The model of circulating immune complexes and interleukin-6 improves the prediction of disease activity in systemic lupus erythematosus

Thanadetsuntorn, Chokchai; Ngamjanyaporn, Pintip; Setthaudom, Chavachol; Hodge, Kenneth; Saengpiya, Nisara; Pisitkun, Prapaporn

doi:10.1038/s41598-018-20947-4

Cited by 35 publications

(40 citation statements)

References 31 publications

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“…There were 12 studies enrolling patients from Asian countries (China (28,29,43,46), Japan (42), South Korea (26), Iran (36), Singapore (34), Malaysia (45), Thailand (44), and Turkey (32,33)). The serum IL-6 levels in most eligible studies were measured using enzyme-linked immunosorbent assay (ELISA) kits (23,24,(26)(27)(28)(29)(31)(32)(33)(37)(38)(39)41,(43)(44)(45). The serum IL-6 levels ranged from 4.272±0.4222 to 123.71±81.783 (pg/mL) in SLE patients and 0.93 ± 0.95 to 10.46 ± 4.33 (pg/mL) in healthy controls.…”

Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

“…Serum IL-6 levels between active and inactive SLE patients were compared in 9 studies (24)(25)(26)29,31,39,(41)(42)(43). Additionally, the correlation coefficient between serum IL-6 level and SLE disease activity was reported in 13 studies (24)(25)(26)(29)(30)(31)(35)(36)(37)(38)(39)44,45). Among all included studies, 3 studies focused on children with SLE (25,28,46), and 21 studies focused on adults with SLE (23,24,26,27,(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45).…”

Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

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Serum interleukin-6 level is correlated with the disease activity of systemic lupus erythematosus: a meta-analysis

Ding¹,

Su²,

You³

et al. 2020

Clinics

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Interleukin-6 (IL-6) plays a crucial role in systemic autoimmunity and pathologic inflammation. Numerous studies have explored serum IL-6 levels in systemic lupus erythematosus (SLE) and their correlation with disease activity. Here, we performed a meta-analysis to quantitatively assess the correlation between the serum IL-6 levels and SLE activity. The PubMed and EMBASE databases were thoroughly searched for relevant studies up to September 2019. Standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were used to describe the differences between serum IL-6 levels in SLE patients and healthy controls and between those in active SLE patients and inactive SLE patients. The correlation between the serum IL-6 levels and disease activity was evaluated using Fisher's z values. A total of 24 studies involving 1817 SLE patients and 874 healthy controls were included in this meta-analysis. Serum IL-6 levels were significantly higher in SLE patients than in the healthy controls (pooled SMD: 2.12, 95% CI: 1.21-3.03, Active SLE patients had higher serum IL-6 levels than inactive SLE patients (pooled SMD: 2.12, 95% CI: 1.21-3.03). Furthermore, the pooled Fisher's z values (pooled Fisher's z=0.36, 95% CI: 0.26-0.46, po0.01) showed that there was a positive correlation between the serum IL-6 levels and SLE activity. This study suggested that serum IL-6 levels were higher in patients with SLE than in healthy controls, and they were positively correlated with disease activity when Systemic Lupus Erythematosus Disease Activity Index44 was defined as active SLE. More homogeneous studies with large sample sizes are warranted to confirm our findings due to several limitations in our meta-analysis.

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Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

Serum interleukin-6 level is correlated with the disease activity of systemic lupus erythematosus: a meta-analysis

Ding¹,

Su²,

You³

et al. 2020

Clinics

View full text Add to dashboard Cite

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“…In addition, in ammatory responses and related immune dysregulation could trigger the development of circulating immune complexes (CICs), which leads to endothelial cells damage and organ in ammation through their tissue depositing and through complement system activation (C1q, C3), resulting in thrombotic complications. Moreover, macrophages could phagocytose CICs causing a hyperin ammatory response, typical in COVID-19 patients [14].…”

Section: Introductionmentioning

confidence: 99%

Anti-phospholipids antibodies and immune complexes in COVID-19 patients: a putative role in disease course for anti-annexin-V antibodies

Cristiano

Fortunati

Cherubini

et al. 2020

Preprint

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Introduction: Besides distinctive respiratory and digestive hallmarks, COVID-19 has been recently associated with a high prevalence of pro-inflammatory and hypercoagulable states known as “COVID-19 Associated Coagulopathy” (CAC), corresponding to a worsening in patients’ conditions, whose causes are still to be elucidated. A link between anti-phospholipids antibodies (aPLs) and viral infections has long been suggested. APLs are assessed for Anti-phospholipid Syndrome (APS) diagnosis, characterized by thrombocytopenia, thrombosis and coagulopathy. Furthermore, circulating immune complexes (CICs), arisen upon inflammatory responses and related immune dysregulation, can lead to endothelial cells damage and thrombotic complications.Method: We performed an extended panel including IgG/IgM anti-cardiolipin, IgG/IgM anti-β2-glycoprotein-1, coupled with IgG/IgM anti-prothrombin, IgG/IgM anti-annexin-V on two COVID-19 patient groups (early and late infection time) and a negative control group. IgG CICs analysis followed to evaluate inflammatory status, through a possible complement system activation.Results: Our results showed low positive cases percentage in IgG/IgM anti-cardiolipin and IgG/IgM anti-β2-glycoprotein-1 assays (4.54%, 6.25%, 4.55%; in early infection group, late infection group and control group, respectively); few positive cases in IgG/IgM anti-prothrombin and IgG/IgM anti-annexin-V immunoassays; no IgG CICs positivity in any patient.Conclusions: In conclusion, our data show a low aPLs prevalence, likely excluding an involvement in the pathogenesis of CAC.Interestingly, IgG/IgM anti-prothrombin and anti-annexin-V positive cases, detected in late infection group, suggest that aPLs could temporarily increase or could trigger a “COVID-19-induced-APS-like-syndrome” in predisposed patients.Finally, even though aPLs are transient, they may still have a thrombotic potential in genetically predisposed COVID-19 patients.

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“…There have been a number of studies on the predictive biological markers of SLE ares, including antidouble-stranded DNA antibodies (anti-dsDNA Ab), the complement system, anti-extractable nuclear antigen antibodies (anti-ENA Ab), cytokines, and chemokines [12,13]. For the prediction of infection in SLE patients, conventional biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate (ESR), procalcitonin [PCT]) [14][15][16][17][18] and new markers have been developed [19].…”

Section: Introductionmentioning

confidence: 99%

Differential Parameters between Activity Flare and Acute Infection in Pediatric Patients with Systemic Lupus Erythematosus

Luo

Yang

Lin

et al. 2020

Preprint

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Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. SLE patients are vulnerable to infections. Infections might mimic and even trigger SLE flares. To distinguish acute infection from activity flare always remains a clinical challenge.We aim to explore the approach to differentiate active infection from disease activity in pediatric SLE patients.Methods: Fifty pediatric SLE patients presenting with 185 clinical episodes were collected.The associations betweenrelevant data encompassing both clinical and laboratory parameters and the outcome groups were analyzed using generalized estimating equations (GEEs)facilitatingthe analysis of data collected in longitudinal and repeated-measures designs.We also used a multinomial logistic regression model for simultaneous prediction of different outcome groups. Finally, we ran the GLIMMIX procedure to track trends of changes in parameters over time.Results: These 185 episodes were divided into 4 outcome groups: infected-active (n=102), infected-inactive (n=11), noninfected-active (n=59), and noninfected-inactive (n=13) episodes. Multivariate GEE analysis showed that SDI, SLEDAI-2K, neutrophil‐to‐lymphocyte ratio (NLR), hemoglobin, platelet, RDW-to-platelet ratio (RPR), and C3 are predictive of flare (combined calculated AUC of 0.8964 and with sensitivity of 82.2 % and specificity of 90.9%). Multivariate GEE analysis showed that SDI, fever temperature, CRP, procalcitonin, lymphocyte percentage, NLR, hemoglobin, and renal score in SLEDAI-2k are predictive of infection (combinedcalculated AUC of 0.7886 and with sensitivity of 63.5% and specificity of 89.2%). We developed regression equations for simultaneous prediction of 4 different outcome groups.We could differentiate noninfected-active from infected-active episodes by different change patterns of ESR, NLR, lymphocyte, C3, and C4 over time.Conclusions: The proposed approach could differentiateflares from infections in pediatric SLE patients. Combination of parameters from four different domains simultaneously, including inflammation (CRP, ESR, PCT), hematology (Lymphocyte percentage, NLR, PLR), complement (C3, C4), and clinical status (SLEDAI, SDI), is effective to make appropriate judgement and treatment decisions.

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The model of circulating immune complexes and interleukin-6 improves the prediction of disease activity in systemic lupus erythematosus

Cited by 35 publications

References 31 publications

Serum interleukin-6 level is correlated with the disease activity of systemic lupus erythematosus: a meta-analysis

Serum interleukin-6 level is correlated with the disease activity of systemic lupus erythematosus: a meta-analysis

Anti-phospholipids antibodies and immune complexes in COVID-19 patients: a putative role in disease course for anti-annexin-V antibodies

Differential Parameters between Activity Flare and Acute Infection in Pediatric Patients with Systemic Lupus Erythematosus

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