scholarly journals OP0049 EFFICACY OF ANIFROLUMAB IN ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: PATIENT SUBGROUP ANALYSIS OF BICLA RESPONSE IN 2 PHASE 3 TRIALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 32-32
Author(s):  
E. F. Morand ◽  
R. Furie ◽  
Y. Tanaka ◽  
R. Kalyani ◽  
G. Abreu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age At Onset ◽  
Standard Of Care ◽  
Response Rates ◽  
Type I ◽  
Systemic Lupus ◽  
Research Support ◽  
Phase 3 ◽  
Organ Systems

Background:Treatment of patients with systemic lupus erythematosus (SLE) with the type I interferon (IFN) receptor inhibitor anifrolumab resulted in higher British Isles Lupus Assessment Group (BILAG)–based Composite Lupus Assessment (BICLA) response rates vs placebo at Week 52 in the phase 3 randomized trials, TULIP-2 (primary endpoint; 16.3% difference)1and TULIP-1 (secondary endpoint; 16.4% difference).2BICLA is a validated composite global disease measure that registers both partial and complete improvement within organ systems.Objectives:TULIP-2 and TULIP-1 data were analyzed to evaluate BICLA responses to anifrolumab vs placebo at Week 52 in protocol-defined subgroups of patients with active SLE.Methods:TULIP-2 and TULIP-1 were randomized, double-blind, placebo-controlled trials that evaluated efficacy and safety of intravenous anifrolumab vs placebo administered every 4 weeks, with the primary endpoints assessed at Week 52, in patients with moderate to severe SLE despite standard-of-care treatment.1,2BICLA responses are defined by all of the following: reduction of baseline BILAG-2004 A and B domain scores to B/C/D and C/D, respectively, and no worsening in any organ system; no worsening of the SLE Disease Activity Index 2000 (SLEDAI-2K) score; no worsening of ≥0.3 points in the Physician’s Global Assessment (range 0–3); no trial treatment discontinuation; and no use of medications restricted by the protocol.3BICLA responses were compared between anifrolumab 300 mg and placebo groups, and robustness of BICLA responses was assessed across protocol-defined subgroups. TULIP-1 data were analyzed incorporating the amended restricted medication rules, as described.2Results:In TULIP-2 and TULIP-1, 180 patients in each trial received anifrolumab 300 mg (182 and 184 patients received placebo, respectively). Baseline demographics, disease characteristics, and standard-of-care medications were balanced between anifrolumab and placebo groups within both TULIP trials. Patients in TULIP-2 and TULIP-1 had comparable BICLA responses (Figure). Across multiple subgroups, higher percentages of patients achieved BICLA responses at Week 52 in the anifrolumab vs placebo arms (Figure). There was concordance of BICLA responses favoring anifrolumab across the protocol-defined subgroups of baseline disease severity (SLEDAI-2K <10 points [difference 15.3%, TULIP-2; 16.9%, TULIP-1] vs ≥10 points [difference 16.7%, TULIP-2; 17.1%, TULIP-1]) and baseline oral corticosteroid use (prednisone or equivalent <10 mg/d [difference 20.1%, TULIP-2; 16.2%, TULIP-1] vs ≥10 mg/d [difference 12.0%, TULIP-2; 17.7%, TULIP-1]). Numerically different BICLA effect sizes between the anifrolumab vs placebo arms were observed in both studies in relation to baseline IFN gene signature status (high [difference 17.3%, TULIP-2; 19.1%, TULIP-1] vs low [difference 11.2%, TULIP-2; 7.5%, TULIP-1]). Other subgroups including age, sex, age at onset, race, and anti-drug antibody status showed similar uniformity of response.Conclusion:The uniformity of robust BICLA response rates across prespecified subgroups in both phase 3 trials shows consistent clinical benefit of anifrolumab irrespective of patient baseline characteristics. However, given the small patient numbers in some subgroups, these results should be interpreted with caution.References:[1]Morand EF, et al.N Engl J Med.2020;382:211–221.[2]Furie RA, et al.Lancet Rheumatol. 2019;1:e208–e219.[3]Wallace DJ, et al.Ann Rheum Dis.2014;73:183–190.Disclosure of Interests:Eric F. Morand Grant/research support from: AstraZeneca, Consultant of: AstraZeneca, Speakers bureau: AstraZeneca, Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Rubana Kalyani Employee of: AstraZeneca, Gabriel Abreu Employee of: AstraZeneca, Lilia Pineda Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca

scholarly journals SAT0182 THE ASSOCIATION BETWEEN AUTOANTIBODIES AND RITUXIMAB RESPONSE IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1032.2-1032
Author(s):  
D. Li ◽  
H. Lu ◽  
J. Dunphy ◽  
T. Smith ◽  
E. Vital ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Systemic Lupus ◽  
Research Support ◽  
Chi Square ◽  
System Involvement ◽  
Organ Systems ◽  
Chi Square Analysis

Background:Systemic Lupus Erythematosus (SLE) is clinically and immunologically heterogeneous with a variable response to treatment. MASTERPLANS is an MRC-funded consortium that seeks to identify immunophenotypic subgroups of patients that predict response to therapy. Autoantibody profiles can differentiate subgroups of patients and have potential to predict response to treatment.Objectives:To determine whether known and novel autoantibodies are associated with response to rituximab (RTX), and analyse the association between these antibodies and disease involvement in various organ systems.Methods:Serum was obtained from 224 SLE patients in the BILAG Biologics Registry who received rituximab according to NHS England criteria (2). Patients were recruited if they were starting a first cycle of rituximab for active SLE (BILAG A or 2xBILAG B) despite previous cyclophosphamide or mycophenolate mofetil. Evidence of any single organ system involvement previous or current was taken as having a BILAG score of A-D but not E. Disease activity was measured using BILAG-2004. Clinical response was defined as improvement by >=1 grade in active BILAG-2004 systems with no worsening in other systems. Autoantibodies were measured by immunoprecipitation of proteins by sera from35S-labelled K562 cell lines, followed by SDS-PAGE separation and autoradiography. Autoantibodies not able to be detected by this technique (anti-Ro52, anti-dsDNA and aCL) were measured by ELISA. Autoantibody data was analysed in IBM SPSS and GraphPad Prism v8.2. Association between autoantibodies and RTX response was analysed using binary logistic interaction terms and Pearson’s Chi-Square test.Results:Of the 224 patients (201 female, 23 male, median age 40 years) the most common system involvement from the 9 BILAG domains was musculoskeletal (164 patients) and the least ophthalmic (11 patients). Patients with anti-Ro52 and anti-U1RNP/Sm had more frequent involvement of mucocutaneous (p<0.036,p<0.012) and musculoskeletal domains (p<0.015 for U1RNP) respectively.There were 136 patients with sufficient data to define as either responders (n=67) or non-responders (n=69) to RTX at 6 months. RTX responders had a higher frequency of anti-U1RNP/Sm compared to non-responders (Figure 1). Further Pearson’s Chi-Square analysis showed a significant association between presence of anti-U1RNP/Sm and better response to RTX (p<0.018).Conclusion:Our findings suggest that the presence of U1RNP/Sm autoantibodies in a cohort of patients who have received treatment with RTX is associated with more frequent musculoskeletal and mucocutaneous involvement and predicts a more favourable response to treatment.Acknowledgments :Funded by a grant from the Medical Research Council, grant number MR/M01665X/1. BILAG BR has been funded by unrestricted educational donations from Roche, GSK and LUPUS UK. Part-funded by a grant from LUPUS UK.Disclosure of Interests: :Danyang Li: None declared, Hui Lu: None declared, Juliet Dunphy: None declared, Theresa Smith: None declared, Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK, Ian N. Bruce Grant/research support from: Genzyme Sanofi, GSK, and UCB, Consultant of: Eli Lilly, AstraZeneca, UCB, Iltoo, and Merck Serono, Speakers bureau: UCB, Neil McHugh: None declared

scholarly journals SAT0174 FLARE ASSESSMENTS IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS TREATED WITH ANIFROLUMAB IN 2 PHASE 3 TRIALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1028.1-1029 ◽  
Author(s):  
R. Furie ◽  
E. F. Morand ◽  
A. Askanase ◽  
E. Vital ◽  
R. Kalyani ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Rate Ratio ◽  
Negative Binomial ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards Model ◽  
Negative Binomial Regression Model ◽  
Systemic Lupus ◽  
Research Support ◽  
Phase 3

Background:Anifrolumab treatment resulted in improved British Isles Lupus Assessment Group (BILAG)–based Composite Lupus Assessment (BICLA) response rates in patients with systemic lupus erythematosus (SLE) in the phase 3 TULIP-2 and TULIP-1 trials.1,2In addition, annualized flare rates were lower among the groups treated with anifrolumab compared with placebo.1,2Objectives:TULIP-2 and TULIP-1 data were analyzed to assess the effects of anifrolumab on the number of SLE flares and time to first flare during 52 weeks of treatment.Methods:The randomized, double-blind, placebo-controlled TULIP-2 and TULIP-1 trials evaluated efficacy and safety of intravenous anifrolumab 300 mg vs placebo every 4 weeks for 48 weeks, with the primary endpoints assessed at Week 52, in patients with moderate to severe SLE despite standard-of-care treatment. Flares were defined as ≥1 new BILAG-2004 A or ≥2 new (worsening) BILAG-2004 B domain scores compared with the prior month’s visit. Time to first flare was evaluated using a Cox proportional hazards model. Annualized flare rate was analyzed using a negative binomial regression model.Results:In TULIP-2 (anifrolumab, n=180; placebo, n=182) and TULIP-1 (anifrolumab, n=180; placebo, n=184), fewer patients experienced ≥1 BILAG-2004 flare in the anifrolumab groups (TULIP-2: 31.1%, n=56; TULIP-1: 36.1%, n=65) compared with the placebo groups (TULIP-2: 42.3%, n=77; TULIP-1: 43.5%, n=80; Figure 1). Results favoring anifrolumab were observed in time to first flare (TULIP-2: hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.46–0.91 and TULIP-1: HR 0.76, 95% CI 0.55–1.06; Figure 2) and BILAG-based annualized flare rates (TULIP-2: adjusted rate ratio 0.67, 95% CI 0.48–0.94 and TULIP-1: rate ratio 0.83, 95% CI 0.60–1.14) across both trials.Conclusion:Across 2 phase 3 trials, we observed reductions in the total number of flares and annualized flare rates, as well as prolongation of time to first flare with anifrolumab treatment compared with placebo. These results support the potential of anifrolumab to reduce disease activity and reduce flares, benefiting patients with SLE.References:[1]Morand EF, et al.N Engl J Med. 2020;382:211–221.[2]Furie RA, et al.Lancet Rheumatol.2019;1:e208–e219.Disclosure of Interests:Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Eric F. Morand Grant/research support from: AstraZeneca, Consultant of: AstraZeneca, Speakers bureau: AstraZeneca, Anca Askanase Grant/research support from: Regeneron and Pfizer, Consultant of: AbbVie and BMS, Employee of: GSK, AstraZeneca, Janssen, Lilly, and Mallinckrodt, Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK, Rubana Kalyani Employee of: AstraZeneca, Gabriel Abreu Employee of: AstraZeneca, Lilia Pineda Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca

THE CLINICAL, LABORATORY MANIFESTATIONS AND HISTOPATHOLOGY IN NEPHROTIC PATIENTS WITH LUPUS NEPHRITIS

2018 ◽  
pp. 52-58
Author(s):  
Le Thuan Nguyen ◽  
Bui Bao Hoang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Clinical Laboratory ◽  
Activity Index ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Organ Systems ◽  
Tubulointerstitial Lesions

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. The kidney appears to be the most commonly affected organ, especially nephrotic is a serious kidney injury. The clinical, laboratory manifestations and histopathology are very useful for diagnosis, provide the means of predicting prognosis and guiding therapy in nephrotic patients with lupus nephritis. Methods: Descriptive cross-sectional study of nephrotic patients with lupus treated in the Department of Nephrology Trung Vuong Hospital and Cho Ray Hospital between May/2014 and May/2017. Renal histopathological lesions were classified according to International Society of Nephrology/Renal Pathology Society - ISN/RPS ’s 2003. The clinical, laboratory manifestations and histopathological features were described. Results: Of 32 LN with nephritic range proteinuria cases studied, 93.7% were women. The 3 most common clinical manifestations were edema (93.8%), hypertension (96.8%) and pallor (68.9%), musculoskeletal manifestions (46.9%), malar rash (40.6%). There was significant rise in laboratory and immunological manifestions with hematuria (78.1%), Hb < 12g/dL (93.5%), increased Cholesterol (100%), and Triglycerid (87.5%), Creatinine > 1.4 mg/dL (87.5%), increased BUN 71.9%, ANA (+) 93.8%, Anti Ds DNA(+) 96.9%, low C3: 96.9%, low C4: 84.4%. The most various and severe features were noted in class IV with active tubulointerstitial lesions and high activity index. Conclusion: Lupus nephritis with nephrotic range proteinuria has the more severity of histopathological feature and the more severity of the more systemic organ involvements and laboratory disorders were noted. Key words: Systemic lupus, erythematosus (SLE) lupus nepphritis, clinical

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

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

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

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