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Abstract Vitiligo is an acquired depigmenting disorder characterized by the loss of melanocytes from the epidermis and it affected between 1% and 2% of the general population without any racial, sexual or regional differences. Vitiliginous patches contain either reduced melanin or no pigment at all. The patches are initially small but they progressively enlarge and coalesce into larger patches. The pathogenesis of vitiligo is attributable to many hypotheses that have been proposed to explain the destruction of melanocytes, including neurogenic theory, the self-destructive theory and the autoimmune theory. Stressed cells are characterized by elevated expression of stress proteins. Stress proteins include the heat shock protein (Hsp) family which is upregulated in response to elevated environmental temperatures and other forms of stresses. Stress proteins are immunogenic and were shown to serve as antigens in certain autoimmune diseases. Stress proteins also enhance an immune response by inducing phagocytosis and processing of chaperoned antigens by dendritic cells. The objective of this study was to investigate Hsp70 expression in skin of normal individuals compared to vitiligo patients and to correlate this expression with the clinicopathological parameters of the latter group, to explore the possible role of Hsp70 in the pathogenesis of this disease. This study was carried out on thirty two patients with vitiligo and ten healthy volunteers as controls. Skin biopsies were taken; histopathological evaluation using hematoxylin and eosin staining, and immunohistochemical evaluation of Hsp 70 using mouse monocolonal antibody were performed. Histopathological examination of the vitiliginous biopsies revealed many changes such as keratinocytes vacuolization, basement membrane thickening and dermal perivascular inflammatory infiltrate. Complete absence of melanin was observed in most of the cases (65.6%). Perilesional skin showed also some features that precede the occurrence of vitiligo like keratinocytes vacuolization, and presence of dermal inflammation but they retain significant amount of melanin. As regards, Hsp70 expression, all normal skin showed positivity for Hsp70 with cytoplasmic localization while 96.9% of vitiligo cases showed Hsp70 expression with nucleocytoplasmic pattern in 64.5% of cases and cytoplasmic pattern in 35.5% of cases. The percentage of Hsp 70 expression in vitiliginous skin ranged between 0 –100, with a mean of 68.59±29.27 and a median of 75 while H score of Hsp 70 expression in those lesions ranged between 0 and 300 with a mean of 158.28±89.96 and a median of 150. Vitiligo skin showed more intense expression compared to control skin (p<0.001). Nucleocytoplasmic pattern was only seen in vitiligo skin in comparison with normal skin that showed cytoplasmic pattern only (p<0.001). The median value of percentage (p<0.001) and H score of Hsp70 expression (p<0.001) were higher in vitiligo skin compared to normal skin. Nucleocytoplasmic pattern of Hsp70 tended to be associated with progressive increase in severity of disease assessed by VIDA score (p=0.07). The median value of Hsp70 percentage of expression tended to be higher in patients with short disease duration in comparison with those with prolonged diseases (p=0.08) Hsp70 was studied in the three perilesional biopsies which revealed positive expression with a cytoplasmic pattern in 2 cases and nucleocytoplasmic pattern in one case. It was expressed in a mild intensites in 2 cases (66.7%) and strong intensity in one case (33.3%). The percentage of Hsp 70 expression in perilesional biopsy ranged between 10 – 90, with a mean of 36.66± 46.18 and a median of 10.0 while H score of Hsp 70 expression ranged between10 and 270 with a mean of 96.66 ±150.11and a median of 10. Hsp70 was also reported to be increased in other skin diseases compared to normal skin such as psoriasis suggesting its role in the pathogenesis of psoriasis Hsp70 was also described to be expressed in lichen planus and systemic sclerosis. from the present study, up-regulation of heat shock protein 70, in the form of its intense and diffuse expression may be blamed in pathogenesis of vitiligo. Nuclear localization of heat shock protein 70 may be more important than its presence or absence, beside it may be related to progression of the disease. |