scholarly journals Ethnicity-specific transcriptomic variation in immune cells and correlation with disease activity in systemic lupus erythematosus

2020 ◽  
Author(s):  
Gaia Andreoletti ◽  
Cristina M. Lanata ◽  
Ishan Paranjpe ◽  
Tia S. Jain ◽  
Joanne Nititham ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
B Cells ◽  
Disease Activity ◽  
Nk Cells ◽  
Differentially Expressed Genes ◽  
Lupus Erythematosus ◽  
Differentially Expressed ◽  
Cell Type ◽  
Systemic Lupus

AbstractSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease in which outcomes vary among different racial groups. The aim of this study is to leverage large-scale transcriptomic data from diverse populations to better sub-classify SLE patients into more clinically actionable groups. We leverage cell sorted RNA-seq data (CD14+ monocytes, B cells, CD4+T cells, and NK cells) from 120 SLE patients (63 Asian and 57 White individuals) and apply a four tier analytical approach to identify SLE subgroups within this multiethnic cohort: unsupervised clustering, differential expression analyses, gene co-expression analyses, and machine learning. K-means clustering on the individual cell type data resulted in three clusters for CD4 and CD14, and two clusters for B cells and NK cells. Correlation analysis revealed significant positive associations between the transcriptomic clusters of each immune cell and clinical parameters including disease activity and ethnicity. We then explored differentially expressed genes between Asian and White groups for each cell-type. The shared differentially expressed genes across the four cell types were involved in SLE or other autoimmune related pathways. Co-expression analysis identified similarly regulated genes across samples and grouped these genes into modules. Samples were grouped into White-high, Asians-high (high disease activity defined by SLEDAI score >=6) and White-low, Asians-low (SLEDAI < 6). Random forest classification of disease activity in the White and Asian cohorts showed the best classification in CD4+ T cells in White. The results from these analyses will help stratify patients based on their gene expression signatures to enable precision medicine for SLE.

scholarly journals Ethnicity-specific transcriptomic variation in immune cells and correlation with disease activity in systemic lupus erythematosus

2020 ◽  
Author(s):  
Gaia Andreoletti ◽  
Cristina Lanata ◽  
Ishan Paranjpe ◽  
Tia Jain ◽  
Joanne Nititham ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Disease Activity ◽  
Nk Cells ◽  
Differentially Expressed Genes ◽  
Lupus Erythematosus ◽  
Cd4 T Cells ◽  
Differentially Expressed ◽  
Cell Type ◽  
Systemic Lupus

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease in which outcomes vary among different racial groups. We leverage cell-sorted RNA-seq data (CD14 + monocytes, B cells, CD4 + T cells, and NK cells) from 120 SLE patients (63 Asian and 57 White individuals) and apply a four-tier approach to identify SLE subgroups within this multiethnic cohort: unsupervised clustering, differential expression analyses, gene co-expression analyses, and machine learning. K-means clustering on each cell-type resulted in three clusters for CD4 and CD14, and two for B and NK cells. Correlation analysis revealed significant positive associations between the transcriptomic clusters and clinical parameters including disease activity and ethnicity. We then explored differentially expressed genes between Asian and White groups for each cell-type. The shared differentially expressed genes across all cells were involved in SLE or other autoimmune-related pathways. Co-expression analysis identified similarly regulated genes across samples and grouped these genes into modules. Samples were grouped into groups base on their disease activity and ethnicity. Random forest classification of disease activity in the White and Asian cohorts showed the best classification in CD4 + T cells in White. The results from these analyses will help stratify patients based on their gene expression signatures to enable SLE precision medicine.

scholarly journals Transcriptomic analysis of immune cells in a multi-ethnic cohort of systemic lupus erythematosus patients identifies ethnicity- and disease-specific expression signatures

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Gaia Andreoletti ◽  
Cristina M. Lanata ◽  
Laura Trupin ◽  
Ishan Paranjpe ◽  
Tia S. Jain ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Disease Activity ◽  
Nk Cells ◽  
Differentially Expressed Genes ◽  
Lupus Erythematosus ◽  
Cd4 T Cells ◽  
Differentially Expressed ◽  
Cell Type ◽  
Systemic Lupus

AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease in which outcomes vary among different racial groups. We leverage cell-sorted RNA-seq data (CD14+ monocytes, B cells, CD4+ T cells, and NK cells) from 120 SLE patients (63 Asian and 57 White individuals) and apply a four-tier approach including unsupervised clustering, differential expression analyses, gene co-expression analyses, and machine learning to identify SLE subgroups within this multiethnic cohort. K-means clustering on each cell-type resulted in three clusters for CD4 and CD14, and two for B and NK cells. To understand the identified clusters, correlation analysis revealed significant positive associations between the clusters and clinical parameters including disease activity as well as ethnicity. We then explored differentially expressed genes between Asian and White groups for each cell-type. The shared differentially expressed genes across cells were involved in SLE or other autoimmune-related pathways. Co-expression analysis identified similarly regulated genes across samples and grouped these genes into modules. Finally, random forest classification of disease activity in the White and Asian cohorts showed the best classification in CD4+ T cells in White individuals. The results from these analyses will help stratify patients based on their gene expression signatures to enable SLE precision medicine.

scholarly journals Novel expression signatures identified by transcriptional analysis of separated leucocyte subsets in systemic lupus erythematosus and vasculitis

2009 ◽  
Vol 69 (6) ◽  
pp. 1208-1213 ◽  
Author(s):  
Paul A Lyons ◽  
Eoin F McKinney ◽  
Tim F Rayner ◽  
Alexander Hatton ◽  
Hayley B Woffendin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Differentially Expressed Genes ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Differentially Expressed ◽  
Transcriptional Analysis ◽  
Expression Data ◽  
Systemic Lupus ◽  
Disease Pathogenesis

ObjectiveTo optimise a strategy for identifying gene expression signatures differentiating systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis that provide insight into disease pathogenesis and identify biomarkers.Methods44 vasculitis patients, 13 SLE patients and 25 age and sex-matched controls were enrolled. CD4 and CD8 T cells, B cells, monocytes and neutrophils were isolated from each patient and, together with unseparated peripheral blood mononuclear cells (PBMC), were hybridised to spotted oligonucleotide microarrays.ResultsUsing expression data obtained from purified cells a substantial number of differentially expressed genes were identified that were not detectable in the analysis of PBMC. Analysis of purified T cells identified a SLE-associated, CD4 T-cell signature consistent with type 1 interferon signalling driving the generation and survival of tissue homing T cells and thereby contributing to disease pathogenesis. Moreover, hierarchical clustering using expression data from purified monocytes provided significantly improved discrimination between the patient groups than that obtained using PBMC data, presumably because the differentially expressed genes reflect genuine differences in processes underlying disease pathogenesis.ConclusionAnalysis of leucocyte subsets enabled the identification of gene signatures of both pathogenic relevance and with better disease discrimination than those identified in PBMC. This approach thus provides substantial advantages in the search for diagnostic and prognostic biomarkers in autoimmune disease.

scholarly journals THU0221 EVIDENCE FOR A PATHOGENIC ROLE OF EXTRA-FOLLICULAR, IL-10 PRODUCING CCR6+B-HELPER T-CELLS IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 337-337
Author(s):  
M. Gerosa ◽  
F. Facciotti ◽  
P. Larghi ◽  
R. Bosotti ◽  
C. Vasco ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Helper T Cells ◽  
Systemic Lupus ◽  
Pathogenic Role

Background:IL-10 plays a key role in systemic lupus erythematosus (SLE) pathogenesis, promoting B-cell response. IL10 is mainly secreted by regulatory T-cells, but follicular helper T-cells (TFH), also produce it. We previously identified a subset of CCR6+IL-7R+T-cells in human tonsils providing IL-10-dependent B-cell help. These CCR6+T-cells were able to produce IL-10, inducing IgG production.Objectives:to investigate a possible role of CD4+CCR6+IL7R+T-cells in SLE pathogenesis.Methods:37 patients fulfilling the ACR criteria for SLE have been included. Disease activity was assessed by 2k-SLEDAI. PBMC were analyzed by flow cytometry, using specific lineage markers. CCR6+IL7R+T-cells purified from total PBMC of SLE patients or healthy donors (HD) were co-cultured with autologous CD20+B-cells. IL-10, Il-17, total IgG and anti-dsDNA antibodies titers in patients serum and culture supernatants were assessed by ELISA. Embedded sections of lymph nodes from 8 SLE patients were analyzed by immunofluorescence (IF).Results:IL10 levels were significantly higher in SLE patients (Fig 1A). CD4+CCR6+IL7R+T-cells were significantly increased in SLE, in particular in those with higher disease activity and higher IL10 levels. CD4+CCR6+IL7R+T-cells levels associated with anti-dsDNA positivity. CCR6+IL7R+T-cells of SLE patients induced production of IgG and anti-dsDNA IgG (in anti-dsDNA + patients) from autologous B-cells, providing spontaneous help for autoantibody productionex vivo(Fig 1B-C). The IF study of lymph nodes of SLE patients showed that IL-10-producing CCR6+T-cells were highly abundant and co-localized with B-cells at follicle margins.Fig 1Conclusion:our study revealed a novel population of extra-follicular B-helper T-cells, which produce IL-10 and could play a prominent pathogenic role in SLE. Further studies will clarify if this potentially pathogenic cell population might represent a possible future therapeutic target.References:[1]Facciotti F. J Allergy Clin Immunol. 2016; Geginat J. Semin Immunol. 2019; Tsokos GC. Nat Rev Rheumatol. 2019Tab 1:SLE patients characteristics(n=37)DemographicsFemale/Male, n37/5Age, years, median (IQR)44 (38-49)Disease duration, years, median (IQR)19 (11-26)Lab testsANA86%*anti-dsDNA (%)46% medium/high titre41%Disease activity and clinical manifestations SLEDAI-2K, median (min-max)3.5 (0-24) Moderate/high activity19%Ongoing therapyPrednisone dose mg/day, median (IQR)7,5 mg (2,5 – 20)hydroxychloroquine78%Immunosuppressants87%Fig 2Disclosure of Interests: :Maria Gerosa: None declared, Federica Facciotti: None declared, Paola Larghi: None declared, Roberto Bosotti: None declared, Chiara Vasco: None declared, Nicola Gagliani: None declared, Chiara Cordiglieri: None declared, Elsa Rottoli: None declared, Alessandra Emiliana Penatti: None declared, Lorenza Maria Argolini: None declared, Bhavna Karnani: None declared, Yasushi Kobayashi: None declared, Mauro Bombaci: None declared, Jan Piet Van Hamburg: None declared, Roberta Gualtierotti: None declared, Stefano Gatti: None declared, Sara Torretta: None declared, Lorenzo Pignataro: None declared, Sander W. Tas: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Sergio Abrignani: None declared, Massimiliano Pagani: None declared, Fabio Grassi: None declared, Pier Luigi Meroni: None declared, Richard Flavell: None declared, Jens Geginat: None declared

scholarly journals Methyl donor micronutrients, CD40-ligand methylation and disease activity in systemic lupus erythematosus: A cross-sectional association study

Lupus ◽  
2021 ◽  
pp. 096120332110345
Author(s):  
Stefan Vordenbäumen ◽  
Alexander Sokolowski ◽  
Anna Rosenbaum ◽  
Claudia Gebhard ◽  
Johanna Raithel ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Methylation ◽  
T Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cd40 Ligand ◽  
Systemic Lupus ◽  
Methyl Donors ◽  
Methyl Donor ◽  
The Mean

Objective Hypomethylation of CD40-ligand (CD40L) in T-cells is associated with increased disease activity in systemic lupus erythematosus (SLE). We therefore investigated possible associations of dietary methyl donors and products with CD40L methylation status in SLE. Methods Food frequency questionnaires were employed to calculate methyl donor micronutrients in 61 female SLE patients (age 45.7 ± 12.0 years, disease duration 16.2 ± 8.4 years) and compared to methylation levels of previously identified key DNA methylation sites (CpG17 and CpG22) within CD40L promotor of T-cells using quantitative DNA methylation analysis on the EpiTYPER mass spectrometry platform. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Linear regression modelling was used. P values were adjusted according to Benjamini & Hochberg. Results Amongst the micronutrients assessed (g per day), methionine and cysteine were associated with methylation of CpG17 (β = 5.0 (95%CI: 0.6-9.4), p = 0.04; and β = 2.4 (0.6-4.1), p = 0.02, respectively). Methionine, choline, and cysteine were additionally associated with the mean methylation of the entire CD40L (β = 9.5 (1.0-18.0), p = 0.04; β = 1.6 (0.4-3.0), p = 0.04; and β = 4.3 (0.9-7.7), p = 0.02, respectively). Associations of the SLEDAI with hypomethylation were confirmed for CpG17 (β=-32.6 (-60.6 to -4.6), p = 0.04) and CpG22 (β=-38.3 (-61.2 to -15.4), p = 0.004), but not the mean methylation of CD40L. Dietary products with the highest impact on methylation included meat, ice cream, white bread, and cooked potatoes. Conclusions Dietary methyl donors may influence DNA methylation levels and thereby disease activity in SLE.

scholarly journals OP0005 ELEVATED STAT1 EXPRESSION BUT NOT PHOSPHORYLATION IN LUPUS B CELLS CORRELATES WITH DISEASE ACTIVITY AND INCREASED PLASMABLAST SUSCEPTIBILITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 4-5
Author(s):  
A. Aue ◽  
F. Szelinski ◽  
S. Weißenberg ◽  
A. Wiedemann ◽  
T. Rose ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
B Cell Subsets

Background:Systemic lupus erythematosus (SLE) is characterized by two pathogenic key signatures, type I interferon (IFN) (1.) and B-cell abnormalities (2.). How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT).Objectives:JAK-STAT inhibition is an attractive therapeutic possibility for SLE (3.). We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared to other autoimmune diseases and healthy controls (HD) and related it to disease activity.Methods:Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T-cells of 21 HD, 10 rheumatoid arthritis (RA), 7 primary Sjögren’s (pSS) and 22 SLE patients was analyzed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs of SLE patients and HD after IFNα and IFNγ incubation were further investigated.Results:SLE patients showed substantially higher STAT1 but not pSTAT1 in B and T-cell subsets. Increased STAT1 expression in B cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker (4.). STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ.Figure 1.Significantly increased expression of STAT1 by SLE B cells(A) Representative histograms of baseline expression of STAT1, pSTAT1, STAT3 and pSTAT3 in CD19+ B cells of SLE patients (orange), HD (black) and isotype controls (grey). (B) Baseline expression of STAT1 and pSTAT1 or (C) STAT3 and pSTAT3 in CD20+CD27-, CD20+CD27+ and CD20lowCD27high B-lineage cells from SLE (orange) patients compared to those from HD (black). Mann Whitney test; ****p≤0.0001.Figure 2.Correlation of STAT1 expression by SLE B cells correlates with type I IFN signature (Siglec-1, CD169) and clinical activity (SLEDAI).Correlation of STAT1 expression in CD20+CD27- näive (p<0.0001, r=0.8766), CD20+CD27+ memory (p<0.0001, r=0.8556) and CD20lowCD27high (p<0.0001, r=0.9396) B cells from SLE patients with (A) Siglec-1 (CD169) expression on CD14+ cells as parameter of type I IFN signature and (B) lupus disease activity (SLEDAI score). Spearman rank coefficient (r) was calculated to identify correlations between these parameters. *p≤0.05, **p≤0.01. (C) STAT1 expression in B cell subsets of a previously undiagnosed, active SLE patient who was subsequently treated with two dosages of prednisolone and reanalyzed.Conclusion:Enhanced expression of STAT1 by B-cells candidates as key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold promise to block STAT1 expression and control plasmablast induction in SLE.References:[1]Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610-5.[2]Lino AC, Dorner T, Bar-Or A, Fillatreau S. Cytokine-producing B cells: a translational view on their roles in human and mouse autoimmune diseases. Immunol Rev. 2016;269(1):130-44.[3]Dorner T, Lipsky PE. Beyond pan-B-cell-directed therapy - new avenues and insights into the pathogenesis of SLE. Nat Rev Rheumatol. 2016;12(11):645-57.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, et al. Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum. 2008;58(4):1136-45.Disclosure of Interests:Arman Aue: None declared, Franziska Szelinski: None declared, Sarah Weißenberg: None declared, Annika Wiedemann: None declared, Thomas Rose: None declared, Andreia Lino: None declared, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen

scholarly journals THU0035 OX40L EXPRESSING NEUTROPHILS INDUCE CD4 T FOLLICULAR AND PERIPHERAL HELPER CELL DIFFERENTIATION IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 230.2-231
Author(s):  
A. Pappalardo ◽  
E. Wojciechowski ◽  
I. Odriozola ◽  
I. Douchet ◽  
N. Merillon ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Cd4 T Cells ◽  
Close Contact ◽  
Memory B Cells ◽  
Systemic Lupus ◽  
Research Support

Background:Neutrophils have been described as potent antigen-presenting cells able to activate T cells by MHC/TCR interaction and costimulatory molecules in tumor immunity. However, little is known about the direct interaction between neutrophils and CD4 T cells with respect to systemic lupus erythematosus (SLE). We have previously shown that OX40L expressed by monocytes from SLE patients promote the differentiation of naïve and memory cells into IL21 secreting T cells that are able to help B cells1,2.Objectives:In this study, we investigate OX40L expression on neutrophils from SLE patients and contribution of these OX40L+neutrophils in SLE pathogenesis to modulation of the B cell helper role of CD4 T cells.Methods:Surface expression of co-stimulatory molecules (OX40L, ICOSL, GITRL, 4-1BBL) on neutrophils from SLE patients and healthy donors (HD) was measured by flow cytometry (FC). Neutrophils from HD were stimulated with TLR7 or TLR8 agonists and IFNα after 5 hours of culture, OX40L expression was measured by FC and Western Blotting. CD4 T cells were cultured with the stimulated neutrophils for 3 days. At the end of the co-culture, percentages of IL21-expressing T follicular (Tfh) and peripheral helper (Tph) cells measured by FC. These generated T cells were also cultured in the presence of memory B cells. After 5 days of co-culture, plasmablast generation and Ig levels were assessed by FC and ELISA, respectively. Inhibition of OX40-OX40L interaction in vitro was achieved using ISB 830, a novel anti-OX40 mAb currently used in clinical trials.Results:Among the co-stimulatory molecules tested, percentages of OX40L+neutrophils in SLE (n=54) were increased compared to HD (n=25)(mean + SD: HD = 1,34%±1.62 vs SLE = 4,53%±8.1; p=0.29). OX40L expression positively correlated with SLE disease activity score (SLEDAI) (p = 0,04; r = 0,31) and with anti-DNA antibodies (p= 0,04, r = 0,33). Of note, the percentage of OX40L+neutrophils was higher in anti-sm-RNP+patients (n=16, mean= 9%±9.8), compared to anti-sm-RNP-patients (n=27, mean = 1,4%±2.5; p = 0,02). The percentage of OX40L+neutrophils was higher in patients with class III or IV lupus nephritis, and inflammatory infiltrate within the kidney biopsy disclosed OX40L+neutrophils, in close contact with T cells. Neutrophils from HD express OX40L with TLR8 agonist, or IFNα priming followed by TLR7 agonist. When memory CD4 T cells were cultured in the presence of TLR8-stimulated neutrophils, the proportion of IL21-expressing Tfh (CXCR5+PD1+) and Tph (CXCR5-PD1hi) were increased, compared to culture with unstimulated neutrophils. This process was dependent on OX40-OX40L interactions, since in vitro treatment with the anti-OX40 blocking antibody ISB 830, inhibited the differentiation of memory T cells into Tfh and Tph. Both generated Tfh and Tph were able to promote the differentiation of memory B cells into Ig-secreting plasmablasts.Conclusion:Our results disclose an unprecedented phenomenon where cross-talk between TLR7/8-activated neutrophils and CD4 lymphocytes operates through OX40L-OX40 costimulation, and neutrophils promote the differentiation of pro-inflammatory Tfh and Tph, as well as IL21 production. Therefore, OX40L/OX40 should be considered as a potentially therapeutic axis in SLE patients.References:[1]Jacquemin et al. Immunity 2015;[2]Jacquemin et al. JCI Insight 2018Disclosure of Interests:Angela Pappalardo Grant/research support from: Ichnos Sciences, Elodie Wojciechowski: None declared, Itsaso Odriozola: None declared, Isabelle Douchet: None declared, Nathalie Merillon: None declared, Andrea Boizard-Moracchini: None declared, Pierre Duffau: None declared, Estibaliz Lazaro: None declared, Marie-Agnes Doucey Employee of: Ichnos Sciences, Lamine Mbow Employee of: Ichnos Sciences, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Patrick Blanco Grant/research support from: Ichnos Sciences

scholarly journals The expansion of activated naive DNA autoreactive B cells and its association with disease activity in systemic lupus erythematosus patients

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Kittikorn Wangriatisak ◽  
Chokchai Thanadetsuntorn ◽  
Thamonwan Krittayapoositpot ◽  
Chaniya Leepiyasakulchai ◽  
Thanitta Suangtamai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoreactive B Cells ◽  
Dsdna Antibody ◽  
Cell Subpopulations ◽  
B Cell Subsets

Abstract Background Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. Methods Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients’ peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. Results The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. Conclusion Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.

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