1. Transglutaminases: the missing link in nephrogenic systemic fibrosis.
- Author
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Parsons AC, Yosipovitch G, Sheehan DJ, Sangüeza OP, Greenberg CS, and Sane DC
- Subjects
- Antigens, CD metabolism, Antigens, Differentiation, Myelomonocytic metabolism, Biopsy, Case-Control Studies, Contrast Media adverse effects, Factor XIIIa metabolism, Female, Fibroblasts enzymology, Fibroblasts pathology, Fibrosis chemically induced, Gadolinium adverse effects, Histiocytes enzymology, Histiocytes pathology, Humans, Male, Middle Aged, Skin Diseases chemically induced, Skin Diseases pathology, Syndrome, Renal Insufficiency enzymology, Skin enzymology, Skin pathology, Skin Diseases enzymology, Transglutaminases metabolism
- Abstract
Nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy (NFD), occurs in renal failure patients after gadolinium contrast exposure. The fibrosis of the dermis and subcutaneous septae accompanies fibrosis of other organs, including the heart, liver, lungs, and muscle. The fibrotic skin demonstrates increased dermal collagen, fibroblasts, and mucin. The mechanism by which gadolinium is associated with fibrosis is not known. We tested the hypothesis that upregulation of transglutaminases contributes to the fibrosis seen in the organs, including skin, of renal failure patients exposed to gadolinium contrast. We performed immunohistochemical studies using antibodies to transglutaminase-2, factor XIIIa, transglutaminase isopeptide, and the histiocyte marker CD68 on five archived skin biopsies of NSF. The results indicate that the dermal fibroblasts and histiocytes of NSF express transglutaminase-2, CD68, factor XIIIa, and transglutaminase isopeptide, indicating increased expression and/or activation of transglutaminases in NSF. We recommend further research into the use of transglutaminase inhibitors in the treatment and prevention of NSF.
- Published
- 2007
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