Expression of macrophage migration inhibitory factor in diffuse systemic sclerosis

E Selvi, S A Tripodi, M Catenaccio, S Lorenzini, D Chindamo, S Manganelli, R Romagnoli, F Ietta, L Paulesu, C Miracco, M Cintorino, R Marcolongo, E Selvi, S A Tripodi, M Catenaccio, S Lorenzini, D Chindamo, S Manganelli, R Romagnoli, F Ietta, L Paulesu, C Miracco, M Cintorino, R Marcolongo

Abstract

Objective: To evaluate whether, in patients with the diffuse form of systemic sclerosis (dSSc), macrophage migration inhibitory factor (MIF) production is dysregulated.

Methods: 10 patients with dSSc and 10 healthy controls, matched for age and sex, were studied. MIF expression was evaluated by immunohistochemistry on formalin fixed skin biopsies of patients with dSSc and controls. MIF levels were assayed in the sera and in the supernatants of skin cultured fibroblasts by a colorimetric sandwich enzyme linked immunosorbent assay (ELISA). MIF concentrations in culture medium samples and in serum samples were compared by Student's two tailed t test for unpaired data.

Results: Anti-MIF antibody immunostained the basal and mainly suprabasal keratinocytes. Small perivascular clusters of infiltrating mononuclear cells were positive; scattered spindle fibroblast-like cells were immunostained in superficial and deep dermal layers. The serum concentrations of MIF in patients with dSSc (mean (SD) 10705.6 (9311) pg/ml) were significantly higher than in controls (2157.5 (1288.6) pg/ml; p=0.011); MIF levels from dSSc fibroblast cultures (mean (SD) 1.74 (0.16) ng/2 x 10(5) cells) were also significantly higher than in controls (0.6 (0.2) ng/2 x 10(5) cells; p=0.008).

Conclusion: These results suggest that MIF may be involved in the amplifying proinflammatory loop leading to scleroderma tissue remodelling.

Figures

Figure 1
Figure 1
Serum MIF levels (pg/ml) from 10 patients with dSSc and 10 healthy controls matched for age and sex. The concentration of MIF in patients with dSSc was significantly higher than in controls (p

Figure 2

Supernatant MIF levels from fibroblast…

Figure 2

Supernatant MIF levels from fibroblast cell cultures (ng/2x10 5 cell). The samples were…

Figure 2
Supernatant MIF levels from fibroblast cell cultures (ng/2x105cell). The samples were obtained from five patients with dSSc and five healthy controls matched for age and sex. The concentration of MIF in patients with dSSc was significantly higher than in controls (p<0.01; Mann-Whitney rank sum test).

Figure 3

(A, B) Sclerodermal skin section…

Figure 3

(A, B) Sclerodermal skin section immunostained by anti-MIF antibody. (A) Positive basal and…

Figure 3
(A, B) Sclerodermal skin section immunostained by anti-MIF antibody. (A) Positive basal and suprabasal keratinocytes (arrow head). Original magnification x20. (B) Several positive perivascular mononuclear cells (arrow head). Original magnification x60. Antigen retrieval was carried out by incubating sections with the antihuman MIF goat polyclonal antibody diluted 1:300 in TBS. The reaction was shown using the streptavidin-biotin complex. (C) Negative control: SSc skin section immunostained by replacing the specific antibody with non-immune serum immunoglobulins at the same concentration as the primary antibody. Original magnification x20.
Figure 2
Figure 2
Supernatant MIF levels from fibroblast cell cultures (ng/2x105cell). The samples were obtained from five patients with dSSc and five healthy controls matched for age and sex. The concentration of MIF in patients with dSSc was significantly higher than in controls (p<0.01; Mann-Whitney rank sum test).
Figure 3
Figure 3
(A, B) Sclerodermal skin section immunostained by anti-MIF antibody. (A) Positive basal and suprabasal keratinocytes (arrow head). Original magnification x20. (B) Several positive perivascular mononuclear cells (arrow head). Original magnification x60. Antigen retrieval was carried out by incubating sections with the antihuman MIF goat polyclonal antibody diluted 1:300 in TBS. The reaction was shown using the streptavidin-biotin complex. (C) Negative control: SSc skin section immunostained by replacing the specific antibody with non-immune serum immunoglobulins at the same concentration as the primary antibody. Original magnification x20.

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