Cellular and molecular determinants mediating the dysregulated germinal center immune dynamics in systemic lupus erythematosus

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 13, 2025

Systemic lupus erythematosus (SLE) is characterized by dysregulated humoral immunity, leading to the generation of autoreactive B cells that can differentiate both within and outside lymph node (LN) follicles. Here, we employed spatial transcriptomics multiplex imaging investigate follicular immune landscaping in situ transcriptomic profile LNs from SLE individuals. Our analysis revealed robust type I IFN plasma cell signatures compared reactive, control Cell deconvolution T subsets are mainly affected fingerprint Dysregulation TFH differentiation was documented i) significant reduction Bcl6hi cells, ii) reduced density potential IL-4 producing associated with impaired signature signaling iii) loss their correlation GC-B cells. This accompanied a marked an enrichment extrafollicular CD19hiCD11chiTbethi, age-associated (ABCs), known for potential. The increased prevalence IL-21hi further reveals hyperactive microenvironment control. Taken together, our findings highlight altered immunological landscape follicles, likely fueled potent inflammatory signals such as sustained and/or IL-21 signaling. work provides novel insights into molecular cellular dynamics, points druggable targets restore tolerance enhance vaccine responses patients.

Language: Английский

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Immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus

Lupus, Journal Year: 2024, Volume and Issue: 33(5), P. 450 - 461

Published: Feb. 9, 2024

Objectives We evaluated the immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus (adoSLE) receiving either high- or low-dose immunosuppressant (High-IS Low-IS). Methods Patients aged 12–18 years diagnosed SLE were enrolled. High-IS was defined as >7.5 mg/day prednisolone other immunosuppressant, while Low-IS only ≤7.5 no immunosuppressant. Two doses given 4 weeks apart, followed by a booster (third) dose at 4–6 months later. Anti-spike receptor binding domain (anti-RBD) IgG against Wuhan, neutralising antibody (NT) Wuhan Omicron variants, cellular immune response IFN-γ-ELISpot assay following vaccination. Adverse events (AEs) flare monitored. Results A total 73 participants enrolled, 40 33 group, respectively. At 2nd dose, overall anti-RBD seropositivity 97.3%, difference between groups ( p = .498). AdoSLE on had lower < .001), NT .022) than those Low-IS. 3rd induced significantly higher responses after .001) both established seroconversion persistent levels group. SELENA-SLEDAI scores within 12 2-dose before (3.1 vs 2.5; .036); however, occurrence disease index not different compared to vaccination, consistent across groups. Non-severe AEs occurred similarly Conclusion SARS-CoV-2 vaccine Vaccination can increase activity requires close monitoring for flare.

Language: Английский

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Systemic Lupus Erythematosus and COVID-19

Current Rheumatology Reports, Journal Year: 2023, Volume and Issue: 25(10), P. 192 - 203

Published: July 21, 2023

To describe the current state of knowledge regarding COVID-19 in patients with systemic lupus erythematosus (SLE). We focus on (i) SARS-CoV-2 vaccination uptake, immunogenicity and safety, (ii) outcomes SLE pertinent risk factors for adverse sequelae. Notwithstanding potential concern about possible post-vaccination side-effects, safety anti-SARS-CoV-2 vaccines has been undisputedly confirmed numerous studies. Humoral is generally attained SLE, although affected by use background immunosuppressive drugs, especially rituximab. The latter also clearly implicated including need hospitalization, mechanical ventilation death. Although wide adoption significantly improved outcomes, continue to pose challenges during pandemic, mainly owing administered medications.

Language: Английский

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Risk of disease flares after SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus

Immunological Medicine, Journal Year: 2024, Volume and Issue: 47(2), P. 76 - 84

Published: Jan. 8, 2024

This study aims to elucidate the effectiveness and safety of SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus (SLE). We enrolled uninfected SLE who received two vaccine doses (BNT162b2 or mRNA-1273) historical unvaccinated patients. Neutralizing antibodies, adverse reactions, disease flares were evaluated 4 weeks after second vaccination. Ninety each group. Among vaccinated patients, Disease Activity Index (SLEDAI), prednisolone before 2, 5 mg/d, respectively. After vaccination, 19 (21.1%) had no neutralizing antibodies. Adverse reactions occurred 88.9% within 3 d. Negative antibodies associated anemia mycophenolate mofetil administration. SLEDAI increased modestly but significantly 13 (14.4%) experiencing (4.4%) severe (nephritis three vasculitis one). The flare rate was higher than controls. mean duration between 35 d, at least 8 days Multivariable analysis showed that high anti-dsDNA flares. type, antibody titer, reaction frequency did not affect Therefore, residual activity increases risk.

Language: Английский

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Uptake, effectiveness and safety of COVID-19 vaccines in individuals at clinical risk due to immunosuppressive drug therapy or transplantation procedures: a population-based cohort study in England

BMC Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 10, 2024

Language: Английский

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Predictors of a weak antibody response to COVID-19 mRNA vaccine in systemic lupus erythematosus

Rheumatology International, Journal Year: 2023, Volume and Issue: 43(9), P. 1621 - 1627

Published: June 13, 2023

Language: Английский

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Vaccination updates and special considerations for systemic lupus erythematosus patients

Current Opinion in Rheumatology, Journal Year: 2023, Volume and Issue: 36(2), P. 148 - 153

Published: Nov. 16, 2023

Purpose of review We the latest guidelines and note special considerations for systemic lupus erythematosus (SLE) patients when approaching vaccination against SARS-CoV-2, influenza, pneumococcus, herpes zoster, potentially respiratory syncytial virus (RSV) vaccine in future. Recent findings SLE have unique infectious risks due to newer treatments nature disease itself. It is important balance benefit additional protective immunity from updated vaccines possible risk activity exacerbations. Summary continuously evaluate safety immunogenicity specifically patients. Additionally, newly approved RSV should be considered this population reduce severe illness.

Language: Английский

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Reply

Arthritis Care & Research, Journal Year: 2023, Volume and Issue: 75(10), P. 2225 - 2225

Published: March 2, 2023

In our study (1), we excluded both health care workers and patients with systemic lupus erythematosus who had a history of COVID-19 infection so the observed antibody levels could be attributed to vaccinations. We agree implicit point that small number unrecognized might have been included in groups. Asymptomatic has reported immunocompromised individuals autoimmune diseases (2), but comprehensive studies are lacking. The frequency asymptomatic infections among those screened for was very low one study, 0.25% (3). observational limitations. However, see no reason why would biased findings regarding relative between two addition, this not affected any within-lupus analyses results. Disclosure Form Please note: publisher is responsible content or functionality supporting information supplied by authors. Any queries (other than missing content) should directed corresponding author article.

Language: Английский

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The outcome of COVID‐19 in patients with autoimmune rheumatic diseases: Comparable to the general population or worse?

International Journal of Rheumatic Diseases, Journal Year: 2023, Volume and Issue: 26(8), P. 1435 - 1439

Published: Aug. 1, 2023

Since the beginning of COVID-19 pandemic, patients with autoimmune rheumatic diseases (AIRDs) have been a focus concern due to underlying immune dysregulation and immunosuppressive drugs they are receiving. The data regarding total effect AIRDs their treatment on course outcome currently inconclusive. Also, it is challenging, if not impossible, dissect impact from other comorbidities. Several factors associated could affect (Table 1). Severe complications generally caused by hyperinflammatory response against SARS-CoV-2. Thus, dysregulated system tendency overreact make AIRD more prone negative outcomes. type AIRD, disease activity, organ involvements also important while analyzing course.1, 2 In addition, classical comorbidities such as hypertension, obesity, diabetes mellitus frequent among than general population, these worse outcomes.3, 4 On hand, most chronic therapies, which may limit hyperinflammation before cytokine storm commences. But also, lead an increased risk for SARS-CoV-2 itself rather host's system. Regarding treatment, duration therapy, drugs, dose glucocorticoids that differently course.4-7 Lastly, vaccines be less efficient in or dysregulation.7, 8 This contribute severe despite vaccination. Another aspect about pandemic's effects care pandemic has interruptions routine follow-up patients. Although telemedicine tools increasingly used clinical practice, efficacy limited compared in-person visits. George et al9 showed stopping immunomodulatory was likely followed up visits those office These adequate control during after infections. effective collaboration between internist who treats rheumatologist utmost importance improving both AIRDs. Severely active renal, cardiovascular, pulmonary involvement Disease-specific outcomes (such erosive arthritis seropositivity rheumatoid arthritis). efficiency vaccine decrease. Patients complications. Generally Some anti-TNF agents) decreased hospitalization rate. Chronic decrease response. therapeutics COVID-19. Recently, Abdulnaby al10 66 64 without They failed show significant differences two groups severity. However, observed higher frequency septic shock patients, longer recovery glucocorticoids, hypertension COVID-19.10 parameters seem similar, there were several features. For instance, male gender smoking studies, significantly group lung common group. coming might balanced point until (10.5 days vs. 6 days; P < 0.001). differed groups. Around 40% (n = 27; 42.2%) received tocilizumab, only (6.3%) got tocilizumab Tocilizumab, strong anti-inflammatory biologic drug, till Furthermore, use had possibly affected laboratory test results different (i.e., ferritin, D-dimer, C-reactive protein patients). reason difference controls rate concomitant therapy. already certain treated concerns agents. Septic 7 whole cohort. this result should evaluated carefully considering polymerase chain reaction performed around 1/4 Moreover, pre-COVID-19 glucocorticoid activity complication. authors receiving except It interesting see ≥10 mg/d prednisone equivalent lower doses glucocorticoids. Having studies.11-14 obesity cardiovascular diseases. And difficult conclude comes directly disease. systematic review meta-analysis, Akiyama al5 analyzed 62 observational including 319 025 diseases, demonstrated slightly prevalence population. investigated meta-analysis 65 studies included 2766 Among highest mortality rates. essential mention elderly comorbidities.5 using conventional synthetic disease-modifying anti-rheumatic (csDMARDs), combination therapies DMARDs outcomes.5 Global Rheumatology Alliance Physician Reported Registry, Strangfeld al4 COVID-19-related disease-specific moderate-high specific sulfasalazine rituximab, along known (male gender, older age, comorbidities). Rorat al15 recently 185 8035 pulmonary, kidney mixed cohorts included. makes challenging analyze individual course. number focusing increasing. Bruera al1 reported systemic lupus erythematosus (SLE) controls, even adjustments finding suggests at least partially SLE. mycophenolate mofetil, tacrolimus SLE related worth mentioning usually receive intensive so Raiker al16 2135 propensity score matched controls. unit (ICU) admission, mechanic ventilation, all-cause although rates comparable groups.16 nationwide cross-sectional study 125 119 Bertoglio al17 (adjusted comorbidities) all hospitalized acute respiratory distress syndrome. Rheumatoid (RA) large cohort England al18 (33 886 RA 33 non-RA controls). Figueroa-Parra al19 582 versus 2875 especially (anticyclic citrullinated peptide factor positivity), interstitial disease, bone erosions risk.19 Cordtz al20 similarly depicted vaccination Danish study, 28 447 568 940 There types Bournia al21 RA, ankylosing spondylitis (AS), psoriatic (PsA), SLE, sclerosis (SSc), SSc, Chevalier al22 1213 AIRD. As types, sarcoidosis, vasculitis, autoinflammatory multivariate analysis. suggest introduce levels some features COVID-19-associated Behçet's antiphospholipid syndrome (APLS) thrombosis cause thrombotic Interestingly, did differ APLS population previous studies.23-25 AIRDs, (prednisone equivalent), csDMARDs sulfasalazine, immunosuppressant mofetil tacrolimus, B cell depleting rituximab belimumab, Janus kinase (JAK) inhibitors main 4, 6, 26 suggested anti-tumor necrosis outcome.5, 26-29 conflicting 687 6870 methotrexate, leflunomide, cyclosporine, tacrolimus; but azathioprine, cyclophosphamide, rituximab. belimumab protective COVID-19.1 contrast, Singh al30 conferred 3–5 fold odds admission ventilation national 69 549 comorbidities, single drug outcome. risks caution risk. Vaccination substantially changed infection Most recently, Kharouf al3 outbreaks campaigns. AIRD-related involvement, mellitus, JAK And, renal vascular congestive heart failure, mortality. outbreak delta variant outbreaks. stated campaigns probably difference. Along same lines Kawano al31 proportion since early recent periods. emphasized vaccination, advances diagnosis management An consideration exert stemming treatment. keeps policies. Hoff al,8 breakthrough infections Petri al7 shown immunoglobulin G (IgG) regardless background reduced IgG area debate. Qian al outpatient therapy anti-viral monoclonal anti-SARS-CoV-2 antibodies patients.32 According published points consider European Reference Network Rare Complex Connective Tissue Musculoskeletal Diseases (ERN ReCONNET), anti-virals can considered mild moderate COVID-19.33 conclusion, depending presence Considering and/or anti-SARS-CoV2 improve Batu ED wrote first draft manuscript. Erden A critically revised text. Both read approved final None. work any grant funding agencies public, commercial, not-for-profit sectors. declare no conflicts interest. confirm supporting findings available within article.

Language: Английский

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Does the use of corticosteroids and immunosuppressants increase the risk of COVID-19 infection among people with systemic lupus erythematosus?

Lupus Science & Medicine, Journal Year: 2023, Volume and Issue: 10(2), P. e000961 - e000961

Published: Oct. 1, 2023

An important clinical question is whether the use of immunosuppressants or corticosteroids increases risk incident COVID-19 disease among patients with SLE. To address this question, we examined incidence infection in a large SLE cohort.

Language: Английский

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