Tumor necrosis factor alpha (TNF-␣) may play a central role in the disease pathogenesis which occurs as a consequence of chlamydial infection. To investigate the importance of TNF-␣ gene promoter polymorphisms and TNF-␣ levels in tear fluid in scarring trachoma, a large matched-pair case-control study was performed in The Gambia. The-308A allele was present in a higher proportion of patients (28.4%) than controls (18.4%), with an increasing association for homozygotes (2 for trend, P ‫؍‬ 0.032; allele frequency, 0.163 in patients and 0.099 in controls; 2 , P ‫؍‬ 0.025). For the-238A allele, the association was similar but not significant. The disease association was highly significant when the number of either-308A or-238A sites in an individual was considered (P ‫؍‬ 0.003). TNF-␣ promoter alleles are tightly linked to some HLA class I and II alleles, but multivariate analysis confirmed that the disease associations were independent of HLA, although a class I allele, A*6802, is also associated with disease. TNF-␣ was more frequently detected in tear samples from patients (27.6%) than from controls (15.9%), increasingly so for higher levels of detectable TNF-␣ (P ‫؍‬ 0.015). Among patients, detectable TNF-␣ in tears was highly associated with the presence of ocular chlamydial infection (P < 0.001). The results indicate that TNF-␣ plays a major role in the tissue damage and scarring which occurs as a consequence of Chlamydia trachomatis infection.

To determine if serum antibody response to the 60-kDa chlamydial heat-shock protein (Chsp60) was associated with scarring trachoma, responses to Chlamydia trachomatis and to Chsp60 from 148 Gambian subjects with trachomatous scarring and from 148 controls without clinical evidence of disease from trachoma-endemic communities were characterized. Chsp60 response was found in 32% of cases and 16% of controls (P < .001). Although C. trachomatis titer was also higher in cases than controls, the prevalence of Chsp60 response between the 2 groups remained significantly different after stratifying for C. trachomatis titer (weighted odds ratio [OR] = 2.1, P = .02). Chsp60 response and C. trachomatis serovar A titer of > or =128 were independently associated with scarring trachoma. The presence of HLA class II allele DRB1*0701 was positively correlated with Chsp60 response (OR = 2.6, P = .02), and DQB1*0301 and DQB1*0501 were negatively associated (OR = 0.42, P < .001; OR = 0.55, P = .46, respectively).

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