scholarly journals Urine peptidomic biomarkers for diagnosis of patients with systematic lupus erythematosus

Lupus ◽  
2017 ◽  
Vol 27 (1) ◽  
pp. 6-16 ◽  
Author(s):  
M Pejchinovski ◽  
J Siwy ◽  
W Mullen ◽  
H Mischak ◽  
M A Petri ◽  
...  

Background Systematic lupus erythematosus (SLE) is characterized with various complications which can cause serious organ damage in the human body. Despite the significant improvements in disease management of SLE patients, the non-invasive diagnosis is entirely missing. In this study, we used urinary peptidomic biomarkers for early diagnosis of disease onset to improve patient risk stratification, vital for effective drug treatment. Methods Urine samples from patients with SLE, lupus nephritis (LN) and healthy controls (HCs) were analyzed using capillary electrophoresis coupled to mass spectrometry (CE-MS) for state-of-the-art biomarker discovery. Results A biomarker panel made up of 65 urinary peptides was developed that accurately discriminated SLE without renal involvement from HC patients. The performance of the SLE-specific panel was validated in a multicentric independent cohort consisting of patients without SLE but with different renal disease and LN. This resulted in an area under the receiver operating characteristic (ROC) curve (AUC) of 0.80 ( p < 0.0001, 95% confidence interval (CI) 0.65–0.90) corresponding to a sensitivity and a specificity of 83% and 73%, respectively. Based on the end terminal amino acid sequences of the biomarker peptides, an in silico methodology was used to identify the proteases that were up or down-regulated. This identified matrix metalloproteinases (MMPs) as being mainly responsible for the peptides fragmentation. Conclusions A laboratory-based urine test was successfully established for early diagnosis of SLE patients. Our approach determined the activity of several proteases and provided novel molecular information that could potentially influence treatment efficacy.

2019 ◽  
Vol 79 (3) ◽  
pp. 363-369 ◽  
Author(s):  
Sarah Reid ◽  
Andrei Alexsson ◽  
Martina Frodlund ◽  
David Morris ◽  
Johanna K Sandling ◽  
...  

ObjectivesTo investigate associations between a high genetic disease risk and disease severity in patients with systemic lupus erythematosus (SLE).MethodsPatients with SLE (n=1001, discovery cohort and n=5524, replication cohort) and healthy controls (n=2802 and n=9859) were genotyped using a 200K Immunochip single nucleotide polymorphism array. A genetic risk score (GRS) was assigned to each individual based on 57 SLE risk loci.ResultsSLE was more prevalent in the high, compared with the low, GRS-quartile (OR 12.32 (9.53 to 15.71), p=7.9×10–86 and OR 7.48 (6.73 to 8.32), p=2.2×10–304 for the discovery and the replication cohorts, respectively). In the discovery cohort, patients in the high GRS-quartile had a 6-year earlier mean disease onset (HR 1.47 (1.22 to 1.75), p=4.3×10–5), displayed higher prevalence of damage accrual (OR 1.47 (1.06 to 2.04), p=2.0×10–2), renal disorder (OR 2.22 (1.50 to 3.27), p=5.9×10–5), anti-dsDNA (OR 1.83 (1.19 to 2.81), p=6.1×10–3), end-stage renal disease (ESRD) (OR 5.58 (1.50 to 20.79), p=1.0×10–2), proliferative nephritis (OR 2.42 (1.30 to 4.49), p=5.1×10–3), anti-cardiolipin-IgG (OR 1.89 (1.13 to 3.18), p=1.6×10–2), anti-β2-glycoprotein-I-IgG (OR 2.29 (1.29 to 4.06), p=4.8×10–3) and positive lupus anticoagulant test (OR 2.12 (1.16 to 3.89), p=1.5×10–2) compared with patients in the low GRS-quartile. Survival analysis showed earlier onset of the first organ damage (HR 1.51 (1.04 to 2.25), p=3.7×10–2), first cardiovascular event (HR 1.65 (1.03 to 2.64), p=2.6×10–2), nephritis (HR 2.53 (1.72 to 3.71), p=9.6×10–7), ESRD (HR 6.78 (1.78 to 26.86), p=6.5×10–3) and decreased overall survival (HR 1.83 (1.02 to 3.30), p=4.3×10–2) in high to low quartile comparison.ConclusionsA high GRS is associated with increased risk of organ damage, renal dysfunction and all-cause mortality. Our results indicate that genetic profiling may be useful for predicting outcomes in patients with SLE.


2012 ◽  
Vol 39 (3) ◽  
pp. 516-523 ◽  
Author(s):  
ELEFTHERIA P. GRIKA ◽  
PANAYIOTIS D. ZIAKAS ◽  
ELIAS ZINTZARAS ◽  
HARALAMPOS M. MOUTSOPOULOS ◽  
PANAYIOTIS G. VLACHOYIANNOPOULOS

Objective.To describe morbidity, organ damage, mortality, and cause of death in patients with antiphospholipid syndrome (APS).Methods.Descriptive analysis of 135 patients. Patients were clustered according to initial event: arterial thrombosis including stroke (AT; n = 46), venous thrombosis including pulmonary emboli (VT; n = 53), or pregnancy morbidity (PM; n = 36). Disease progression according to initial event and prevalence of organ damage was observed.Results.APS occurs among young individuals (mean age 33.3 ± 11.9 yrs). One-third of the patients have APS secondary to systemic lupus erythematosus (SLE) or SLE-like disease. A broad spectrum of clinical manifestations mark the disease onset even before diagnosis. The pattern of initial presentation is preserved with regard to second event; VT is followed by VT (84%), AT is followed by AT (95%), and PM is followed by PM (88.9%). The highest morbidity is attributed to neurologic damage. PM is more likely to be followed by a second event, yet is associated with less organ damage than AT and VT. After a mean followup of 7.55 years, 29% of patients experienced organ damage and 5 died, with Systemic Lupus International Collaborating Clinics score associated with increased mortality (HR 1.31, 95% CI 1.07–1.60, p = 0.01, per 1-unit increase); hematological malignancies occurred in 2 patients after a cumulative followup of 1020 person-years. Coexistent SLE adds significant damage in patients with APS.Conclusion.APS is a disease of young individuals, who experience increased morbidity. Neurologic damage is the most common cause of morbidity. AT at presentation as well as coexistent SLE are associated with poor outcome.


2021 ◽  
Vol 22 (13) ◽  
pp. 7143
Author(s):  
María Morell ◽  
Francisco Pérez-Cózar ◽  
Concepción Marañón

The kidney is one of the main organs affected by the autoimmune disease systemic lupus erythematosus. Lupus nephritis (LN) concerns 30–60% of adult SLE patients and it is significantly associated with an increase in the morbidity and mortality. The definitive diagnosis of LN can only be achieved by histological analysis of renal biopsies, but the invasiveness of this technique is an obstacle for early diagnosis of renal involvement and a proper follow-up of LN patients under treatment. The use of urine for the discovery of non-invasive biomarkers for renal disease in SLE patients is an attractive alternative to repeated renal biopsies, as several studies have described surrogate urinary cells or analytes reflecting the inflammatory state of the kidney, and/or the severity of the disease. Herein, we review the main findings in the field of urine immune-related biomarkers for LN patients, and discuss their prognostic and diagnostic value. This manuscript is focused on the complement system, antibodies and autoantibodies, chemokines, cytokines, and leukocytes, as they are the main effectors of LN pathogenesis.


Lupus ◽  
2022 ◽  
pp. 096120332110697
Author(s):  
Megan P Cann ◽  
Anne M Sage ◽  
Elizabeth McKinnon ◽  
Senq-J Lee ◽  
Deborah Tunbridge ◽  
...  

Objectives Systemic Lupus Erythematosus (SLE) is a serious autoimmune disease often resulting in major end-organ damage and increased mortality. Currently, no data exists focussing on the presentation, long-term management and progression of SLE in the Australian paediatric population. We conducted the first Australian longitudinal review of childhood SLE, focussing on response to treatment and outcomes. Methods Detailed clinical and laboratory data of 42 children diagnosed with SLE before 16 years from 1998 to 2018 resident in Western Australia was collected. Data was collected at diagnosis and key clinical review time points and compared using the Systemic Lupus Collaborating Clinics (SLICC) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) criteria. End organ damage was assessed against Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Incidence rates of disease complications and end organ damage were determined. Results Of the 42 children, 88% were female with average age at diagnosis of 12.5 years. Indigenous Australians were over represented with an incidence rate 18-fold higher than non-Indigenous, although most children were Caucasian, reflecting the demographics of the Australian population. Median duration of follow-up was 4.25 years. On final review, 28.6% had developed cumulative organ damage as described by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (incidence rate: 0.08/PY (95% CI 0.04–0.14)), and one child died. Twenty-nine children had renal involvement (incidence rate: 0.38/PY (95% CI 0.26–0.56)). Of the 27 patients with biopsy proven lupus nephritis, 70% had Class III or IV disease. Average length of prednisolone use from diagnosis was 32.5 months. Hydroxychloroquine ( n = 36) and mycophenolate mofetil ( n =21) were the most widely used steroid sparing agents. 61.9% received rituximab and/or cyclophosphamide. Conclusion This is the first longitudinal retrospective review of Australian children with SLE, with a markedly higher incidence in Indigenous children. Although improving, rates of end organ complications remain high, similar to international cohort outcomes. Longitudinal multi-centre research is crucial to elucidate risk factors for poor outcomes, and identifying those warranting early more aggressive therapy.


2019 ◽  
Vol 46 (5) ◽  
pp. 492-500 ◽  
Author(s):  
Lina Wirestam ◽  
Helena Enocsson ◽  
Thomas Skogh ◽  
Leonid Padyukov ◽  
Andreas Jönsen ◽  
...  

Objective.In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes.Methods.We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively.Results.Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01).Conclusion.The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.


2018 ◽  
Vol 6 (4) ◽  
pp. 102
Author(s):  
Gioulia Romanidou ◽  
Theocharis Konstantinidis ◽  
Odysseas Koutsogiannis ◽  
Anastasia Grapsa ◽  
Konstantina Kantartzi ◽  
...  

Antiphospholipid syndrome (APS) is a multifactorial, autoantibody-mediated disease. Antiphospholipid antibodies (aPL) directed against negatively charged phospholipids or various combinations of phospholipid-binding proteins seem to be an independent pathogenic factor that plays a critical role in APS. Unfortunately, their role in hypertension is not fully elucidated. The aim of our study was to determine aPL titers in hypertension patients and investigate the association of aPL with renal impairment parameters. Forty-seven patients with arterial hypertension (22 males, 46.8% and 25 females, 53.2%), aged 41–85 years old (mean 65.9 ± 10.1 years), and 21 age-sex-matched subjects without severe hypertension as control group (8 males, 13 females, 38.1% vs. 61.9%), mean age 61 ± 11.3 years, were enrolled in this study. Patients with other risk factors like Rheumatoid Arthritis and Systematic Lupus Erythematosus (SLE), both viral and bacterial acute infections, and cancer were excluded from the study. The aPL (anticardiolipin (ACA) and anti-b2GPI antibodies, IgG and IgM) were measured by ELISA (Aesculisa, Aesku Diagnostics, Wendelsheim, Germany) with a cutoff of 15 GPL/MPL for ACA and 15 U/mL for b2GPI. Serum Neutrophil gelatinase-associated lipocalin (sNGAL) was measured by ELISA kits (BioVendor, Brno, Czech Republic). Biochemical analysis such as serum creatinine (Cr), were measured by automated analyzer and finally estimated glomerular filtration rate (e-GFR) was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Fifteen patients were positive for ACA IgG (31.9%), two for anti-b2GPI IgM (4.2%), and three for anti-b2GPI IgG (6.3%). Furthermore, three persons from control group were positive in anti-b2GPI IgG (14.27%). The serum level of anti-b2GPI IgG was significantly higher in patients compared to healthy controls (p = 0.013). The level of sNGAL (59.63 ± 41.5 ng/mL vs. 45.5 ± 21.5 ng/mL, p = 0.14) was not higher in hypertensive patients than in the age-sex-matched control group. Additionally, the sNGAL level was found to be directly and positively correlated in patients with positive ACA IgG (r2 = 0,945, p < 0.0001). These results demonstrate that autoimmunity may be one of the pathogenetic factors of hypertension and aPL antibodies might be a potential marker of renal involvement.


Lupus ◽  
2021 ◽  
pp. 096120332098425
Author(s):  
Joseph S Massias ◽  
Eve MD Smith ◽  
Eslam Al-Abadi ◽  
Kate Armon ◽  
Kathryn Bailey ◽  
...  

Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease. Patients diagnosed with juvenile-onset SLE (jSLE), when compared to individuals with adult-onset SLE, develop more severe organ involvement, increased disease activity and greater tissue and organ damage. In adult-onset SLE, clinical characteristics, pathomechanisms, disease progression and outcomes do not only vary between individuals and age groups, but also ethnicities. However, in children and young people, the influence of ethnicity on disease onset, phenotype and outcome has not been investigated in detail. In this study, we investigated clinical and laboratory characteristics in pediatric SLE patients from different ethnic backgrounds (White Caucasian, Asian, Black African/Caribbean) accessing data from a national cohort of jSLE patients (the UK JSLE Cohort Study). Among jSLE patients in the UK, ethnicity affects both the disease’s clinical course and outcomes. At diagnosis, Black African/Caribbean jSLE patients show more “classical” laboratory and clinical features when compared to White Caucasian or Asian patients. Black African/Caribbean jSLE patients exhibit more renal involvement and more frequently receive cyclophosphamide and rituximab. Studies targeting ethnicity-specific contributors to disease expression and phenotypes are necessary to improve our pathophysiological understanding, diagnosis and treatment of jSLE.


Rheumatology ◽  
2019 ◽  
Vol 59 (9) ◽  
pp. 2237-2249 ◽  
Author(s):  
Ioannis Parodis ◽  
Sirisha Gokaraju ◽  
Agneta Zickert ◽  
Kamala Vanarsa ◽  
Ting Zhang ◽  
...  

Abstract Objectives We investigated the cell adhesion molecules (CAMs) Vascular CAM 1 (VCAM-1) and Activated Leucocyte CAM (ALCAM) as urinary biomarkers in SLE patients with and without renal involvement. Methods Female SLE patients (n = 111) and non-SLE population-based controls (n = 99) were enrolled. We measured renal activity using the renal domain of the BILAG index and urine (U) and plasma (P) concentrations of soluble (s)VCAM 1 and U-sALCAM using ELISA. U-sCAM levels were next corrected by U-creatinine. Results U-sVCAM-1/creatinine and U-sALCAM/creatinine ratios were higher in SLE patients vs non-SLE controls (P &lt; 0.001 for both), as well as in patients with active/low-active (BILAG A–C; n = 11) vs quiescent (BILAG D; n = 19) LN (P = 0.023 and P = 0.001, respectively). U-sALCAM/creatinine but not U-sVCAM-1/creatinine ratios were higher in patients with nephritis history (BILAG A–D; n = 30) vs non-renal SLE (BILAG E; n = 79) (P = 0.014). Patients with baseline U-sVCAM-1/creatinine ratios ≥75th percentile showed a 23-fold increased risk of a deterioration in estimated glomerular filtration rate by ≥25% during a 10-year follow-up (odds ratio: 22.9; 95% CI: 2.8, 189.2; P = 0.004); this association remained significant after adjustments for age, disease duration and organ damage. Traditional markers including anti-dsDNA antibodies did not predict this outcome. Conclusion While high U-sVCAM-1 levels appear to reflect SLE disease activity, sALCAM might have particular importance in renal SLE. Both U-sVCAM-1 and U-sALCAM showed ability to distinguish SLE patients with active renal involvement from patients with quiescent or no prior nephritis. High U-sVCAM-1 levels may indicate patients at increased risk for long-term renal function loss.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 266.1-266
Author(s):  
C. Di Mario ◽  
L. Petricca ◽  
M. R. Gigante ◽  
S. Costanzi ◽  
G. Vischini ◽  
...  

Background:Epigenetic factors such as non-coding RNA (miRNA) have been shown to be deregulated in Systemic Lupus Erythematosus (SLE). In mouse models, different miRNAs have been associated with lupus nephritis (LN), one of the most severe manifestations of the disease1.Objectives:To evaluate the expression of miR-155 and miR-34a in renal tissues as biomarkers of organ involvement and inflammatory tissue activity in patients with LN.Methods:Thirty-two SLE patients with LN (age: 32.2 ± 9.2 years) with active renal involvement undergoing ultrasound-guided renal biopsy were enrolled between 2010 and 2019. The nephritic manifestation was present in 13 (41%) patients at disease onset (early-LN SLE), while 19 (59%) patients showed a renal involvement after disease onset (long-LN SLE, mean disease duration at LN onset: 7.3 ± 5.7 years). Twelve age-matched patients with IgA nephropathy were enrolled as control group. Clinical, laboratory and demographic data were collected for each patient. Disease activity was recorded using SLEDAI-2K and renal activity, using the total SLEDAI-2K fraction including the items related to the renal involvement. MiR-155 and miR-34a expression in renal tissues was carried out by extraction of total RNA from paraffin-preserved biopsies and was evaluated, after a retrotrascription protocol, using real-time PCR by relative quantification considering the ΔCt (Ct miRNA- Ct housekeeping gene)2.Results:MiR-155 and miR-34a expression in renal tissues was higher in LN-SLE patients as compared to IgA nephropathy patients (ΔCt miR-155: 9.4 ± 10.1 vs 21.9 ± 3.6, p<0.01; ΔCt miR-34a: 10.1 ± 9.8 vs 19.2 ± 3.1, p=0.02). MiR-155 and miR-34a expression in LN-SLE patients renal tissues was comparable in the different histological classes. Furthermore, a direct correlation was observed between the expression of miR-155 and miR-34a (r = 0.91, p <0.001). Dividing patients based on nephritic onset, SLE patients with long-LN showed higher expression of miR-155 (ΔCt 6.1 ± 8.7) and miR-34a (ΔCt 7.1 ± 9.0) as compared to patients with early-LN (miR-155: ΔCt 13.4 ± 10.6 p = 0.08; miR-34a: ΔCt 15.1 ± 9.5 p = 0.02) or patients with IgA nephropathy (miR-155 p<0.01 and miR-34a p<0.01). Moreover, in early-LN SLE it was observed an inverse correlation between miR-34a expression and C3 and C4 complement components (r=-0.7.2; p=0.05 and r=-0.86; p=0.01, respectively) and a direct correlation between miR-155 and 24h-UP (r=0,67; p=0.03). Considering SLE patients with early-LN, the expression of miR-34a was slightly significant in patients who had relapsed (ΔCt 8.2 ± 11.4 vs ΔCt 18.4 ± 7.9 p = 0.08), although no correlation emerged between the expression of miR-155 and miR-34a at the time of the biopsy and with disease activity indices.Conclusion:MiR-155 and miR-34a may represent tissue biomarkers of inflammatory activation in SLE patients with LN; in particular, the higher expression of these miRNA in long-LN and the correlation between miR-155 expression with p24h-UP in early-LN could indicate a possible role of these biomarkers in renal involvement in patients with SLE with later renal onset. The increased expression of miR-34a could give indications of a disease recurrence suggesting a closer monitoring of patients.References:[1]Leiss H et al. Plosone 2017.[2]Alivernini S et al. Nat Commun 2018.Disclosure of Interests:None declared


2021 ◽  
Vol 2 (1) ◽  
pp. 43-47
Author(s):  
Mengtao Li ◽  
Yanhong Wang ◽  
Jiuliang Zhao ◽  
Qian Wang ◽  
Ziqian Wang ◽  
...  

Abstract Objective To describe the overall clinical characteristics of patients from the Chinese SLE Treatment and Research group (CSTAR) registry in the past 10 years. Methods CSTAR registry originated as a multicenter, consecutive, and prospective design launched in 2009. The data were collected online from 304 rheumatology centers, which covered 30 provinces in China. All data were generated and uploaded in the clinic directly without secondary collection, including demographic, clinical manifestations, disease activity (SLEDAI-2K) and organ damage evaluation (SLICC Damage Index), and lab test results. Biological samples were preserved for future study. Meanwhile, data cleaning and validation were managed by a professional backstage statistician. Results A total of 25,147 SLE patients were registered up to Dec 2019. The mean age of disease onset was 31.2 years with the age of confirmed diagnosis at 32.1 years. The male to female rate was 1:11.9. 4.6% were pediatric patients. The most common clinical presentations at entry were oral ulcer (59.4%), arthritis (55.0%), alopecia (43.22%), skin rash (40.0%), and nephritis (33.5%). The mean SLEDAI score at entry was 4 and 32.6% were in moderate to severely active disease. 66.4% and 37.8% of patients were positive for anti-ds-DNA antibody or low complement level. Additionally, 1.1% of patients were with pulmonary arterial hypertension (PAH). The prevalence rate of cerebrovascular disease was 0.3%. A total of 58.2% of patients were in clinical remission when thery were registered. Conclusions The CSTAR registry is the largest ongoing SLE registry in China so far. More than 25,000 SLE patients are registered and nearly 10,000 are in follow-up visits. This registry has provided high-quality data for future studies and will become an infrastructure for domestic and international collaborations.


Sign in / Sign up

Export Citation Format

Share Document