Proteomic analysis of human plasma and peripheral blood mononuclear cells in Systemic Lupus Erythematosus patients

Pinna, Sara; Pasella, Sara; Deiana, Marta; Baralla, Angela; Mannu, Andrea; Masala, A.; Pileri, Piera Veronica; Deiana, Nicola; Scognamillo, Fabrizio; Pala, Carlo; Zinellu, Angelo; Carru, Ciriaco; Deiana, Luca

doi:10.1016/j.jim.2017.03.019

Cited by 9 publications

(11 citation statements)

References 103 publications

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“…In the present study, we used red cells to evaluate Prx2 and Prx5 membrane association as a marker of membrane oxidation in ASD patients [29–33]. Prx2 and Prx5 are differently expressed in red cells, the former being more abundant than the latter [38, 52, 53]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Plasma peroxiredoxin changes and inflammatory cytokines support the involvement of neuro-inflammation and oxidative stress in Autism Spectrum Disorder

et al. 2019

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Background It has been established that children with Autism Spectrum Disorders (ASD) are affected by oxidative stress, the origin of which is still under investigation. In the present work, we evaluated inflammatory and pro-oxidant soluble signature in non-syndromic ASD and age-matched typically developing (TD) control children. Methods We analyzed leukocyte gene expression of inflammatory cytokines and inflammation/oxidative-stress related molecules in 21 ASD and 20 TD children. Moreover, in another—comparable—group of non-syndromic ASD (N = 22) and TD (N = 21) children, we analyzed for the first time the protein expression of the four members of the antioxidant enzyme family of peroxiredoxins (Prx) in both erythrocyte membranes and in plasma. Results The gene expression of IL6 and of HSP70i, a stress protein, was increased in ASD children. Moreover, gene expression of many inflammatory cytokines and inflammation/oxidative stress-related proteins correlated with clinical features, and appeared to be linked by a complex network of inter-correlations involving the Aryl Hydrocarbon Receptor signaling pathway. In addition, when the study of inter-correlations within the expression pattern of these molecules was extended to include the healthy subjects, the intrinsic physiological relationships of the inflammatory/oxidative stress network emerged. Plasma levels of Prx2 and Prx5 were remarkably increased in ASD compared to healthy controls, while no significant differences were found in red cell Prx levels. Conclusions Previous findings reported elevated inflammatory cytokines in the plasma of ASD children, without clearly pointing to the presence of neuro-inflammation. On the other hand, the finding of microglia activation in autoptic specimens was clearly suggesting the presence of neuro-inflammation in ASD. Given the role of peroxiredoxins in the protection of brain cells against oxidative stress, the whole of our results, using peripheral data collected in living patients, support the involvement of neuro-inflammation in ASD, and generate a rational for neuro-inflammation as a possible therapeutic target and for plasma Prx5 as a novel indicator of ASD severity.

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Section: Resultsmentioning

confidence: 99%

Plasma peroxiredoxin changes and inflammatory cytokines support the involvement of neuro-inflammation and oxidative stress in Autism Spectrum Disorder

et al. 2019

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“…For example, in the 2 studies investigating the PBMCs exposure to low dose radiation [32, 33], there were seven proteins or almost half of the proposed candidates in each of the studies that overlapped between the studies exhibiting great reproducibility. Similarly, two studies investigating sepsis [18–35] and those investigating diabetes and tuberculosis‐diabetes co‐pathogenesis [11–20], also identified mutual candidates. The most promising PBMCs biomarker based on specificity and validation approaches performed, are marked with red circles in Figure 4.…”

Section: Specificity Of Biomarker Candidates In Human Pbmcsmentioning

confidence: 99%

“…there was no difference in secretion of two other measured cytokines such as IL-1 and IL-6 [25]. In another work [13] disease such as amyotrophic lateral scelerosis (ALS) [29]. Biomarkers that can differenciate between the early (≤55 years) and late (≥75 years) ALS onset patients and relevant pathways for feasible therapeutic intervention, were searched.…”

Section: In-gel Proteomic Approachesmentioning

confidence: 99%

“…For example, in the 2 studies investigating the PBMCs exposure to low dose radiation [32,33], there were seven proteins or almost half of the proposed candidates in each of the studies that overlapped between the studies exhibiting great reproducibility. Similarly, two studies investigating sepsis [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] and those investigating diabetes and tuberculosisdiabetes co-pathogenesis [11][12][13][14][15][16][17][18][19][20], also identified mutual candidates.…”

Section: Specificity Of Biomarker Candidates In Human Pbmcsmentioning

confidence: 99%

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Human peripheral blood mononuclear cells: A review of recent proteomic applications

et al. 2022

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Human peripheral blood mononuclear cells (PBMCs) represent a sentinel blood sample which reacts to different pathophysiological stimuli in the form of immunological responses/immunophenotypic changes. The study of molecular content of PBMCs can provide better understanding of immune processes giving the possibility of monitoring the health conditions of the host organism. Proteomic analysis of PBMCs can achieve mentioned goal as important immune-related biomarkers are easily accessible for analysis. PBMCs have been gaining attention in different research areas including preclinical or clinical investigations. In this review, recent applications of proteomic analysis of PBMCs are described and discussed. Approaches are divided based on different proteomic workflows such as in-gel, in-solution and on-filter modes. The effect of various diseases such as autoimmune, cancer, neurodegenerative, viral, metabolic, and various immune stimulations such as radiation, vaccine, corticosteroids over PBMCs proteome, are described with emphasis on promising protein biomarker candidates.

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“…Along with pharmacogenomics and pharmacogenetics, pharmacoproteomics plays an important role in autoimmune diseases related drug targets’ identification and validation [21]. Recently, there are many studies using pharmacoproteomics to search for molecular changes in sorts of biological specimens from patients with SLE [22–27].…”

Section: Introductionmentioning

confidence: 99%

Reversible SAHH inhibitor protects against glomerulonephritis in lupus-prone mice by downregulating renal α-actinin-4 expression and stabilizing integrin-cytoskeleton linkage

Liu

Lin

et al. 2019

Arthritis Res Ther

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BackgroundGlomerulonephritis is one of the major complications and causes of death in systemic lupus erythematosus (SLE) and is characterized by glomerulosclerosis, interstitial fibrosis, and tubular atrophy, along with severe persistent proteinuria. DZ2002 is a reversible S-adenosyl-l-homocysteine hydrolase (SAHH) inhibitor with potent therapeutic activity against lupus nephritis in mice. However, the molecular events underlying the renal protective effects of DZ2002 remained unclear. This study is designed to uncover the molecular mechanisms of DZ2002 on glomerulonephritis of lupus-prone mice.MethodsWe conducted a twice-daily treatment of DZ2002 on the lupus-prone NZB/WF1 mice, and the progression of lupus nephritis and alteration of renal function were monitored. The LC-MS-based label-free quantitative (LFQ) proteomic approach was applied to analyze the kidney tissue samples from the normal C57BL/6 mice and the NZB/WF1 mice treated with DZ2002 or vehicle. KEGG pathway enrichment and direct protein-protein interaction (PPI) network analyses were used to map the pathways in which the significantly changed proteins (SCPs) are involved. The selected proteins from proteomic analysis were validated by Western blot analysis and immunohistochemistry in the kidney tissues.ResultsThe twice-daily regimen of DZ2002 administration significantly ameliorated the lupus nephritis and improved the renal function in NZB/WF1 mice. A total of 3275 proteins were quantified, of which 253 proteins were significantly changed across normal C57BL/6 mice and the NZB/WF1 mice treated with DZ2002 or vehicle. Pathway analysis revealed that 13 SCPs were involved in tight junction and focal adhesion process. Further protein expression validation demonstrated that DZ2002-treated NZB/WF1 mice exhibited downregulation of α-actinin-4 and integrin-linked kinase (ILK), as well as the restoration of β1-integrin activation in the kidney tissues compared with the vehicle-treated ones.ConclusionsOur study demonstrated the first evidence for the molecular mechanism of SAHH inhibitor on glomerulonephritis in SLE via the modulation of α-actinin-4 expression and focal adhesion-associated signaling proteins in the kidney.Electronic supplementary materialThe online version of this article (10.1186/s13075-019-1820-3) contains supplementary material, which is available to authorized users.

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Proteomic analysis of human plasma and peripheral blood mononuclear cells in Systemic Lupus Erythematosus patients

Cited by 9 publications

References 103 publications

Plasma peroxiredoxin changes and inflammatory cytokines support the involvement of neuro-inflammation and oxidative stress in Autism Spectrum Disorder

Plasma peroxiredoxin changes and inflammatory cytokines support the involvement of neuro-inflammation and oxidative stress in Autism Spectrum Disorder

Human peripheral blood mononuclear cells: A review of recent proteomic applications

Reversible SAHH inhibitor protects against glomerulonephritis in lupus-prone mice by downregulating renal α-actinin-4 expression and stabilizing integrin-cytoskeleton linkage

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