Serum interferon-alpha level in first degree relatives of systemic lupus erythematosus patients: Correlation with autoantibodies titers

Shahin, Dina; El-Refaey, Ahmed M; El-Hawary, Amany; Salam, A. Abdel; Machaly, Sherine; Abousamra, Nashwa K.; El-Farahaty, Reham M.

doi:10.1016/j.ejmhg.2011.06.009

Cited by 10 publications

(10 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No such effects were observed in splenocytes of mice treated with the control peptide. In spite of the limited sensitivity of the ELISA assay, the levels of IFN-α (56.83±1.4 pg/ml) detected in sera of vehicle treated mice were similar to those reported for the sera of SLE patients [32]. As can been seen in Figure 1B, treatment with hCDR1 but not with the control peptide decreased significantly (p = 0.028) the sera levels of IFN-α.…”

Section: Resultssupporting

confidence: 83%

The Tolerogenic Peptide, hCDR1, Down-Regulates the Expression of Interferon-α in Murine and Human Systemic Lupus Erythematosus

et al. 2013

View full text Add to dashboard Cite

BackgroundThe tolerogenic peptide, hCDR1, ameliorated manifestations of systemic lupus erythematosus (SLE) via the immunomodulation of pro-inflammatory and immunosuppressive cytokines and the induction of regulatory T cells. Because type I interferon (IFN-α) has been implicated to play a role in SLE pathogenesis, we investigated the effects of hCDR1 on IFN-α in a murine model of SLE and in human lupus.Methodology/Principal Findings(NZBxNZW)F1 mice with established SLE were treated with hCDR1 (10 weekly injections). Splenocytes were obtained for gene expression studies by real-time RT-PCR. hCDR1 down-regulated significantly IFN-α gene expression (73% inhibition compared to vehicle treated mice, p = 0.002) in association with diminished clinical manifestations. Further, hCDR1 reduced, in vitro, IFN-α gene expression in peripheral blood mononuclear cells (PBMC) of 10 lupus patients (74% inhibition compared to medium, p = 0.002) but had no significant effects on the expression levels of IFN-α in PBMC of primary anti-phospholipid syndrome patients or of healthy controls. Lupus patients were treated for 24 weeks with hCDR1 (5) or placebo (4) by weekly subcutaneous injections. Blood samples collected, before and after treatment, were frozen until mRNA isolation. A significant reduction in IFN-α was determined in hCDR1 treated patients (64.4% inhibition compared to pretreatment expression levels, p = 0.015). No inhibition was observed in the placebo treated patients. In agreement, treatment with hCDR1 resulted in a significant decrease of disease activity. IFN-α appears to play a role in the mechanism of action of hCDR1 since recombinant IFN-α diminished the immunomodulating effects of hCDR1 on IL-1β, TGFβ and FoxP3 gene expression.Conclusions/SignificanceWe reported previously that hCDR1 affected various cell types and immune pathways in correlation to disease amelioration. The present studies demonstrate that hCDR1 is also capable of down-regulating significantly (and specifically to lupus) IFN-α gene expression. Thus, hCDR1 has a potential role as a novel, disease specific treatment for lupus.

show abstract

Section: Resultssupporting

confidence: 83%

The Tolerogenic Peptide, hCDR1, Down-Regulates the Expression of Interferon-α in Murine and Human Systemic Lupus Erythematosus

et al. 2013

View full text Add to dashboard Cite

show abstract

“…This was not in agreement with an experimental study showing that sera containing immune complexes containing nucleic acid released by necrotic or late apoptotic cells can activate plasmacytoid dendritic cells and promote type I IFN production which in turn enhances toll like receptor-7 (TLR7) signaling, therefore, forming a positive feedback loop, suggesting a strong association between SLE-associated autoantibodies and serum IFN-α (22). Also, our findings were not consistent with other clinical studies which found that the presence of antibodies specific for dsDNA (9,16,23), RNP and SSA/Ro were associated with the levels of serum IFN-α (10). We found no association between serum IFN-α and the different disease manifestations.…”

Section: Original Papercontrasting

confidence: 95%

“…Both genetic and environmental factors may be important and should be investigated further. One Egyptian study showed high serum IFN-α in SLE patients and their first-degree relatives compared to healthy unrelated controls (23). Another study found a clustering of high serum IFN-α in lupus families com-…”

Section: Original Papermentioning

confidence: 99%

Measurement of serum interferon alpha in Egyptian patients with systemic lupus erythematosus and evaluation of its effect on disease activity: a case-control study

et al. 2020

View full text Add to dashboard Cite

Much evidence highlighted the role of interferon alpha (IFN-α) in systemic lupus erythematosus (SLE) and suggested its possible role in assessing disease activity. We measured serum IFN-α in Egyptian SLE patients in order to determine a cutoff value that can be used to distinguish patients from healthy controls and explored its clinical value in monitoring disease activity and different aspects of the disease, in particular lupus nephritis. This cross-sectional, case-control study was conducted on 59 SLE patients and 30 healthy controls. Serum IFN-α was measured in all participants using sensitive enzyme-linked immunosorbent assay (ELISA). SLE patients underwent assessment of disease activity using the SLE disease activity index-2000 (SLEDAI-2K) as well as an evaluation of proteinuria, complement C3 and C4, and serology. Patients with evidence of renal involvement underwent renal biopsy. The median serum IFN-α was 81.8 pg/mL (interquartile range [IQR] 63.4:102.4), which was significantly higher than in healthy controls (median 10.3 pg/mL [IQR 7.3:11.6]) (p<0.001). At serum level of 14.7 pg/mL, IFN-α has high sensitivity and specificity to discriminate SLE patients from controls, with high positive and negative predictive values. Serum IFN-α was not associated with markers of disease activity, clinical features and anti-double stranded DNA. Furthermore, it was not associated with markers of renal activity, including proteinuria, C3 and C4 complement factors and histopathology renal classes. Despite elevated levels of serum IFN-α in SLE patients, it is not possible to use it as a biomarker for disease activity.

show abstract

“…A post hoc threshold of greater than or equal to 19.95 pg/mL was determined to represent high IFN-a production in the media-only control tubes based on in-house optimization assays with healthy controls as well as previous studies measuring healthy adult and pediatric IFN-a blood levels. [17][18][19][20] After the poly(I:C) stimulation, subjects were classified by their response as follows: ''Suppressed'' subjects had low IFN-a levels (<19.95 pg/mL) in their control samples and were unresponsive to poly(I:C) stimulation; ''Peaked'' subjects had high levels of IFN-a (> _19.95 pg/mL) in their control samples, but were unable to mount an additional response to the poly(I:C); and those who ''Responded'' generated an absolute IFN-a increase of at least 11 pg/mL after poly(I:C) stimulation.…”

Section: Cytokine Analysismentioning

confidence: 99%

RIG-I and TLR4 responses and adverse outcomes in pediatric influenza-related critical illness

Novak¹,

Hall

McDonald

et al. 2020

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Background: Decreased TNF-a production in whole blood after ex vivo LPS stimulation indicates suppression of the Toll-like receptor (TLR)4 pathway. This is associated with increased mortality in pediatric influenza critical illness. Whether antiviral immune signaling pathways are also suppressed in these patients is unclear. Objectives: We sought to evaluate suppression of the TLR4 and the antiviral retinoic acid-inducible gene-I (RIG-I) pathways with clinical outcomes in children with severe influenza infection. Methods: In this 24-center, prospective, observational cohort study of children with confirmed influenza infection, blood was collected within 72 hours of intensive care unit admission. Ex vivo whole blood stimulations were performed with matched controls using the viral ligand polyinosinic-polycytidylic acid-low-molecular-weight/LyoVec and LPS to evaluate IFN-a and TNF-a production capacities (RIG-I and TLR4 pathways, respectively). Results: Suppression of either IFN-a or TNF-a production capacity was associated with longer duration of mechanical ventilation and hospitalization, and increased organ dysfunction. Children with suppression of both RIG-I and TLR4 pathways (n 5 33 of 103 [32%]) were more likely to have prolonged (> _7 days) multiple-organ dysfunction syndrome (30.3% vs 8.6%; P 5 .004) or prolonged hypoxemic respiratory failure (39.4% vs 11.4%; P 5 .001) compared with those with single-or no pathway suppression. Conclusions: Suppression of both RIG-I and TLR4 signaling pathways, essential for respective antiviral and antibacterial responses, is common in previously immunocompetent children with influenza-related critical illness and is associated with bacterial coinfection and adverse outcomes. Prospective testing of both pathways may aid in risk-stratification and in immune monitoring.

show abstract

Serum interferon-alpha level in first degree relatives of systemic lupus erythematosus patients: Correlation with autoantibodies titers

Cited by 10 publications

References 46 publications

The Tolerogenic Peptide, hCDR1, Down-Regulates the Expression of Interferon-α in Murine and Human Systemic Lupus Erythematosus

The Tolerogenic Peptide, hCDR1, Down-Regulates the Expression of Interferon-α in Murine and Human Systemic Lupus Erythematosus

Measurement of serum interferon alpha in Egyptian patients with systemic lupus erythematosus and evaluation of its effect on disease activity: a case-control study

RIG-I and TLR4 responses and adverse outcomes in pediatric influenza-related critical illness

Contact Info

Product

Resources

About