Definition of a Trichophyton protein associated with delayed hypersensitivity in humans. Evidence for immediate (IgE and IgG4) and delayed hypersensitivity to a single protein.

Dermatophytes of the genus Trichophyton cause infections of human skin, nails, and hair. Unlike most Ags, Trichophyton can elicit either immediate (IH) or delayed (DH) hypersensitivity skin reactions. Previous studies isolated a 30-kDa Ag (Tri t 1) that caused IH skin tests. The study presented here used skin testing and in vitro T cell proliferation assays to monitor purification of an Ag, designated Protein IV, associated with DH reactions. Protein IV was purified by cation exchange HPLC; amino acid sequence analysis of the N-terminus and nine internal peptides (143 residues) revealed no homologies to Tri t 1 or to any other known proteins. A mAb-based ELISA was developed to measure Protein IV. Protein IV elicited DH skin reactions in subjects with a history of athlete's foot but also caused IH skin reactions. Serologic responses to Protein IV were studied in 59 adults who had been skin tested with Trichophyton extract. IH skin reactions were associated with a positive RAST (14/23) as well as with specific IgE (13/23) and IgG4 (14/23) Abs to Protein IV. DH skin tests were not associated with IgE or IgG4 Abs. IgE anti-Protein IV Abs were quantitatively correlated with IgG4 Abs (r = 0.57, p < 0.001). Specific IgG Abs to Protein IV were highest in IH subjects (gm = 230 U/ml), and lowest in those with DH (gm = 91 U/ml) or negative (gm = 81 U/ml) skin tests; furthermore, the prevalence of IgG Abs increased significantly with age. Protein IV is the first defined protein associated with both DH and IH skin reactions; these reactions are characterized by distinct serologic responses. The results establish that diverse immune responses in humans can be directed against the same protein.

Atopic dermatitis associated with dermatophyte infection and Trichophyton hypersensitivity.

An atopic patient with tinea unguium, immediate hypersensitivity to Trichophyton, and elevated specific IgE antibody to Trichophyton had recalcitrant hand and foot eczema that resolved following the administration of systemic antifungal therapy for her tinea unguium. The patient fulfills criteria for the atopic-chronic-dermatophytosis syndrome described by Jones. The authors suggest that the patient's atopic dermatitis may have been exacerbated by her chronic dermatophyte infection and Trichophyton hypersensitivity.

Trichophyton tonsurans allergen. I. Characterization of a protein that causes immediate but not delayed hypersensitivity.

Fungal infections of skin or nails are extremely common and often caused by dermatophyte fungi of the genus Trichophyton. These fungi are unusual in that they can give rise to delayed hypersensitivity (DH) or immediate hypersensitivity (IH) responses. Recently, IH to Trichophyton tonsurans has been demonstrated in patients by skin tests, serum IgE antibody test (RAST), and positive nasal and bronchial challenges. To further investigate the immunology of Trichophyton, a 30-kDa T. tonsurans allergen was isolated by gel filtration and hydrophobic interaction chromatography. This protein, Tri t I, gave a single band on SDS-PAGE, and the 30 amino-terminal amino acids have been determined. Among patients with positive IH skin tests, 34 of 48 (71%) had IgG antibody and 26 of 48 (54%) had IgE antibody to Tri t I. Among those who had positive responses to both skin tests and RAST, 22 of 30 (73%) had IgE antibodies to Tri t I; thus, this protein represents a major allergen. Twelve clones of murine IgG mAb antibodies were produced. Two clones, 2F2-F7 and 6B11-C2, were found to define separate epitopes on Tri t I and were used to develop an immunometric assay for the quantitation of Tri t I. Twenty-three of 38 volunteers with a history of athlete's foot were found to have either IH and/or DH to Trichophyton mix and underwent further testing with purified Tri t I. Of the nine found to have IH to the mix, eight were sensitive to Tri t I. Seven of these eight had IgG and IgE antibodies to Tri t I, by Ag-binding RIA, and all were RAST positive to the unpurified extract. An additional 14 had either DH alone (n = 7) or a wheal and flare response followed by DH at 48 h (n = 7). Of these 14 who had DH responses to Trichophyton mix, only one showed DH to an equivalent quantity of purified Tri t I; among this group, none showed IH or serum IgE antibodies and only one had detectable IgG antibody to Tri t I. The results suggest that the majority of subjects with DH to Trichophyton are responding to a protein other than Tri t I and that the wheal that precedes DH reactions is some patients is not associated with IgE antibodies.