[106] Healthy first degree relatives of lupus patients have more pronounced serum IFN activity and the levels are more abundant in younger individuals.[107, 108] A combination of risk alleles in the type I signalling pathway (e.g. STAT4 and IRF5) may confer an additive predisposition of disease.[109] It can be inferred that the use of genetic mapping may help predicting the development and severity of disease in the future. Interferon-regulated

chemokines may be employed to monitor disease activity and organ damage.[110, 111] It has also been proposed that type I IFN-inducible mRNA can be used as pharmacodynamic markers to monitor treatment response of anti-IFN therapy in SLE.[112] The use of anti-IFN-α in the treatment of moderately active SLE was examined in a phase I multicentre double-blind randomized this website trial. In that study, the use of sifalimumab (an anti-IFN-α monoclonal antibody) led to a dose-dependent inhibition of type I IFN-induced

mRNA in whole blood and corresponding changes in related proteins in affected skin. Exploratory analyses showed consistent trends towards improvement in disease activity, less requirement of new or escalation of immunosuppressive treatments and fewer flares in sifalimumab-treated patients.[113] Tolerability profile was acceptable and comparable to patients receiving placebo. Tumour necrosis factor-α is expressed as a trimer on cell surface and in soluble form after the activation of macrophages and dendritic cells. Being described to have both protective and deleterious effects in SLE, Thiamine-diphosphate kinase its position in lupus pathogenesis remained controversial. In NZB/W mice, there was diminished www.selleckchem.com/products/Fulvestrant.html production of TNF-α.[114] In some mouse model, the deficiency of TNF-α appeared to provoke lupus-like autoimmunity. While TNF-α defective NZB/W mice develop severe disease manifestations, TNF-α intact NZB/W mice only show modest lupus activity.[115] Conversely, TNF-α concentration was elevated in both sera and renal tissue of MRL/lpr lupus mice and the levels of TNF-α correlated with the severity of kidney disease.[116] Moreover, even

in NZB/W mice, renal expression of TNF-α is escalated in conjunction with kidney inflammation.[117] In MRL/lpr mice, anti-TNF-α therapy led to improvement of joint and lung manifestations.[118, 119] Whether the controversial role of TNF-α in the pathogenesis of murine SLE could be related to the different animal models used remains unclear. The circulating TNF-α level in active SLE patients closely followed the disease activity and elaborated TNF-α expression was seen in the renal parenchymal tissue in patients with lupus nephritis.[29, 120] Nonetheless, conflicting evidence exists in subjects who had received anti-TNF-α therapy for other autoimmune disorders.[121, 122] These individuals developed lupus-like features coupled with elevated anti-nuclear factors, anti-dsDNA and anti-cardiolipin antibodies.