immune Cell Subsets

Background:Plasma Cells (PCs) are implicated in the pathogenesis of Systemic Lupus erythematosus (SLE) and their targeting proved a promising treatment modality. As there is a monoclonal therapeutic antibody targeting CD38 licensed for clinical use in multiple myeloma, plasma cell depletion via CD38 seems to represent a promising path in SLE treatment. While CD38 Is highly expressed on plasmacells, it is present on the surface of subsets of T and B lymphocytes as well as myeloid cells.Objectives:Here we aim to identify the differential expression of CD38 on peripheral blood leukocytes in SLE compared to healthy controls (HC) investigate the function of CD38+ T lymphocytesMethods:We performed flow cytometry to investigate the expression of CD38 on peripheral blood mononuclear cells of SLE patients (n=36) and HCs (n=20). We additionally analyzed the expression of T lymphocytes within the urine of patients with lupus nephritis as well as the skin of SLE patients. We investigated the inflammatory potential of CD38 positive memory T lymphocytes after stimulation and performed single-cell RNA sequencing analyses.Results:CD38 Expression is increased on certain immune cell subsets: Plasmablasts and unswitched Memory B cells, as well as plasmacytoid dendritic cells and CD16+ non-classical monocytes. We observed a drastic increase CD38 in both memory CD4 and CD8 T lymphocytes in SLE patients. These cells were mostly effector T cells (and not regulatory T cells) and expressed other markers of T cell activation and proliferation. We found an enrichment of CD38+ memory T cells in the urine of patients with lupus nephritis. After polyclonal stimulation of T cells, CD38+ produced less inflammatory cytokines. Preliminary single-cell sequencing results indicate that CD38+ CD8+ T-lymphocytes have decreased clonal diversity and that these cells express genes associated with exhaustion and type 1 interferon response.Conclusion:Increased CD38 expression on various lymphocyte subsets provides an additional rationale for investigating CD38-directed therapies in SLE. Targeting CD38 could not only deplete plasma cells but also has the potential to target interferon alpha producing plasmacytoid dendritic cells and modulate inflammatory T cell functions.Disclosure of Interests:Lennard Ostendorf: None declared, Philipp Enghard: None declared, Pawel Durek: None declared, Frederik Heinrich: None declared, Mir-Farzin Mashreghi: None declared, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Andreas Radbruch: None declared, Falk Hiepe: None declared, Tobias Alexander: None declared

scholarly journals Relevant Characteristics Analysis Using Natural Language Processing and Machine Learning Based on Phenotypes and T-Cell Subsets in Systemic Lupus Erythematosus Patients With Anxiety

2021 ◽  
Vol 12 ◽  
Author(s):  
Xi-xi Gu ◽  
Yi Jin ◽  
Ting Fu ◽  
Xiao-ming Zhang ◽  
Teng Li ◽  
...  
Keyword(s):  
Machine Learning ◽  
Systemic Lupus Erythematosus ◽  
Natural Language Processing ◽  
T Cell ◽  
B Cell ◽  
Language Processing ◽  
Lupus Erythematosus ◽  
T Cell Subsets ◽  
Systemic Lupus ◽  
B Cell Subsets

Anxiety is frequently observed in patients with systemic lupus erythematosus (SLE) and the immune system could act as a trigger for anxiety. To recognize abnormal T-cell and B-cell subsets for SLE patients with anxiety, in this study, patient disease phenotypes data from electronic lupus symptom records were extracted by using natural language processing. The Hospital Anxiety and Depression Scale (HADS) was used to distinguish patients, and 107 patients were selected to meet research requirements. Then, peripheral blood was collected from two patient groups for multicolor flow cytometry experiments. The characteristics of 75 T-cell and 15 B-cell subsets were investigated between SLE patients with- (n = 23) and without-anxiety (n = 84) groups by four machine learning methods. The findings showed 13 T-cell subsets were significantly different between the two groups. Furthermore, BMI, fatigue, depression, unstable emotions, CD27+CD28+ Th/Treg, CD27−CD28− Th/Treg, CD45RA−CD27− Th, and CD45RA+HLADR+ Th cells may be important characteristics between SLE patients with- and without-anxiety groups. The findings not only point out the difference of T-cell subsets in SLE patients with or without anxiety, but also imply that T cells might play the important role in patients with anxiety disorder.

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