Immune response to sulfamethoxazole in patients with AIDS

Abstract

Antibody-and cell-mediated responses to sulfamethoxazole (SMX) were analyzed in AIDS patients with or without a history of hypersensitivity and in negative controls. In 20 of 20 (P < 0.01) human immunodeficiency virus (HIV)-seropositive patients with skin reactions to cotrimoxazole, we found SMX-specific antibodies, while only 9 of 20 and 17 of 20 HIV-seropositive patients without a history of hypersensitivity to cotrimoxazole had SMX-specific immunoglobulin M (IgM) and IgG, respectively. The levels of specific IgM and IgG were higher in patients with skin reactions than in patients without reactions (IgM, 1.0 ؎ 0.19 versus 0.47 ؎ 0.23 [P < 0.001]; IgG, 0.68 ؎ 0.15 versus 0.47 ؎ 0.14 [P < 0.001] [mean optical density values ؎ standard deviations]). Seronegative controls with no history of exposure to sulfa compounds did not have SMX-specific IgG or IgM antibodies, and controls with a history of intake of SMX with or without reactions had low levels of IgG and IgM. The SMX-specific IgG subclasses were exclusively IgG1 and IgG3. None of the patients had detectable SMX-specific IgE or IgA antibodies nor did they exhibit a cell-mediated response as measured by a lymphocyte proliferation assay. Antibodies to SMX recognized N-acetyl-sulfonamide, N-(2-thiazolyl)-sulfanilamide, sulfadiazine, and sulfisoxazole but did not recognize sulfanilamide or 3-amino-5-methyl isoxazole in an inhibition assay. It is not known whether the SMX-specific antibodies associated with hypersensitivity reactions to SMX in HIV-seropositive patients have a pathogenic role in these reactions. Sulfanilamide or 3-amino-5-methyl isoxazole, on the other hand, could be potential alternative therapies in HIV-seropositive patients with a history of skin reactions to SMX.

Clinical Findings in 40 Dogs with Hypersensitivity Associated with Administration of Potentiated Sulfonamides

“…The delay of 5 or more days from drug exposure to adverse reaction is similar to the time required for humoral or delayed type IV hypersensitivity responses. In humans with sulfonamide hypersensitivity, antibodies to platelets, 14 hepatic microsomal proteins, 15 and sulfamethoxazole itself, 16 as well as T cells sensitized to sulfonamides and their metabolites, 17 have been identified. In one dog with erythema multiforme, antibodies to dermal components were identified.…”

Delayed hypersensitivity reactions to sulphonamides: syndromes, pathogenesis and management

“…The time course of the reactions, with an onset of clinical signs seven or more days after drug initiation, is suggestive of a humorally mediated reaction. In support of this, circulating drug‐dependent IgG and IgM have been documented in human patients with the delayed form of sulphonamide hypersensitivity 59 –61 . Immediate type hypersensitivity reactions to sulphonamides, involving urticaria or bronchspasm, have also been documented in humans, but these reactions appear to be different in their pathogenesis in that sulfamethoxazole‐reactive IgE, not IgG, has been identified 62 .…”

Idiosyncratic toxicity associated with potentiated sulfonamides in the dog

“…The prevailing hypothesis regarding the pathogenesis of sulfonamide hypersensitivity is that the parent sulfonamide is bioactivated to reactive metabolites, which haptenize tissue proteins, leading to antigen presentation and T-cell proliferation. There is some evidence for humoral involvement in sulfonamide hypersensitivity, in that human patients with hypersensitivity have been shown to have antibodies that recognize native hepatic microsomal proteins , platelet proteins (Kiefel et al, 1987;Curtis et al, 1994), or SMX itself (Daftarian et al, 1995). However, anti-drug antibodies are neither sensitive nor specific for these reactions, as they are absent in many hypersensitive patients (Gruchalla et al, 1998), and may be present in patients who are tolerant to sulfonamides (Daftarian et al, 1995).…”