Biomarkers for Childhood-Onset Systemic Lupus Erythematosus

Abulaban, Khalid; Brunner, Hermine I.

doi:10.1007/s11926-014-0471-2

Cited by 25 publications

(27 citation statements)

References 54 publications

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“…The major clinical use of urine proteomics has so far been to identify biomarkers that either predict an impending renal flare (6, 136) or identify response to therapy. There are several longitudinal studies of single urine biomarkers including the chemokine CCL2, the tubular marker lipocalin2, the acute phase protein hepcidin and the TNF-like molecule TWEAK (reviewed (133, 137)). These studies are still preliminary and have not yet been reliably reproduced or tested in the setting of a clinical trial.…”

Section: Identifying Novel Pathways That Contribute To Initiation Andmentioning

confidence: 99%

What is damaging the kidney in lupus nephritis?

2015

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Summary Despite marked improvements in the survival of patients with severe lupus nephritis over the last 50 years the rate of complete clinical remission following immune suppression is less than 50% and renal impairment still occurs in 40% of affected patients. An appreciation of factors leading to the development of chronic kidney disease (CKD) following acute or subacute renal injury in lupus patients is beginning to emerge. Processes that contribute to endstage renal injury include continuing inflammation, activation of intrinsic renal cells, cell stress and hypoxia, metabolic abnormalities, aberrant tissue repair and tissue fibrosis. This understanding is leading to the development of novel or adjunctive therapies that may protect from the secondary non-immune consequences of acute injury. Approaches based on a molecular/proteomic/lipidomic classification of disease should yield new information about the functional basis of disease heterogeneity so that the most effective and least toxic treatment regimens can be formulated for individual patients.

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Section: Identifying Novel Pathways That Contribute To Initiation Andmentioning

confidence: 99%

What is damaging the kidney in lupus nephritis?

2015

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“…The exact mechanism involved in SLE is needed to understand. a lot of work has been done in searching for biomarkers, from the aspects of DNA, mRNA and protein, expecting to illustrate the mechanism of SLE and find ideal biomarkers for diagnosis and as a precaution to SLE [ 3 – 5 ]. However, the underlying mechanism and pathogenesis of SLE are still far away from understanding.…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of mRNA, microRNA and protein in systemic lupus erythematosus-specific induced pluripotent stem cells from urine

Tang

Chen

et al. 2016

BMC Genomics

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BackgroundIn clinical practice, it is difficult to monitor the repeating relapse in patients who have been suffering from systemic lupus erythematosus (SLE). The underlying etiology remains largely unknown.MethodsAiming to understand the pathogenesis of SLE, a detailed study was conducted. Renal tubular cells–derived iPSCs were successfully obtained from the urine of SLE patients and healthy controls. With the purpose to identify simultaneous expression profiling of microRNA, mRNA and protein, Illumina HiSeq™ 2000 System and iTRAQ-coupled 2D LC-MS/MS analysis were utilized in systemic lupus erythematosus-specific induced pluripotent stem cells (SLE-iPSCs) and normal control-iPSCs (NC-iPSCs). The integration of multiple profiling datasets was realized since it could facilitate the identification of non-seed miRNA targets, as well as differentially expressed mRNAs and proteins.ResultsFor this study, profiling datasets of 1099 differentially expressed mRNAs, 223 differentially expressed microRNAs and 94 differentially expressed proteins were integrated. In order to investigate the influence of miRNA on the processes of regulating mRNAs and proteins’ levels, potential targets of differentially expressed mRNAs and proteins were predicted using miRanda, TargetScan and Pictar. Multiple profiling datasets were integrated to facilitate the identification of miRNA targets, as well as differentially expressed mRNAs and proteins. Through gene ontology (GO) analysis of differentially expressed mRNAs and proteins, biological processes that drive proliferation were identified, such as mRNA processing and translation. Western blot and Q-PCR confirmed AK4 protein and mRNA up-regulation. The findings also showed that TAGLN’s protein and mRNA level were down-regulated in SLE-iPSCs, both miR-371a-5p and let-7a-5p in SLE-iPSC were down-regulated and verified using Q-PCR. The up-regulation of AK4 involved in nucleotide biosynthesis suggested a general acceleration of anabolic metabolism induced by down-regulated miR-371a-5p, which might contribute to SLE.ConclusionBased on high throughput analysis, integrated miRNA, mRNA, and protein expression data were generated. Differentially expressed dates were also adopted in conjunction with in-silico tools to identify potential candidates for SLE-iPSCs. Representative miRNA, mRNA and proteins were verified. It was also expected that the knowledge gained from this study can be applied to assess the usefulness of pathogenesis and novel biomarker candidates of SLE, which may develop a new way for SLE diagnosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2809-9) contains supplementary material, which is available to authorized users.

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“…Patients’ and caregivers’ trust in the medical provider is a central component in care of chronic disease [ 43 ]. Initial delays in diagnosis may start a cycle of distrust between health system and patients that persist beyond diagnosis [ 44 ]. The frequency of misdiagnoses also suggests that young people with SLE may remain undiagnosed in the community.…”

Section: Discussionmentioning

confidence: 99%

Missed opportunities for timely diagnosis of pediatric lupus in South Africa: a qualitative study

et al. 2017

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BackgroundSystemic Lupus Erythematosus (SLE) is a serious multisystem autoimmune disease, which is more aggressive in children and people of African descent. In South Africa, pediatric SLE (pSLE) patients are at high risk for severe disease. Similar to pSLE worldwide, South African children and adolescents with SLE require subspecialized medical care. The aim of this study is to describe the care-seeking experiences of families and examine factors that contribute to delays in the diagnosis of pSLE. Specifically, we sought to identify factors to inform interventions that support the timely referral and diagnosis of pediatric SLE patients in South Africa.MethodsIn-depth, semi-structured interviews were conducted with 22 caregivers of pSLE patients recruited from two government hospitals in Cape Town, South Africa in 2014. Interviews were audio-recorded, transcribed, and analyzed for themes related to barriers to diagnosis.ResultsSix themes were identified and classified as either caregiver or health system barriers to diagnosis. Caregiver barriers included lack of knowledge regarding SLE, financial difficulties, and the social stigma of SLE. Health system barriers were lack of trained staff, a complex medical system, and misdiagnosis.ConclusionCaregivers reported missed opportunities for diagnosing pSLE in their children. Raising public awareness may improve caregiver awareness and reduce stigma of pSLE. Improving family education at diagnosis holds potential to increase patient-physician trust and mitigate fear. Education modules for primary care providers at initial point of contact with the health care system may improve recognition of early pSLE and facilitate expedited referral to a specialist.Electronic supplementary materialThe online version of this article (doi:10.1186/s12969-017-0144-6) contains supplementary material, which is available to authorized users.

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Biomarkers for Childhood-Onset Systemic Lupus Erythematosus

Cited by 25 publications

References 54 publications

What is damaging the kidney in lupus nephritis?

What is damaging the kidney in lupus nephritis?

Integrated analysis of mRNA, microRNA and protein in systemic lupus erythematosus-specific induced pluripotent stem cells from urine

Missed opportunities for timely diagnosis of pediatric lupus in South Africa: a qualitative study

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