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Immunologic findings precede rapid lupus flare after transient steroid therapy.

ABSTRACT: Systemic lupus erythematosus (SLE) flares elicit progressive organ damage, leading to disability and early mortality. This study evaluated clinical and immunologic factors associated with impending flare in the Biomarkers of Lupus Disease study. Autoantibodies and 32 soluble mediators were measured by multiplex assays, immune pathway activation by gene expression module scores, and immune cell subset frequencies and activation states by flow cytometry. After providing baseline samples, participants received transient steroids to suppress disease and were followed until flare. Flare occurred early (within 60 days of baseline) in 21 participants and late (90-165 days) in 13. At baseline, compared to the late flare group, the early flare group had differential gene expression in monocyte, T cell, interferon, and inflammation modules, as well as significantly higher frequencies of activated (aCD11b⁺) neutrophils and monocytes, and activated (CD86^hi) naïve B cells. Random forest models showed three subgroups of early flare patients, distinguished by greater baseline frequencies of aCD11b⁺ monocytes, or CD86^hi naïve B cells, or both. Increases in these cell populations were the most accurate biomarkers for early flare in this study. These results suggest that SLE flares may arise from an overlapping spectrum of lymphoid and myeloid mechanisms in different patients.

SUBMITTER: Lu R

PROVIDER: S-EPMC6565690 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Immunologic findings precede rapid lupus flare after transient steroid therapy.

Lu Rufei R Guthridge Joel M JM Chen Hua H Bourn Rebecka L RL Kamp Stan S Munroe Melissa E ME Macwana Susan R SR Bean Krista K Sridharan Sudhakar S Merrill Joan T JT James Judith A JA

Scientific reports 20190613 1

Systemic lupus erythematosus (SLE) flares elicit progressive organ damage, leading to disability and early mortality. This study evaluated clinical and immunologic factors associated with impending flare in the Biomarkers of Lupus Disease study. Autoantibodies and 32 soluble mediators were measured by multiplex assays, immune pathway activation by gene expression module scores, and immune cell subset frequencies and activation states by flow cytometry. After providing baseline samples, participa ...[more]

PMID: 31197240

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Project description:BackgroundFlare-up of systemic lupus erythematosus (SLE) is a common characteristic that could have deleterious effects on patients' outcome and survival. The aim of this study was to identify the predictors of severe lupus flare.Methods120 patients with SLE were enrolled and followed-up for 23 months. Demographic, clinical manifestations, laboratory parameters and disease activity were recorded at each visit. In addition, presence of severe lupus flare at each visit was evaluated by using the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLE disease activity index (SLEDAI) flare composite index. Predictors of severe lupus flare were obtained by backward logistic regression analyses. Predictors of SLEDAI were obtained by backward linear regression analyses.ResultsDuring the follow-up period, 47 patients had at least one episode of severe lupus flare. Mean (SD) age of patients with severe flare versus no flare was 31.7 (7.89) and 38.3 (8.24) years, respectively (P = 0.001). Ten (62.5%) out of 16 males and 37 (35.5%) out of 104 females had severe flare (P = 0.04). History of lupus nephritis (LN) was recorded in 76.5% and 44% of patients with severe flare and no severe flare, respectively (P = 0.001). Thirty-five (29.2%) patients with high anti-double-stranded DNA (anti-ds-DNA antibody) and 12 (10%) with negative anti-ds-DNA antibody had severe lupus flare (P = 0.02). By multivariable logistic regression analysis, younger age (OR = 0.87, 95% CI 0.80-0.94, P = 0.0001), history of LN (OR = 4.66, 95% CI 1.55-14.002, P = 0.006) and high SLEDAI at the first visit (OR = 1.19, 95% CI 1.026-1.38) were the main predictors of flare. When severe lupus flare after the first visit was used as the outcome variable, similar findings were observed but, SLEDAI, although left among the final predictors in the model, was not significant. SLEDAIs in future visits were mainly predicted by Anti-ds-DNA antibody, 24-h urine protein and arthritis at the first visit.ConclusionSLE patients with younger age, history of previous LN or high baseline SLEDAI, may need closer monitoring and follow up.

Project description:Immune dysregulation in systemic lupus erythematosus (SLE) contributes to increased disease activity. African-American (AA) SLE patients have an increased prevalence of complications from disease flares and end-organ damage that leads to increased morbidity and early mortality. We previously reported alterations in inflammatory and regulatory immune mediator levels prior to disease flare in European American (EA) SLE patients. In the current study, we assessed baseline and follow-up plasma levels of 52 soluble mediators, including innate, adaptive, chemokine, and TNF superfamily members, in AA SLE patients who developed SELENA-SLEDAI defined flare 6 or 12 weeks after baseline assessment. These patients were compared to themselves during a comparable, clinically stable period (SNF, n = 18), or to demographically matched SLE patients without impending disease flare (NF, n = 13 per group). We observed significant (q < 0.05) alterations in 34 soluble mediators at baseline, with increased levels of both innate (IL-1α and type I interferons [IFN]) and adaptive cytokines (Th1-, Th2-, and Th17-type), as well as IFN-associated chemokines and soluble TNF superfamily members weeks before clinical disease flare. In contrast, stable SLE patients exhibited increased levels of the regulatory mediators IL-10 (q ≤ 0.0045) and TGF-β (q ≤ 0.0004). Because heterogeneous immune pathways were altered prior to clinical disease flare, we developed a soluble mediator score that encapsulates all mediators tested. This score is the sum of all log transformed, standardized soluble mediator levels assessed at baseline (pre-flare), weighted by their Spearman correlation coefficients for association with the SELENA-SLEDAI score at time of concurrent flare. While baseline SELENA-SLEDAI scores were similar between flare vs. NF (p = 0.7214) and SNF (p = 0.5387), the SMS was significantly higher in pre-flare SLE patients (Flare vs NF or SNF, p < 0.0001). By capturing alterations in the balance between inflammatory and regulatory mediators associated with SLE pathogenesis, the soluble mediator score approximates the immune status of SLE patients and provides a robust, predictive gauge of impending disease flare.

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Immunologic findings precede rapid lupus flare after transient steroid therapy.

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Immunologic findings precede rapid lupus flare after transient steroid therapy.

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