Relationship between serum levels of macrophage migration inhibitory factor and the activity of antineutrophil cytoplasmic antibody-associated vasculitides
ABSTRACT Macrophage migration inhibitory factor (MIF) is a central proinflammatory cytokine that regulates innate and adaptive immune responses. To evaluate its role in primary vasculitides, we determined MIF by enzyme-linked immunoassay in the sera of patients with Wegener's granulomatosis (WG; n=26), microscopic polyangiitis (MPA; n=10), polyarteritis nodosa (PAN; n=9) and giant cell arteritis (GCA; n=11). Healthy controls (n=26) and patients with sarcoidosis (n=14) were studied in parallel. Serum levels of MIF were significantly higher in patients with WG (median 41.1, range 3.2-120 ng/ml) than those in healthy controls (6.0, 0.015-36.5 ng/ml; P<0.001) and in patients with sarcoidosis (13.8, 0.015-67.1 ng/ml; P<0.05). MIF values were higher in MPA patients (29.5, 9.9-69.4 ng/ml; P<0.01) in comparison with those in healthy controls. In particular, increased levels of MIF were associated with active disease as assessed by the Birmingham Vasculitis Activity Score. Sequential studies showed decreased levels of MIF after initiation of immunosuppressive therapy, with clinical improvement in WG and MPA patients. In contrast, serum levels of MIF were not significantly elevated in patients with PAN and GCA. The results suggest that MIF contributes to the inflammatory process and correlates with disease activity in antineutrophil cytoplasmic antibody-associated vasculitides.
Article: Giant cell and Takayasu arteritis[Show abstract] [Hide abstract]
ABSTRACT: Giant cell arteritis and Takayasu arteritis are well known large vessel vasculitides with an unknown etiology. As they have similar clinical features, this short article reviews recent advances in clinical and pathophysiological findings, focusing in particular on papers published in the past year. Delayed gadolinium-enhanced magnetic resonance imaging showed delayed hyperenhancement in the aortic wall in Takayasu arteritis. This technique may be useful in monitoring disease activity or inflammation in the arterial wall and can be used for small vessels such as temporal arteries in giant cell arteritis with high-resolution imaging. Evidence is accumulating that antitumor necrosis factor-alpha monoclonal antibody therapy can be useful for patients refractory to corticosteroid and/or immunosuppressant treatment. Functional promoter polymorphisms of genes encoding inducible nitric oxide synthase and I-kappaB-like protein were suggested to be associated with susceptibility to giant cell arteritis and Takayasu arteritis, respectively. Advances in imaging technique will make it possible to evaluate inflammatory activity of the vascular lesions and provide a useful guide for treatment of giant cell arteritis and Takayasu arteritis. Further understanding of the pathophysiological mechanism may contribute to the development of new medicine targeting critical factors in the pathogenesis, such as antitumor necrosis factor-alpha agents.Current Opinion in Rheumatology 02/2007; 19(1):39-43. DOI:10.1097/BOR.0b013e3280119866 · 5.07 Impact Factor
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ABSTRACT: The objective of this study was to analyse levels of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) in patients with primary Sjögren's syndrome (pSS) and to examine associations of MIF with clinical, serological and immunological variables. MIF was determined by ELISA in the sera of 76 patients with pSS. Further relevant cytokines (IL-1, IL-6, IL-10, IFN-gamma and TNF-alpha) secreted by peripheral blood mononuclear cells (PBMC) were determined by ELISPOT assay. Lymphocytes and monocytes were examined flow-cytometrically for the expression of activation markers. Results were correlated with clinical and laboratory findings as well as with the HLA-DR genotype. Healthy age- and sex-matched volunteers served as controls. We found that MIF was increased in patients with pSS compared with healthy controls (p < 0.01). In particular, increased levels of MIF were associated with hypergammaglobulinemia. Further, we found a negative correlation of MIF levels with the number of IL-10-secreting PBMC in pSS patients (r = -0.389, p < 0.01). Our data indicate that MIF might participate in the pathogenesis of primary Sjögren's syndrome. MIF may contribute to B-cell hyperactivity indicated by hypergammaglobulinemia. The inverse relationship of IL-10 and MIF suggests that IL-10 works as an antagonist of MIF in pSS.Arthritis research & therapy 02/2007; 9(2):R43. DOI:10.1186/ar2182 · 4.12 Impact Factor
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ABSTRACT: Increasing evidence supports the concept of macrophage migration inhibitory factor (MIF) as a central proinflammatory cytokine in autoimmune diseases. To further evaluate its role in systemic sclerosis (SSc), serum levels of MIF were determined by enzyme-linked immunoassay, and correlations to clinical manifestations were analyzed in 43 patients. MIF levels were significantly increased in patients (median, 18.8; range, <0.015-189 ng/ml) in comparison to healthy controls (n=43, 8.0, <0.015-36.5 ng/ml; P<0.0005). MIF values were higher in diffuse than in limited cutaneous SSc (P<0.005). Patients with pulmonary hypertension and recurrent digital ulcers showed higher MIF levels than patients without these manifestations (P<0.005). This association was also observed in limited cutaneous SSc. Sequential studies revealed decreased MIF levels after initiation of immunosuppressive therapy. MIF levels were not significantly different in patients with and without macrovascular disease of the peripheral arteries. The results suggest that MIF might contribute to inflammation and vasculopathy in SSc.Clinical Rheumatology 07/2008; 27(10):1307-11. DOI:10.1007/s10067-008-0960-7 · 1.77 Impact Factor