Association of Serum C‐Reactive Protein Levels With Lupus Disease Activity in the Absence of Measurable Interferon‐α and a C‐Reactive Protein Gene Variant

Enocsson, Helena; Sjöwall, Christopher; Kastbom, Alf; Eloranta, Maija‐Leena; Rönnblom, Lars; Wetterö, Jonas

doi:10.1002/art.38408

Cited by 34 publications

(29 citation statements)

References 49 publications

(70 reference statements)

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“…Moreover, although serum levels of CRP usually go in parallel with the disease activity in inflammatory states, the results from this point in SLE are inconclusive, being suggested that this autoimmune disease could be an exception (50). In this regard, while some authors have reported moderate levels of CRP (2.1 mg/l) in lupus subjects (51), others have associated this pathology with a high increase (15-16 mg/l) in this acute-phase protein (12). The reasons for this disparity are not entirely clear, however, disease exacerbation could be a determinant factor in this situation.…”

Section: Discusionmentioning

confidence: 99%

Microbiota and oxidant-antioxidant balance in systemic lupus erythematosus

et al. 2017

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ResumenBackground: Systemic lupus erythematosus (SLE) is a chronic infl ammatory disease of autoimmune nature, in which oxidative stress is implicated. Aim: Compare the concentrations of dietary and blood antioxidants, as well as gut microbiota, with serum malondialdehyde (MDA) and C reactive protein (CRP) in 21 subjects suffering from non-active systemic lupus erythematosus (SLE) and 21 age and gender-matched controls. Methods: General biochemical parameters and CRP were determined by enzymatic methods: copper, zinc and selenium by inductively coupled plasma mass spectrometry (ICP-MS), MDA and total antioxidant capacity (TAC) by spectrophotometric methods, gut microbiota by metagenomic analyses and dietary intake by means of food frequency questionnaire. Results: No signifi cant differences were found in diet between lupus patients and the control group, with the exception of trans fatty acids intake, which was higher in patients. In addition, higher concentration of serum copper and lower of zinc in SLE were found. Serum copper was positively associated with CRP and also, this protein with the proportion of Lentisphaerae, Proteobacteria and Verrucomicrobia in feces. Moreover, MDA levels displayed inverse correlations with the Cyanobacteria and Firmicutes groups, while Actinobacteria showed a positive association. The lupus subjects with presence of anti-SSA/Ro were related to higher levels of serum zinc. Conclusion: These results could be useful in the future to go deeper into the understanding of this complex disease. AbstractIntroducción: el lupus eritematoso sistémico es una enfermedad infl amatoria crónica en la que está implicado el estrés oxidativo. Objetivo: evaluar la concentración de antioxidantes de la dieta y sanguíneos, así como de la microbiota sobre las concentraciones de malondialdehído y proteína C reactiva en 21 pacientes de lupus y 21 controles pareados por edad y sexo. Métodos: los parámetros bioquímicos de rutina y proteína C reactiva se determinaron a través de métodos enzimáticos: cobre, zinc y selenio por espectrometría de masas, malondialdehído y capacidad antioxidante total por métodos espectrofotométricos, la microbiota fecal por técnicas metagenómicas y la dieta a través de cuestionarios de frecuencia de consumo. Resultados: no se han observado diferencias en la dieta en los pacientes con lupus respecto al grupo control, excepto en la ingesta de ácidos grasos trans, siendo mayor en el grupo de lupus. En estas pacientes se observaron mayores niveles circulantes de cobre y menores de zinc. La concentración de cobre en suero se relacionó directamente con los niveles de proteína C reactiva y esta proteína, a su vez, con la proporción de Lentisphaerae, Proteobacteria y Verrucomicrobia en heces. Además, mientras que los niveles de malondialdehído se asociaban inversamente con la proporción de Cyanobacteria y Firmicutes, con Actinobacteria se encontró una correlación positiva. La presencia de anti-SSA/Ro en lúpicas se relaciona con mayores concentraciones de zinc. Conclusió...

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Section: Discusionmentioning

confidence: 99%

Microbiota and oxidant-antioxidant balance in systemic lupus erythematosus

et al. 2017

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“…The biological consequences of IFNα that have been implicated in the pathogenesis of lupus have recently been reviewed in detail [121] and include the facilitation of antigen presentation via increased upregulation of class I and II major histocompability complex (MHC), maturation of dendritic cells and stimulation of B cells to become antibody producing plasma cells [122,123]. Although far from all SLE patients have measurable IFNα in serum [124,125], the majority present with increased expression of type I IFN regulated genes, the "type I IFN signature" [126]. [113].…”

Section: Ifnαmentioning

confidence: 99%

“…drug induced lupus [127,128]. Serum levels of IFNα (and/or a presence of type I IFN signature) also correlate with SLE disease activity, and are associated with presence of anti-dsDNA antibodies, nephritis, symptoms from the central nervous system, and hematological manifestations [124,125,129,130]. In addition, GWAS of SLE has revealed a major influence of single nucleotide polymorphisms (SNPs) of IFNα-related genes, such as IRF5, IRF7, IRF8 and STAT4 [12].…”

Section: Introductionmentioning

confidence: 99%

Biomarkers and mediators in systemic lupus erythematosus : IFNα versus the CRP response, and evaluation of suPAR and anti-dsDNA antibody assays

Enocsson¹

2014

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Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which may affect multiple organ systems. Interferon alpha (IFNα) and autoantibodies that form immune complexes with nuclear antigens (ANA) are hallmarks believed to drive the disease into a vicious circle of inflammation, tissue damage, autoantigen exposure and autoantibody production.In SLE, the disease course is characterized by episodes of exacerbations alternating with remissions. In order to best treat the patient it is important to closely monitor symptoms and signs of disease activity. Because of the disease heterogeneity, no single biomarker has yet been found to reflect SLE disease activity in general, although anti-double stranded DNA (anti-dsDNA) antibodies sometimes indicate activity, primarily with renal involvement, and constitutes an item of the SLE disease activity score SLEDAI-2K. However, the method of anti-dsDNA measurement is not standardized and therefore varies between different laboratories. In many other inflammatory conditions, such as rheumatoid arthritis and during bacterial infections, the C-reactive protein (CRP) level is a good indicator of ongoing inflammation, but in SLE and during viral infections, CRP commonly fails to reflect the degree of inflammation. Both viral infections and SLE are characterized by IFNα, and we thus aimed to elucidate whether IFNα can inhibit CRP production. Further, four assays for anti-dsDNA antibody measurements were evaluated with regard to SLE disease specificity and activity, and a new potential biomarker of inflammation, the soluble urokinase plasminogen activator receptor (suPAR), was assessed in relation to disease activity and organ damage.An in vitro inhibitory effect of IFNα on CRP transcription and production was found in hepatocytes, and this was consolidated by in vivo studies of CRP and IFNα in sera from well-characterized SLE patients (KLURING; Kliniskt lupusregister i nordöstra Götaland). Here, CRP and disease activity were associated among patients without IFNα and without a CRP lowering gene variant (SNP rs1205). The poor disease activity compliance of CRP could therefore be explained, at least in part, by polymorphisms in the CRP gene and increased levels of IFNα. Critical differences between the methods measuring anti-dsDNA were found regarding disease specificity and ability to reflect disease activity and the results suggests the Crithidia luciliae immunofluorescence test (CLIFT) for diagnostic purposes and a bead-based multiplex assay (FIDIS) for monitoring of disease activity.

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“…SLE disease activity index-2K), no single biomarker has yet been found to accurately mirror inflammation in each affected organ system [19]. C-reactive protein (CRP) which is frequently used to monitor systemic inflammation in various other conditions, is unfortunately not a reliable read-out of inflammation in SLE or viral infections, most likely due to an IFNα-dependent inhibition of hepatocyte CRP production [20,21]. Another clinical challenge in SLE is to conveniently discriminate ongoing disease activity from irreversible organ damage.…”

Section: Introductionmentioning

confidence: 99%

Soluble urokinase plasminogen activator receptor—A valuable biomarker in systemic lupus erythematosus?

Enocsson¹,

Sjöwall²,

Wetterö³

2015

Clinica Chimica Acta

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The expression of uPAR is mainly regulated by growth factors and pro-inflammatory cytokines like basic fibroblast growth factor, epidermal growth factor, tumor necrosis factor, interleukin ( suPAR as a clinical marker of inflammation and organ damagePlasma membrane expression of uPAR as well as the levels of circulating suPAR have been investigated in relation to a broad range of conditions and suPAR has been referred to as a "molecular crystal ball" due to its prognostic value in diseases like tuberculosis, HIV, sepsis and cancer [2,6,13,26,58,59]. Further, it has been reported that it reflects overall immune activation and systemic inflammation [2]. suPAR has also emerged as a potential biomarker of fibrosis in chronic liver diseases of diverse etiology [10,11,[60][61][62].Recently, suPAR attracted significant attention in primary focal segmental glomerulosclerosis (FSGS). data from this pilot study revealed significantly higher suPAR levels among patients with moderately or highly elevated SDI after study inclusion, compared to patients without SDI increase (Figure 2).Furthermore, there were higher death rates among patients in the two groups with SDI increase (Figure 2). However, it is well known that present organ damage predicts further organ damage [17,100], and thus, adjustment for SDI at baseline should be performed to reduce the risk of bias. A stepwise linear multiple regression analysis was therefore performed to evaluate the impact of suPAR on future SDI increase. After adjusting for age, sex and SDI at study inclusion, we found suPAR levels to have a significant impact on future SDI increase (p = 0.005, standardized β = 0.20) whereas SDI at study inclusion was excluded from the model. Since recent studies have revealed an inverse correlation between serum suPAR and glomerular filtration [67,68,96], we also included estimated glomerular filtration (eGFR) (calculated by the 4-variable Modification of Diet in Renal Disease StudyGroup formula [101]) in the analysis, but eGFR was not retained in the model. From these results, we suggest that suPAR can actually predict organ damage independent of present SDI score or eGFR, but that a prospective study examining the association between suPAR levels at the time of diagnosis with future SDI would be preferable.In line with these findings, elevated suPAR levels have previously been demonstrated to associate with the risk of developing cancer, cardiovascular disease and type 2 diabetes later in life in the general population [7]. Importantly, these associations were independent of CRP, which is known for its predictive value in cardiovascular disease [7,102].7 Potential roles of suPAR in SLE pathogenesisAssessment of circulating suPAR levels at the clinical laboratory could possibly become a future way to estimate organ damage in SLE, and suPAR would be an even more appealing biomarker candidate if the levels could be mechanistically linked to the disease. The pathogenesis of SLE is notoriously complex and not fully understood, but includes disturbances in t...

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Association of Serum C‐Reactive Protein Levels With Lupus Disease Activity in the Absence of Measurable Interferon‐α and a C‐Reactive Protein Gene Variant

Cited by 34 publications

References 49 publications

Microbiota and oxidant-antioxidant balance in systemic lupus erythematosus

Microbiota and oxidant-antioxidant balance in systemic lupus erythematosus

Biomarkers and mediators in systemic lupus erythematosus : IFNα versus the CRP response, and evaluation of suPAR and anti-dsDNA antibody assays

Soluble urokinase plasminogen activator receptor—A valuable biomarker in systemic lupus erythematosus?

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