Novel biomarkers for the assessment of paediatric systemic lupus erythematosus nephritis

Koutsonikoli, Artemis; Trachana, Maria; Farmaki, Evangelia; Tzimouli, Vasiliki; Pratsidou-Gertsi, Polixeni; Printza, Nikoleta; Garyphallos, Alexandros; Galanopoulou, Vasiliki; Kanakoudi-Tsakalidou, F.; Papachristou, Fotis

doi:10.1111/cei.12913

Cited by 17 publications

(10 citation statements)

References 41 publications

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“…In particular, we show for the first time the increased levels of HMGB1 in APS patients. Interestingly, we observed this phenomenon not only in secondary APS (elevated levels of HMGB1 during SLE have already been reported) [ 19 , 34 ] but also in primary APS. During pregnancy, proinflammatory stimuli have been associated with higher risk of adverse pregnancy outcomes, such as preterm birth [ 2 , 35 ].…”

Section: Discussionsupporting

confidence: 62%

Elevated Serum Level of HMGB1 in Patients with the Antiphospholipid Syndrome

Manganelli

Capozzi

Truglia

et al. 2017

Journal of Immunology Research

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Pregnancy problems are common in patients with rheumatic disease; indeed, autoimmune disorders and autoantibodies can affect pregnancy progress and lead to maternal complications. Recent studies have highlighted a close association between HMGB1, chronic inflammation, and autoimmune diseases. Thus, in this investigation, we analyzed serum levels of HMGB1, an alarmin which plays a pivotal role in inducing and enhancing immune cell function. Sera from 30 patients with antiphospholipid syndrome (11 primary and 19 secondary APS), 35 subjects with pregnancy morbidity, and 30 healthy women were analysed for HMGB1 and its putative receptor RAGE (sRAGE) by Western blot and for TNF-α by ELISA. Results revealed that APS patients showed significantly increased serum levels of HMGB1, sRAGE, and the proinflammatory cytokine TNF-α, as compared to healthy women. However, also, the pregnancy morbidity subjects showed significantly increased levels of HMGB1 and sRAGE as well as TNF-α compared to healthy women. Our findings suggest that in subjects with pregnancy morbidity, including obstetric APS, elevated levels of HMGB1/sRAGE may represent an alarm signal, indicating an increase of proinflammatory triggers. Further studies are needed to evaluate the role of HMGB1/sRAGE as a possible tool to evaluate the risk stratification of adverse pregnancy outcomes.

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Section: Discussionsupporting

confidence: 62%

Elevated Serum Level of HMGB1 in Patients with the Antiphospholipid Syndrome

Manganelli

Capozzi

Truglia

et al. 2017

Journal of Immunology Research

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“…The authors explained this by interference of anti‐HMGB1 antibodies during ELISA measurement and that anti‐HMGB1 is associated with low serum HMGB1 . However, the present study and several others used the ELISA technique for HMGB1 measurement and did not demonstrate that finding. Another investigation demonstrated that serum HMGB1 levels by Western blot were similar to those measured by ELISA …”

Section: Discussioncontrasting

confidence: 80%

“…The same was noted in adult SLE patients . ESR and C‐reactive protein, as classic markers of inflammation, are not specific markers of SLE activity . We found no significant correlation between serum HMGB1 and total leukocyte or absolute neutrophil and/or lymphocyte counts HMGB1 is actively secreted from activated immune cells such as macrophages, dendritic cells and monocytes and is passively released from injured or necrotic cells .…”

Section: Discussionmentioning

confidence: 44%

“…In concordance with this hypothesis, our results demonstrated significant increase in serum HMGB1 in patients with biopsy‐proven LN than those without LN. Similarly, serum HMGB1 and anti‐C1q were reported to be significantly elevated in children with SLE and LN as compared to healthy controls . It was expected that serum HMGB1 would be higher in proliferative than non‐proliferative LN.…”

Section: Discussionmentioning

confidence: 98%

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Diagnostic value of serum high‐mobility group box‐1 in pediatric systemic lupus erythematosus

et al. 2019

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Background: High-mobility group box-1 (HMGB1) acts as a damage-associated molecular pattern or as an alarmin and it stimulates inflammatory and immunological activities. Aim:We sought to investigate serum HMGB1 protein expression in patients with pediatric systemic lupus erythematosus (pSLE) in relation to the disease characteristics and activity. Patients and methods:This is a controlled cross-sectional study which comprised 50 children and adolescents with Systemic lupus erythematosus (SLE) and 50 age-and sex-matched healthy subjects who served as a control group. Study measurements included clinical assessment, laboratory workup for SLE (complete blood count, erythrocyte sedimentation rate, serum creatinine, creatinine clearance and 24-hour urinary protein, C3 and anti-double-stranded DNA, lupus anticoagulant and anticardiolipin antibodies) and measurement of serum HMGB1 by enzyme-linked immunosorbent assay in patients and controls.Results: Serum HMGB1 expression was significantly higher in the pSLE patients than the control group (P < 0.001). Patients with lupus nephritis (LN) had significantly higher serum HMGB1 as compared to those with normal kidneys (P < 0.04). Serum HMGB1 in LN patients correlated positively to the SLE Disease Activity Index (P < 0.0001), and 24 hours urinary proteins and negatively to creatinine clearance (P < 0.001). At a cut-off point of ≥40 µg/L, serum HMGB1 showed good diagnostic value for pSLE with sensitivity and specificity of 98% and 95%, respectively. Conclusion:Serum HMGB1 seems to be a reliable biomarker for diagnosis of pSLE and monitoring disease status, especially in LN. HMBG1 might prove to be a potential therapeutic target in LN. K E Y W O R D S HMGB1, lupus nephritis, pediatric systemic lupus erythematosus

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“…In fact, diagnosis and appropriate treatments may be delayed, due to non-specific findings in the early phases of disease, thus new biomarkers may improve the management of this life-threating syndrome [39][40][41][42]. Although a rigorous process of validation is needed, the use of novel biomarkers in these patients may help physicians, thus improving diagnosis with early recognition and prompt therapy as well as predicting response to treatment and outcome, as suggested in other rheumatic diseases [43][44][45][46][47].…”

Section: Discussionmentioning

confidence: 99%

H-ferritin and proinflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome

Ruscitti

Cipriani

Benedetto

et al. 2017

Clinical and Experimental Immunology

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Macrophage activation syndrome (MAS) is hyperinflammatory life-threatening syndrome, associated typically with high levels of serum ferritin. This is an iron storage protein including heavy (H) and light (L) subunits, categorized on their molecular weight. The H-/L subunits ratio may be different in tissues, depending on the specific tissue and pathophysiological status. In this study, we analysed the bone marrow (BM) biopsies of adult MAS patients to assess the presence of: (i) H-ferritin and L-ferritin; (ii) CD68 /H-ferritin and CD68 /L-ferritin ; and (iii) interleukin (IL)-1β, tumour necrosis factor (TNF) and interferon (IFN)-γ. We also explored possible correlations of these results with clinical data. H-ferritin, IL-1β, TNF and IFN-γ were increased significantly in MAS. Furthermore, an increased number of CD68 /H-ferritin cells and an infiltrate of cells co-expressing H-ferritin and IL-12, suggesting an infiltrate of M1 macrophages, were observed. H-ferritin levels and CD68 /H-ferritin cells were correlated with haematological involvement of the disease, serum ferritin and C-reactive protein. L-ferritin and CD68 /L-ferritin cells did not correlate with these parameters. In conclusion, during MAS, H-ferritin, CD68 /H-ferritin cells and proinflammatory cytokines were increased significantly in the BM inflammatory infiltrate, pointing out a possible vicious pathogenic loop. To date, H-ferritin and CD68 /H-ferritin were associated significantly with haematological involvement of the disease, suggesting biomarkers assessing severity of clinical picture.

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Novel biomarkers for the assessment of paediatric systemic lupus erythematosus nephritis

Cited by 17 publications

References 41 publications

Elevated Serum Level of HMGB1 in Patients with the Antiphospholipid Syndrome

Elevated Serum Level of HMGB1 in Patients with the Antiphospholipid Syndrome

Diagnostic value of serum high‐mobility group box‐1 in pediatric systemic lupus erythematosus

H-ferritin and proinflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome

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