Immunopathogenesis of conjunctival scarring in trachoma.

PURPOSE

Trachoma, a chronic follicular conjunctivitis caused by infection with Chlamydia trachomatis, is the leading cause of preventable blindness. The blinding complications are associated with progressive conjunctival scarring that may result from immunologically mediated responses. We studied the processes involved in the regulation of inflammation and fibrosis in trachoma by investigating the expression of fibrogenic cytokines in the conjunctiva.

METHODS

We studied conjunctival biopsy specimens obtained from nine subjects with active trachoma and from four control subjects. We used immunohistochemical techniques and a panel of monoclonal and polyclonal antibodies directed against interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) and platelet-derived growth factor (PDGF). In addition, we characterised the composition of the inflammatory infiltrate by the use of a panel of monoclonal antibodies. Sirius red and Van Gieson stains were used to characterise the extent of fibrous tissue in the substantia propria.

RESULTS

Trachoma specimens showed greater numbers of inflammatory cells than control specimens. The expression of cytokines was absent in the normal conjunctiva. Cytoplasmic IL-1 alpha and IL-1 beta expression was noted in the conjunctival epithelium in all trachoma specimens. IL-1 alpha, IL-1 beta, TNF-alpha and PDGF were detected in macrophages infiltrating the substantia propria. B lymphocytes predominated over T lymphocytes in six trachoma biopsies with fibrosis confined to the deep substantia propria, whereas T lymphocytes predominated over B lymphocytes in three biopsies with more extensive fibrosis. In all trachoma biopsies helper/inducer T lymphocytes outnumbered suppressor/cytotoxic T lymphocytes.

CONCLUSIONS

The upregulated local production of IL-1 alpha, IL-beta, TNF-alpha and PDGF might contribute to conjunctival damage and scarring in trachoma.