Serum activity that confers acid lability to α‐interferon in systemic lupus erythematosus: its association with disease activity and its independence from circulating α‐interferon

Yee, Arthur M.F.; Yip, Y. K.; Fischer, Harry D.; Buyon, Jill P.

doi:10.1002/art.1780330414

Cited by 19 publications

(9 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 Additional studies have since corroborated the presence of raised levels of IFN in patients with active SLE. [3][4][5][6][7][8] Clinically, evidence for a putative role of IFNa in SLE comes from the observation that patients without SLE treated with IFNa occasionally develop autoantibodies and clinical manifestations consistent with SLE. 9 10 More recently, levels of IFNa in patients correlated positively with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores and rash.…”

mentioning

confidence: 99%

Type I interferon correlates with serological and clinical manifestations of SLE

Dall’Era

2005

Annals of the Rheumatic Diseases

254

169

View full text Add to dashboard Cite

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems triggered by the production of autoantibodies. Previous clinical studies in humans and murine models suggest that type I interferons (IFNs) are important for the initiation and potentiation of SLE activity. Methods: 65 consecutive patients with SLE were identified from the University of California, San Francisco Lupus Clinic with moderate-severe disease activity. 94 serological samples were collected. Type I IFN levels and the ability of plasma to induce expression of several surface markers of dendritic cell maturation were measured. Results: Type I IFN levels correlated with the presence of cutaneous manifestations, and there was a trend towards correlation with renal disease. No correlation was found between type I IFN levels and neurological disease. Type I IFN levels correlated positively with the SLEDAI score and anti-dsDNA levels and inversely with C3 levels. Interestingly, type I IFN levels were highest in African American patients. SLE plasma also induced the expression of MHC class I, CD38, and CD123 on monocytes, and was blocked by the addition of a monoclonal antibody to IFNAR1. Conclusions: The pathogenic role of type I IFN is suggested by the induction of cell surface markers for dendritic cell maturation. The potential therapeutic utility of antibodies directed to either type I IFN or IFNAR1/IFNAR2 may be of interest in further studies.

show abstract

mentioning

confidence: 99%

Type I interferon correlates with serological and clinical manifestations of SLE

Dall’Era

2005

Annals of the Rheumatic Diseases

254

169

View full text Add to dashboard Cite

show abstract

“…Type 1 IFN, which is central to the pathogenesis of SLE and mainly produced by the plasmacytoid dendritic cells (pDC), is increased in the majority of patients with SLE [56, 57]. pDC residing in atherosclerotic plaques produce type I IFN which locally induces adjacent CD4+ T cells to express TNF-related apoptosis-inducing ligand (TRAIL) [58].…”

Section: Altered Physiology Of Endothelium In Slementioning

confidence: 99%

Imbalance between Endothelial Damage and Repair: A Gateway to Cardiovascular Disease in Systemic Lupus Erythematosus

Mak

Kow

2014

BioMed Research International

View full text Add to dashboard Cite

Atherosclerosis is accelerated in patients with systemic lupus erythematosus (SLE) and it leads to excessive cardiovascular complications in these patients. Despite the improved awareness of cardiovascular disease and advent of clinical diagnostics, the process of atherogenesis in most patients remains clinically silent until symptoms and signs of cardiovascular complications develop. As evidence has demonstrated that vascular damage is already occurring before clinically overt cardiovascular disease develops in lupus patients, intervention at the preclinical stage of atherogenesis would be plausible. Indeed, endothelial dysfunction, one of the earliest steps of atherogenesis, has been demonstrated to occur in lupus patients even when they are naïve for cardiovascular disease. Currently known “endothelium-toxic” factors including type 1 interferon, proinflammatory cytokines, inflammatory cells, immune complexes, costimulatory molecules, neutrophils extracellular traps, lupus-related autoantibodies, oxidative stress, and dyslipidemia, coupled with the aberrant functions of the endothelial progenitor cells (EPC) which are crucial to vascular repair, likely tip the balance towards endothelial dysfunction and propensity to develop cardiovascular disease in lupus patients. In this review, altered physiology of the endothelium, factors leading to perturbed vascular repair contributed by lupus EPC and the impact of proatherogenic factors on the endothelium which potentially lead to atherosclerosis in lupus patients will be discussed.

show abstract

“…Milestones in linking IFNa to SLE. † IFNa acid lability [41] † Increased IFNa serum levels [42] † IFNa producing cells in blood and tissues [43 -45] † IFNa target gene expression detected by microarrays [43,44] † IFNa-induced genes located at a genomic susceptibility locus in SLE mice [46] † IFNa/b R deficient mice do not develop SLE [47] † IFNa (including IFNa in lupus sera) induces maturation of antigen presenting cells [48] † Induction of IFNa by complexes in SLE sera [45,49] † Autoantibodies/overt SLE induction by therapeutic IFNa [3,23,24,34,35,50] system in spite of their small percentage in the peripheral blood. Immune complexes containing both DNA and RNA may be internalized by pDC through the receptors for the Fc fragments of IgG (FcgRIIa) and can activate the cells via endosomal toll-like receptors (TLR).…”

Section: Interferon Therapy and Slementioning

confidence: 99%

Type I interferon therapy and its role in autoimmunity

2010

View full text Add to dashboard Cite

Interferons (IFNs) display a pleiotropic effect on different cell types of both the innate and the adaptive immunities being able to affect the immune responses. The ability of IFNs, and in particular of type I IFN, to activate dendritic cells and to modulate the expression of major histocompatibility classes I and II molecules supports their potential role also in the development and maintenance of tolerance. When tolerance breakdown has occurred, immunocomplexes generated by the reaction of nuclear antigens and specific autoantibodies can further induce type I IFN production. Accordingly, high acid-labile type I IFN plasma levels, overexpression of IFNalpha-induced transcripts and the association with genes closely related to type I IFN response represent the rationale for the so-called IFN signature in systemic lupus erythematosus, a prototypical autoimmune disease. The role of IFNs in autoimmunity is further supported by their direct and deleterious impact on target tissues. The therapeutic use of IFNs is based on their antiviral and antiproliferative effect. Type I IFN administration, in particular, is associated with the appearance of autoimmunity, although less frequently than expected. Such an event takes place mostly in patients with previous autoimmune manifestations and can be characterized by the appearance of autoantibodies only or of a clinically overt disease. IFN therapy cessation is usually, but not always, required for controlling the autoimmune disorders.

show abstract

Serum activity that confers acid lability to α‐interferon in systemic lupus erythematosus: its association with disease activity and its independence from circulating α‐interferon

Cited by 19 publications

References 13 publications

Type I interferon correlates with serological and clinical manifestations of SLE

Type I interferon correlates with serological and clinical manifestations of SLE

Imbalance between Endothelial Damage and Repair: A Gateway to Cardiovascular Disease in Systemic Lupus Erythematosus

Type I interferon therapy and its role in autoimmunity

Contact Info

Product

Resources

About