Epithelial hyperproliferation and transglutaminase 1 gene expression in Stevens-Johnson syndrome conjunctiva

In Stevens-Johnson syndrome, pathological keratinization of the ordinarily nonkeratinized corneal and conjunctival mucosal epithelia results in severe visual loss. We examined conjunctiva covering cornea in five eyes in the c hronic cicatricial phase of Stevens-Johnson syndrome. Normal conjunctiva fr om five age-matched individuals was studied also. The number of epithelial cells in Stevens-Johnson syndrome conjunctiva that were immunoreactive with a monoclonal antibody, Ki-67, to a nuclear antigen found only in prolifera ting cells was greater than normal (93.8 +/- 19.8 cells above 100 basal cel ls versus 12.8 +/- 0.5 cells above 100 basal cells; P = 0.009). In addition , although clinical inflammation was mild, massive lymphocytic infiltration was seen in the substantia propria of conjunctiva covering cornea In situ hybridization documented transglutaminase 1 (keratinocyte transglutaminase) mRNA in suprabasal cells of the abnormally thickened conjunctival epitheli um in all Stevens-Johnson syndrome patients. In contrast, no message was de tected in normal conjunctival or corneal epithelia. Transglutaminase 1 is e xpressed during the terminal differentiation of keratinocytes where it help s synthesize cornified cell envelopes. We speculate that in Stevens-Johnson syndrome, epithelial hyperproliferation, and transglutaminase 1 gene expre ssion lead to the pathological keratinization of ocular surface mucosal epi thelia.