Recommendations for physical activity and exercise in persons living with Systemic Lupus Erythematosus (SLE): consensus by an international task force.

OBJECTIVE: This international task force aimed to provide healthcare professionals and persons living with systemic lupus erythematosus (SLE) with consensus-based recommendations for physical activity and exercise in SLE. METHODS: Based on evidence from a systematic literature review and expert opinion, 3 overarching principles and 15 recommendations were agreed on by Delphi consensus. RESULTS: The overarching principles highlight the importance of shared decision-making and the need to explain the benefits of physical activity to persons living with SLE and other healthcare providers. The 15 specific recommendations state that physical activity is generally recommended for all people with SLE, but in some instances, a medical evaluation may be needed to rule out contraindications. Pertaining to outdoor activity, photoprotection is necessary. Both aerobic and resistance training programmes are recommended, with a gradual increase in frequency and intensity, which should be adapted for each individual, and ideally supervised by qualified professionals. CONCLUSION: In summary, the consensus reached by the international task force provides a valuable framework for the integration of physical activity and exercise into the management of SLE, offering a tailored evidence-based and eminence-based approach to enhance the well-being of individuals living with this challenging autoimmune condition.

High-density lipoprotein cholesterol subfraction HDL2 is associated with improved endothelial function in systemic lupus erythematosus.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have increased risk of premature atherosclerosis but the exact mechanisms remains unclear. Flow-mediated dilatation (FMD) is an established non-invasive assessment of vascular endothelial function. Lipoprotein subfractions may be better predictors of FMD than conventional cholesterol measurements. We tested the hypothesis that lipoprotein subfractions are independently associated with FMD. METHODS: Forty-one consecutive adult patients with SLE without known cardiovascular risk factors or disease were recruited in this cross-sectional study. Endothelial function and early atherosclerosis were assessed by brachial FMD and common carotid artery (CCA) intima-media thickness (IMT). High-density lipoprotein (HDL)/low-density lipoprotein (LDL) subfractions were measured. Machine learning models were also constructed to predict FMD and CCA IMT. RESULTS: Median FMD was 4.48% (IQR 5.00%) while median IMT was 0.54 mm (IQR 0.12 mm). Univariate analysis showed lower LDL1 (r=-0.313, p<0.05) and higher HDL2 subfractions (r=0.313, p<0.05) were significantly associated with higher log-transformed FMD. In a multiple linear regression model, HDL2 (ß=0.024, SE=0.012, p<0.05) remained an independent predictor of higher FMD after adjusting for age, body mass index, LDL1 and systolic blood pressure. The machine learning model included parameters such as HDL2 (positive association), prednisolone dose, LDL cholesterol and LDL1 for prediction of FMD (r=0.433, p<0.01). Age, LDL cholesterol and systolic blood pressure were independently associated with higher CCA IMT after adjusting for body mass index and HDL2. CONCLUSIONS: HDL 2, a large HDL particle, was independently associated with greater FMD and may be a biomarker of vascular health in SLE.

Combining multimodal magnetic resonance brain imaging and machine learning to unravel neurocognitive function in non-neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To study whether multimodal brain MRI comprising permeability and perfusion measures coupled with machine learning can predict neurocognitive function in young patients with SLE without neuropsychiatric manifestations. METHODS: SLE patients and healthy controls (HCs) (≤40 years of age) underwent multimodal structural brain MRI that comprised voxel-based morphometry (VBM), magnetization transfer ratio (MTR) and dynamic contrast-enhanced (DCE) MRI in this cross-sectional study. Neurocognitive function assessed by Automated Neuropsychological Assessment Metrics was reported as the total throughput score (TTS). Olfactory function was assessed. A machine learning-based model (i.e. glmnet) was constructed to predict TTS. RESULTS: Thirty SLE patients and 10 HCs were studied. Both groups had comparable VBM, MTR, olfactory bulb volume (OBV), olfactory function and TTS. While after correction for multiple comparisons the uncorrected increase in the blood-brain barrier (BBB) permeability parameters compared with HCs did not remain evident in SLE patients, DCE-MRI perfusion parameters, notably an increase in right amygdala perfusion, was positively correlated with TTS in SLE patients (r = 0.636, false discovery rate P < 0.05). A machine learning-trained multimodal MRI model comprising alterations of VBM, MTR, OBV and DCE-MRI parameters mainly in the limbic system regions predicted TTS in SLE patients (r = 0.644, P < 0.0005). CONCLUSION: Multimodal brain MRI demonstrated increased right amygdala perfusion that was associated with better neurocognitive performance in young SLE patients without statistically significant BBB leakage and microstructural abnormalities. A machine learning-constructed multimodal model comprising microstructural, perfusion and permeability parameters accurately predicted neurocognitive performance in SLE patients.

Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study.

OBJECTIVE: To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). METHODS: A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. CONCLUSION: About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.

Evaluating the Construct of Damage in Systemic Lupus Erythematosus.

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI. METHODS: We conducted a 3-part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group. RESULTS: Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life-course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment. CONCLUSION: We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING).

BACKGROUND: Studies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. METHODS: A national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. FINDINGS: 4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53-65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5-0.8) and 0.7 (0.6-0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2-2.0) and 1.4 (1.2-1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1-2), 1.2 (1.1-1.4) and 1.5 (1.2-1.8) for prednisolone ≤7.5 mg respectively]. INTERPRETATION: There was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study

Abstract Objective To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). Methods A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). Results Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. Conclusion About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.

Latent Class Analysis Identifies Distinct Phenotypes of Systemic Lupus Erythematosus Predictive of Flares after mRNA COVID-19 Vaccination: Results from the Coronavirus National Vaccine Registry for ImmuNe Diseases SINGapore (CONVIN-SING).

We recently reported that messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination was associated with flares in 9% of patients with systemic lupus erythematosus (SLE). Herein, we focused our analysis on patients from a multi-ethnic Southeast Asian lupus cohort with the intention of identifying distinct phenotypes associated with increased flares after mRNA COVID-19 vaccination. METHODS: Six hundred and thirty-three SLE patients from eight public healthcare institutions were divided into test and validation cohorts based on healthcare clusters. Latent class analysis was performed based on age, ethnicity, gender, vaccine type, past COVID-19 infection, interruption of immunomodulatory/immunosuppressive treatment for vaccination, disease activity and background immunomodulatory/immunosuppressive treatment as input variables. Data from both cohorts were then combined for mixed effect Cox regression to determine which phenotypic cluster had a higher risk for time to first SLE flare, adjusted for the number of vaccine doses. RESULTS: Two clusters were identified in the test (C1 vs. C2), validation (C1' vs. C2') and combined (C1″ vs. C2″) cohorts, with corresponding clusters sharing similar characteristics. Of 633 SLE patients, 88.6% were female and there was multi-ethnic representation with 74.9% Chinese, 14.2% Malay and 4.6% Indian. The second cluster (C2, C2' and C2″) was smaller compared to the first. SLE patients in the second cluster (C2 and C2') were more likely to be male, non-Chinese and younger, with higher baseline disease activity. The second cluster (C2″) had more incident flares (hazard ratio = 1.4, 95% confidence interval 1.1-1.9, p = 0.014) after vaccination. A higher proportion of patients in C2″ had immunomodulatory/immunosuppressive treatment interruption for vaccination as compared to patients in C1″ (6.6% vs. 0.2%) (p < 0.001). CONCLUSION: We identified two distinct phenotypic clusters of SLE with different patterns of flares following mRNA COVID-19 vaccination. Caution has to be exercised in monitoring for post-vaccination flares in patients with risk factors for flares such as non-Chinese ethnicity, young age, male gender and suboptimal disease control at the time of vaccination.

Health information use by patients with systemic lupus erythematosus (SLE) pre and during the COVID-19 pandemic.

OBJECTIVE: We conducted an international survey of patients with SLE to assess their access, preference and trust in various health information sources pre-COVID-19 and during the COVID-19 pandemic. METHODS: Patients with SLE were recruited from 18 observational cohorts, and patients self-reporting SLE were recruited through five advocacy organisations. Respondents completed an online survey from June 2020 to December 2021 regarding the sources of health information they accessed in the 12 months preceding (pre-11 March 2020) and during (post-11 March 2020) the pandemic. Multivariable logistic regressions assessed factors associated with accessing news and social media post-11 March 2020, and self-reporting negative impacts from health information accessed through these sources. RESULTS: Surveys were completed by 2111 respondents; 92.8% were female, 76.6% had postsecondary education, mean (SD) age was 48.8 (14.0) years. Lupus specialists and family physicians were the most preferred sources pre-11 March 2020 and post-11 March 2020, yet were accessed less frequently (specialists: 78.5% pre vs 70.2% post, difference -8.3%, 95% CI -10.2% to -6.5%; family physicians: 57.1% pre vs 50.0% post, difference -7.1%, 95% CI -9.2% to -5.0%), while news (53.2% pre vs 62.1% post, difference 8.9%, 95% CI 6.7% to 11.0%) and social media (38.2% pre vs 40.6% post, difference 2.4%, 95% CI 0.7% to 4.2%) were accessed more frequently post-11 March 2020 vs pre-11 March 2020. 17.2% of respondents reported negative impacts from information accessed through news/social media. Those outside Canada, older respondents or with postsecondary education were more likely to access news media. Those in Asia, Latin America or younger respondents were more likely to access social media. Those in Asia, older respondents, males or with postsecondary education in Canada, Asia or the USA were less likely to be negatively impacted. CONCLUSIONS: Physicians, the most preferred and trusted sources, were accessed less frequently, while news and social media, less trusted sources, were accessed more frequently post-11 March 2020 vs pre-11 March 2020. Increasing accessibility to physicians, in person and virtually, may help reduce the consequences of accessing misinformation/disinformation.

Insights into the role of neutrophils in neuropsychiatric systemic lupus erythematosus: Current understanding and future directions.

Central nervous system (CNS) involvement of systemic lupus erythematosus (SLE), termed neuropsychiatric SLE (NPSLE), is a major and debilitating manifestation of the disease. While patients with SLE mostly complain of common neuropsychological symptoms such headache and mild mood disorders that may not even be technically attributed to SLE, many SLE patients present with life-threatening NPSLE syndromes such as cerebrovascular disease, seizures and psychosis that are equally challenging in terms of early diagnosis and therapy. While we are just beginning to unravel some mysteries behind the immunologic basis of NPSLE, advancements in the mechanistic understanding of the complex pathogenic processes of NPSLE have been emerging through recent murine and human studies. The pathogenic pathways implicated in NPSLE are multifarious and various immune effectors such as cell-mediated inflammation, autoantibodies and cytokines including type I interferons have been found to act in concert with the disruption of the blood-brain barrier (BBB) and other neurovascular interfaces. Beyond antimicrobial functions, neutrophils are emerging as decision-shapers during innate and adaptive immune responses. Activated neutrophils have been recognized to be involved in ischemic and infective processes in the CNS by releasing neutrophil extracellular traps (NETs), matrix metalloproteinase-9 and proinflammatory cytokines. In the context of NPSLE, these mechanisms contribute to BBB disruption, neuroinflammation and externalization of modified proteins on NETs that serve as autoantigens. Neutrophils that sediment within the peripheral blood mononuclear cell fraction after density centrifugation of blood are generally defined as low-density neutrophils (LDNs) or low-density granulocytes. LDNs are a proinflammatory subset of neutrophils that are increased with SLE disease activity and are primed to undergo NETosis and release cytokines such as interferon-α and tumor necrosis factor. This review discusses the immunopathogenesis of NPSLE with a focus on neutrophils as a core mediator of the disease and potential target for translational research in NPSLE.

Endothelial function and endothelial progenitor cells in systemic lupus erythematosus.

The observations that traditional cardiovascular disease (CVD) risk factors fail to fully account for the excessive cardiovascular mortality in patients with systemic lupus erythematosus (SLE) compared with the general population have prompted in-depth investigations of non-traditional, SLE-related risk factors that contribute to cardiovascular complications in patients with SLE. Of the various perturbations of vascular physiology, endothelial dysfunction, which is believed to occur in the earliest step of atherosclerosis, has been extensively investigated for its contribution to CVD risk in SLE. Endothelial progenitor cells (EPCs), which play a crucial part in vascular repair, neovascularization and maintenance of endothelial function, are quantitatively and functionally reduced in patients with SLE. Yet, the lack of a unified definition of EPCs, standardization of the quantity and functional assessment of EPCs as well as endothelial function measurement pose challenges to the translation of endothelial function measurements and EPC levels into prognostic markers for CVD in patients with SLE. This Review discusses factors that contribute to CVD in SLE, with particular focus on how endothelial function and EPCs are evaluated currently, and how EPCs are quantitatively and functionally altered in patients with SLE. Potential strategies for the use of endothelial function measurements and EPC quantification as prognostic markers of CVD in patients with SLE, and the limitations of their prognostication potential, are also discussed.

T Cells, Interleukin-2 and Systemic Lupus Erythematosus-From Pathophysiology to Therapy.

The phenotypic and functional complexities of T cells engender complicated and often confusing concepts as to how T cells ignite, accelerate and brake the inflammatory processes involved in systemic lupus erythematosus (SLE), let alone the plasticity of T cells that takes place under different immunological contexts. Nevertheless, being one of the prime survival factors of T cells, interleukin (IL)-2 plays a potentially critical role in many immunological scenarios during the pathophysiological process of SLE. Here, the pathophysiology of lupus T cells and current, as well as ongoing, therapeutic approaches of SLE that involve low-dose IL-2 administration will be highlighted. The mechanisms of IL-2 deficiency in SLE pathophysiology, the effects of low-dose IL-2 on T cells and restoration of lupus manifestations in murine SLE models, as well as the efficacy and safety of clinical trials that evaluated low-dose IL-2-containing regimens in patients with SLE will be discussed.

Type I Interferons in Systemic Lupus Erythematosus: A Journey from Bench to Bedside.

Dysregulation of type I interferons (IFNs) has been implicated in the pathogenesis of systemic lupus erythematosus (SLE) since the late 1970s. The majority of SLE patients demonstrate evidence of type I IFN pathway activation; however, studies attempting to address the relationship between type I IFN signature and SLE disease activity have yielded conflicting results. In addition to type I IFNs, type II and III IFNs may overlap and also contribute to the IFN signature. Different genetic backgrounds lead to overproduction of type I IFNs in SLE and contribute to the breakdown of peripheral tolerance by activation of antigen-presenting myeloid dendritic cells, thus triggering the expansion and differentiation of autoreactive lymphocytes. The consequence of the continuous stimulation of the immune system is manifested in different organ systems typical of SLE (e.g., mucocutaneous and cardiovascular involvement). After the discovery of the type I IFN signature, a number of different strategies have been developed to downregulate the IFN system in SLE patients, finally leading to the successful trial of anifrolumab, the second biologic to be approved for the treatment of SLE in 10 years. In this review, we will discuss the bench to bedside translation of the type I IFN pathway and put forward some issues that remain unresolved when selecting SLE patients for treatment with biologics targeting type I IFNs.

Cytokine Release Syndrome in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Case Series of 25 Patients and Review of the Literature.

Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of immunotherapy. Unlike other immune-related adverse events, CRS triggered by immune checkpoint inhibitors (ICIs) is not well described. The clinical characteristics and course of 25 patients with ICI-induced CRS from 2 tertiary hospitals were abstracted retrospectively from the medical records and analyzed. CRS events were confirmed by 2 independent reviewers and graded using the Lee et al. scale. The median duration of CRS was 15.0 days (Q1; Q3 6.3; 29.8) and 10 (40.0%) had multiple episodes of CRS flares. Comparing the clinical factors and biomarkers in Grades 1-2 and 3-5 CRS, we found that patients with Grades 3-5 CRS had following: (i) had longer time to fever onset [25.0 days (Q1; Q3 13.0; 136.5) vs. 3.0 days (Q1; Q3 0.0; 18.0), p=0.027]; (ii) more cardiovascular (p=0.002), neurologic (p=0.001), pulmonary (p=0.044) and rheumatic (p=0.037) involvement; (iii) lower platelet count (p=0.041) and higher urea (p=0.041) at presentation compared to patients with Grades 1-2 CRS. 7 patients (28.0%) with Grades 1-2 CRS were rechallenged using ICIs without event. 9 patients (36.0%) were treated with pulse methylprednisolone and 6 patients (24.0%) were treated with tocilizumab. Despite this, 3 patients (50%) who received tocilizumab had fatal (Grade 5) outcomes from ICI-induced CRS. Longer time to fever onset, lower platelet count and higher urea at presentation were associated with Grade 3-5 CRS. These parameters may be used to predict which patients are likely to develop severe CRS.

A meta-analysis of clinical manifestations in asian systemic lupus erythematous: The effects of ancestry, ethnicity and gender.

OBJECTIVES: Systemic lupus erythematosus (SLE) in Asians is a unique patient group that has been thought to present with more severe organ involvement in comparison to their non-Asian counterparts. We set out to perform a meta-analysis to compare clinical manifestations between ancestries, with a focus on Southeast Asian ethnicities and gender. MATERIALS AND METHODS: A cross-sectional study was performed in conjunction with a meta-analysis to identify differences in prevalences of SLE clinical manifestations. Searches were conducted on Medline for articles comparing between: (i) Asian and non-Asian ancestry; (ii) Southeast Asian ethnicities (Chinese, Malay and Indian); and (iii) male and female Asians. Using random effects model, effect sizes as odd ratios were pooled with DerSimonian and Laird's model. RESULTS: A total of 13 articles were identified and pooled together with our study for this meta-analysis. Comparing among patients of Asian with Non-Asian/European ancestries, no significance difference was found in severe organ manifestations such as renal and neurological involvement [odds ratio (OR): 1.398, p= 0.320 and OR: 1.224, p= 0.526 respectively]. There was significantly greater proportion of Asian SLE patients with thrombocytopenia compared to non-Asian SLE. Chinese SLE patients were less likely to have oral ulcers compared to Indian SLE patients. Lastly, Asian male SLE patients had greater incidence of renal involvement and thrombocytopenia compared to Asian female SLE patients. CONCLUSIONS: Severe SLE manifestations such as renal and neurological involvement were not significantly more frequent in Asian SLE compared to non-Asian/European SLE in this analysis.

Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio reflect disease activity and flares in patients with systemic lupus erythematosus - A prospective study.

OBJECTIVES: To determine the association between neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with disease activity and flares in an inception cohort of patients with systemic lupus erythematosus (SLE) using a prospective study design. METHODS: Consecutive adult patients (age≥21) who fulfilled the 1997 American College of Rheumatology (ACR) or the 2012 Systemic Lupus International Collaboration Clinic Classification (SLICC) Criteria for SLE were followed every 3 months, with SLE disease activity assessed by using SLEDAI-2K, and disease flares defined and captured by the SELENA-SLEDAI Flare Index (SFI). NLR and PLR were computed from the automated machine-counted blood count differentials. Linear mixed model and generalized estimating equation model were constructed to analyze the associations between NLR/PLR and SLEDAI-2K and disease flares, with multivariate adjustments. RESULTS: Of 290 patients recruited, the median (IQR) duration of follow-up and baseline SLEDAI-2K were 4.7 (3.2-6.1) years and 2 (0.5-3.5), respectively. On multivariable analyses, NLR was shown to be positively and significantly associated with SLEDAI-2K (estimate of coefficient (ß)=0.05, P<0.01) and severe disease flares (odds ratio [OR] 1.05, P<0.05), but not with overall disease flares [OR 1.02, non-significant]. While PLR was shown to be positively associated with SLEDAI-2K [ß=0.09, P<0.05], no statistically significant association between PLR and overall or severe disease flares was found [OR 1.00 and OR 1.06 respectively, non-significant]. CONCLUSION: Derived readily from automated blood count differentials, the NLR potentially serves as a surrogate prospective marker of disease activity and severe disease flares in SLE patients.