Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassay

Petráčková, Anna; Smrzova, Andrea; Gajdoš, Petr; Schubertová, M.; Schneiderová, Petra; Krömer, Pavel; Snášel, Václav; Skácelová, Martina; Mrázek, František; Zadrazil, J; Horák, Pavel; Kriegová, Eva

doi:10.1186/s12014-017-9167-8

Cited by 39 publications

(18 citation statements)

References 69 publications

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“…IL-18 has also been suggested as a potential predictive biomarker for long-term outcomes in pediatric LN ( 23 ). Renal disease is a major predictor of damage progression in SLE, and our findings of a near-significant association of IL-18 with organ damage in multivariable analysis ( p = 0.07) are supported by previous findings in a smaller study which reported increased serum IL-18 in SLE patients with organ damage ( 53 ). Furthermore, we observed that high baseline serum IL-18 levels were associated with the presence of organ damage at the subsequent visit, suggesting a potential for serum IL-18 as a predictive biomarker for irreversible organ damage.…”

Section: Discussionsupporting

confidence: 90%

Analysis of Serum Interleukin (IL)-1β and IL-18 in Systemic Lupus Erythematosus

et al. 2018

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Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by biological and clinical heterogeneity. The interleukin (IL)-1 superfamily is a group of innate cytokines that contribute to pathogenesis in many autoimmune diseases. IL-1β and IL-18 are two members that have been shown to play a role in murine lupus-like models, but their role in human SLE remains poorly understood. Here, IL-1β and IL-18 were quantified by enzyme-linked immunosorbent assay in the serum of healthy controls (HCs) and SLE patients from a prospectively followed cohort. Disease activity and organ damage were assessed using SLE disease activity index 2000 (SLEDAI-2K) and SLE damage index scores (SDI), respectively. 184 SLE patients (mean age 44.9 years, 91% female, 56% double-stranded deoxyribonucleic acid positive) were compared to 52 HC. SLE patients had median [IQR] SLEDAI-2K of 4 [2,6], and SDI of 1 [0–2]. Serum IL-18 levels were statistically significantly higher in SLE patients compared to HCs. Univariable linear regression analyses showed that patients with active renal disease or irreversible organ damage had statistically significantly elevated serum IL-18 levels. The association between serum IL-18 and active renal disease was confirmed in multivariable analysis after adjusting for ethnicity and organ damage. High baseline serum IL-18 levels were associated with organ damage at the subsequent visit. Serum IL-1β levels were not significantly elevated in SLE patients when compared to HCs and had no association with overall or organ-specific disease activity or organ damage in cross-sectional and longitudinal analyses. Our data suggest that serum IL-18 and IL-1β have different clinical implications in SLE, with IL-18 being potentially associated with active renal disease.

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Section: Discussionsupporting

confidence: 90%

Analysis of Serum Interleukin (IL)-1β and IL-18 in Systemic Lupus Erythematosus

et al. 2018

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“…has been reported earlier. Their association with organ damage has also been documented [44]. A similar finding in pregnant lupus patients hints to an increase in susceptibility to different organ complications, particularly to lupus nephritis.…”

Section: Discussionmentioning

confidence: 60%

Altered Tregs and oxidative stress in pregnancy associated lupus

et al. 2019

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Aim: SLE is a systemic autoimmune disease generally affecting woman in the reproductive age. It is associated with an altered level of Tregs and oxidative stress while an increase in Tregs, and different antioxidant mechanisms to combat oxidative stress are essential for successful pregnancy. Hence, this study aims to determine the level of CD4 + and CD8 + Tregs and oxidative stress in pregnant lupus patients. Methods: Ten healthy and 10 pregnant lupus volunteers from the North Indian population, within the age group of 20-30 years were enrolled in the study. All the patients were non-smokers, non-alcoholics and were not associated or undergoing therapy for any other disease. They had a SLEDAI of 37.4 ± 7.32 with 5.2 ± 1.93 years of disease duration. Oxidative stress was determined by measuring the enzyme activity of anti-oxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) and the level of reduced glutathione and lipids peroxidised, spectrophotometrically. Flowcytometry was performed for immunophenotyping to determine CD8 + and CD4 + Tregs.Results: Elevated CD8 + Tregs and diminished CD4 + Tregs were observed in pregnant lupus patients. Oxidative stress was significantly increased as the activities of anti-oxidant enzymes and level of reduced glutathione was considerably diminished. There was a substantial increase in the amount of lipids peroxidised.Conclusion: Pregnant lupus patients undergo considerable level of oxidative stress in comparison to healthy pregnant woman. The decreased level of CD4 + Tregs and an increase in CD8 + Tregs might be another important factor responsible for pregnancy associated complications. Hence, lupus leads to alterations in the necessary conditions for a successful pregnancy, which might eventually cause higher mortality, morbidity and associated complications.

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“…The protein levels of molecules associated with inflammation and osteoclastogenesis (see S1 Table) were assessed on a 92-plex Targeted Proteomics Chip (Proseek Multiplex Oncology I kit, Olink Bioscience, Uppsala, Sweden) using 1 μl of tissue lysates as reported previously [26, 27]. For sensitivity and specificity parameters, see Assarsson et al [28].…”

Section: Methodsmentioning

confidence: 99%

Inflammation time-axis in aseptic loosening of total knee arthroplasty: A preliminary study

et al. 2019

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Objective Aseptic loosening (AL) is the most frequent long-term reason for revision of total knee arthroplasty (TKA) affecting about 15–20% patients within 20 years after the surgery. Although there is a solid body of evidence about the crucial role of inflammation in the AL pathogenesis, scared information on inflammation signature and its time-axis in tissues around TKA exists. Design The inflammation protein signatures in pseudosynovial tissues collected at revision surgery from patients with AL (AL, n = 12) and those with no clinical/radiographic signs of AL (non-AL, n = 9) were investigated by Proximity Extension Assay (PEA)-Immunoassay and immunohistochemistry. Results AL tissues had elevated levels of TNF-family members sTNFR2, TNFSF14, sFasL, sBAFF, cytokines/chemokines IL8, CCL2, IL1RA/IL36, sIL6R, and growth factors sAREG, CSF1, comparing to non-AL. High interindividual variability in protein levels was evident particularly in non-AL. Levels of sTNFR2, sBAFF, IL8, sIL6R, and MPO discriminated between AL and non-AL and were associated with the time from index surgery, suggesting the cumulative character of inflammatory osteolytic response to prosthetic byproducts. The source of elevated inflammatory molecules was macrophages and multinucleated osteoclast-like cells in AL and histiocytes and osteoclast-like cells in non-AL tissues, respectively. All proteins were present in higher levels in osteoclast-like cells than in macrophages. Conclusions Our study revealed a differential inflammation signature between AL and non-AL stages of TKA. It also highlighted the unique patient’s response to TKA in non-AL stages. Further confirmation of our preliminary results on a larger cohort is needed. Analysis of the time-axis of processes ongoing around TKA implantation may help to understand the mechanisms driving periprosthetic bone resorption needed for diagnostic/preventative strategies.

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Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassay

Cited by 39 publications

References 69 publications

Analysis of Serum Interleukin (IL)-1β and IL-18 in Systemic Lupus Erythematosus

Analysis of Serum Interleukin (IL)-1β and IL-18 in Systemic Lupus Erythematosus

Altered Tregs and oxidative stress in pregnancy associated lupus

Inflammation time-axis in aseptic loosening of total knee arthroplasty: A preliminary study

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