Tumor necrosis factor-α promoter polymorphism TNF2 is associated with a stronger delayed-type hypersensivity reaction in the skin of borderline tuberculoid leprosy patients

• Published in: Immunogenetics (New York) Vol. 53; no. 1; pp. 45 - 47
• Main Authors: Moraes, Milton O., Duppre, Nádia C., Suffys, Philip N., Santos, Adalberto R., Almeida, Alexandre S., Nery, José A. C., Sampaio, Elizabeth P., Sarno, Euzenir N.
• Format: Journal Article
• Language: English
• Published: 27.02.2001
• ISSN: 0093-7711; 1432-1211
• DOI: 10.1007/s002510000295

The Mitsuda test is a delayed-type hypersensitivity reaction against intradermically injected, heat-killed leprosy bacilli called lepromin. Inoculation of Mycobacterium leprae in situ induces the formation of gamma T-cell-mediated granulomas (Uyemura et al. 1991). A positive or negative response indicates resistance or susceptibility, respectively, to the lepromatous form of the disease (Ridley and Jopling 1996). Both environmental conditions (for example, exposure to the etiologic agent) and the immunogenetic background of the individual have been suggested to contribute to the development of the skin reaction (Feitosa et al. 1996). Tumor necrosis factor- alpha (TNF- alpha ) is a proinflammatory molecule that mediates expression of adhesion molecule and leukocyte migration into the skin (Groves et al. 1995). TNF- alpha plays a key role in the granulomatous response against mycobacteria (Aarestrup et al. 1995; Kindler et al. 1989). It is, therefore, plausible to suggest that TNF actively participates in the granulomatous response subsequent to the intradermal injection of lepromin. A TNF promoter polymorphism at position -308 (a G/A transition named TNF2) has been extensively associated with a variety of autoimmune and inflammatory disorders (Wilson et al. 1995). Although still somewhat controversial (Allen 1999), TNF2 is believed to affect promoter binding (Kroeger and Abraham 1996) and lead to increased mRNA expression (Kroeger et al. 1997) and protein secretion (Louis et al. 1998). TNF2 has also been shown to be associated with such inflammatory skin responses as irritant contact dermatitis (Allen et al. 2000). Furthermore, available data on the -308 polymorphism indicate that higher TNF- alpha levels can only be induced when certain cell types and stimuli are used (Kroeger et al. 2000). In view of these findings, this study investigated the correlation between the -308 TNF- alpha promoter polymorphic allele (TNF2 genotype) and the granulomatous response to lepromin in borderline tuberculoid (BT) leprosy patients.