Clinical associations of proinflammatory cytokines, oxidative biomarkers and vitamin D levels in systemic lupus erythematosus

Abstract

Background The abnormal biological activity of cytokines plays an important role in the pathophysiology of both systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Several studies have highlighted the association of vitamin D and certain pro-inflammatory cytokines with disease activity in SLE. However, there are limited data on the association of vitamin D and antiphospholipid antibodies (aPL) with various proinflammatory biomarkers in these patients and their relative impact on clinical outcomes. Methods The serum levels of several aPL, 25-hydroxy vitamin D, pro-inflammatory cytokines including IFNα, IL-1β, IL-6, IL-8, IP10, sCD40L, TNFα and VEGF were measured in 312 SLE patients from the Jamaican (n-=45) and Hopkins (n=267) Lupus cohorts using commercial Milliplex and ELISA assays. Oxidized LDL/β2glycoprotein antigenic complexes (oxLβ2Ag) and their associated antibodies were also measured in the Jamaican cohort. Healthy controls for oxidative marker and cytokine testing were utilized. Results Abnormally low vitamin D levels were present in 61.4% and 73.3% of Hopkins and Jamaican SLE patients respectively. Median concentrations of IP10, TNFα, sCD40L and VEGF were elevated in both cohorts, oxLβ2Ag and IL-6 were elevated in the Jamaican cohort and IFNα, IL-1β and IL-8 were the same or lower in both cohorts compared to controls. IP10 and VEGF were independent predictors of disease activity, aPL, IP10 and IL-6 were independent predictors of thrombosis and IL-8 and low vitamin D were independent predictors of pregnancy morbidity despite there being no association of vitamin D with pro-inflammatory cytokines. Conclusions Our results indicate that aPL-mediated pro-inflammatory cytokine production is likely a major mechanism of thrombus development in SLE patients. We provide presumptive evidence of the role IL-8 and hypovitaminosis D play in obstetric pathology in SLE but further studies are required to characterize the subtle complexities of vitamin D’s relationship with cytokine production and disease activity in these patients.

Cytokine and autoantibody clusters interaction in systemic lupus erythematosus

“… IL interleukin, G-CSF granulocyte colony-stimulating factor, IFN interferon, TNF tumor necrosis factor a Mean (SD), in pg/mL b Data correspond to those patients with positive values as compared to healthy controls (above the threshold) [ 34 , 35 ] …”

“…b Data correspond to those patients with positive values as compared to healthy controls (above the threshold) [ 34 , 35 ]…”

“…Both IL-6 and IL-8 have been shown to be up-regulated by endothelial cells treated with IgG APLA in vitro [ 46 ]. IL-8 has been associated with pregnancy morbidity in patients with SLE [ 35 ]. The anti-dsDNA antibody up-regulates IL-8 gene expression and elicits activation-induced cell death of human polymorphonuclear neutrophils [ 47 ], and the release of IL-8 [ 48 ].…”

“…For each cytokine, a standard curve was assessed, and concentration of each cytokine was calculated as an interpolation of the standard curve using the FCAP Array™ Software (BD Bioscience™). Results were considered positive when the assay results were above a threshold value, which was confirmed in healthy individuals in whom evidence of acute or chronic disease including autoimmune, cardiovascular, or metabolic was not detected (Table 3 ) [ 34 , 35 ].…”

Immunomodulatory Effects of Diet and Nutrients in Systemic Lupus Erythematosus (SLE): A Systematic Review

“…A significantly high prevalence of vitamin D deficiency has been observed in patients with SLE in Saudi Arabia ( 114 ), Bahrain ( 115 ), the USA ( 116 , 117 ), Canada ( 118 ), Jamaica ( 119 ), Brazil ( 120 ), France ( 121 ), Hungary ( 122 ), Denmark ( 123 ), and Spain ( 124 , 125 ). In clinical studies on patients with SLE, significant inverse correlations were observed between serum levels of vitamin D and SLE disease activity index (SLEDAI) score in Malaysian ( 126 ), Taiwanese ( 127 ), Thai ( 128 ), Indian ( 129 ), Egyptian ( 130 , 131 ), Saudi Arabian ( 132 ), Brazilian ( 133 , 134 ), Australian ( 135 ), American ( 136 ), Hungarian ( 122 ), and Chinese ( 137 ) populations with an exception of Serbian SLE subjects ( n = 46) ( 138 ).…”