| Abstract: | Scabies, a parasitic skin infestation by the burrowing “itch” mite Sarcoptes scabiei, causes significant health problems for children and adults worldwide. Crusted scabies is a particularly severe form of scabies in which mites multiply into the millions, causing extensive skin crusting. The symptoms and signs of scabies suggest host immunity to the scabies mite, but the specific resistant response in humans remains largely uncharacterized. We used 4 scabies mite recombinant proteins with sequence homology to extensively studied house dust mite allergens to investigate a differential immune response between ordinary scabies and the debilitating crusted form of the disease. Subjects with either disease form showed serum IgE against recombinant S. scabiei cysteine and serine proteases and apolipoprotein, whereas naive subjects showed minimal IgE reactivity. Significantly (P < 0.05) greater serum IgE and IgG4 binding to mite apolipoprotein occurred in subjects with crusted scabies than in those with ordinary scabies. Both subject groups showed strong proliferative responses (peripheral blood mononuclear cells) to the scabies antigens, but the crusted scabies group showed increased secretion of the Th2 cytokines interleukin 5 (IL-5) and IL-13 and decreased Th1 cytokine gamma interferon (IFN-γ) in response to the active cysteine protease. These data confirm that a nonprotective allergic response occurs in the crusted disease form and demonstrate that clinical severity is associated with differences in the type and magnitude of the antibody and cellular responses to scabies proteins. A quantitative IgE inhibition assay identified IgE immunoreactivity of scabies mite antigens distinct from that of house dust mite antigens, which is potentially important for specific scabies diagnosis and therapy.Scabies is a disease of the skin caused by the burrowing “itch” mite Sarcoptes scabiei. The predominant disease manifestations are mediated through inflammatory and allergic-like reactions to mite products, leading to intensely pruritic skin lesions. A spectrum of disease is recognized, from the more common ordinary scabies (OS), with an average infestation of 10 to 15 mites per person, to a rare and severely debilitating form of the disease termed crusted (Norwegian) scabies (CS). In this form, mite infestations can number in the millions, and hyperkeratotic skin crusts develop (41, 50). Due to the extreme burden of mites, CS is considerably more infectious, and infectivity persists far longer, as eradicating mites from heavily crusted skin is extremely difficult.Crusted scabies is an important public health problem, not only for the individuals concerned, but also for their families and communities, in which sufferers may act as “core transmitters” who continue to reinfect others. In many remote Aboriginal communities in northern Australia, scabies prevalence is high: up to 65% in children, with first presentation peaking at 2 months of age (13).Adult female mites reside in burrows within the stratum granulosum of the epidermis. The clinical rash and itch present as papules or vesicles that may contain individual mites, eggs, egg cases, mite fecal pellets, and debris present in the burrow. A secondary, more generalized papular immune response also occurs. The associated underlying inflammatory response varies in intensity, with combinations of lymphocytes, histiocytes, and polymorphonuclear leukocytes (10, 47). Due to difficulties in isolating sarcoptic mites on the host in OS and to the clinical symptoms imitating those of other skin diseases, scabies is a challenging disease to diagnose (48). To date, limited investigations of humoral immunity to the scabies mite (SM) in patients have yielded contradictory results and have used scabietic extracts from other hosts, such as dogs (37). Interpretation of these studies is complex, as scabies mites are highly host specific and generally produce only a transient, self-limiting reaction in the nonpermissive host.In Darwin, Northern Territory, Australia, patients with CS were noted to have extremely high levels of total IgE and IgG in serum (41). Western blotting with plasma from these patients demonstrated that 6 of 7 individuals had strong IgE binding to S. scabiei var. canis protein extracts (2). Immunochemical studies have previously demonstrated that sera from rabbits infested with S. scabiei var. canis bind to house dust mite (HDM) extracts and, conversely, that sera from rabbits immunized with HDM extract bind with S. scabiei var. canis whole-mite protein extract (4-6, 18, 20, 36). Allergens from HDMs are recognized as major causes of allergic respiratory disease in humans (17, 43). As SMs and HDMs are phylogenetically related arthropods with similar nutritional requirements, it is not surprising that these mites or their excreta have homologous allergens. However, it is likely that only a few of these allergens are cross-reactive. For example, Der p 5 from the HDM Dermatophagoides pteronyssinus and Blo t 5 from the storage mite Blomia tropicalis have been studied extensively, and although they have 43% amino acid identity, they are not IgE cross-reactive (31). The identities of the specific cross-reactive molecules between S. scabiei and D. pteronyssinus remain undefined but may be glycan related (33).The recent development of S. scabiei cDNA libraries and expressed sequence tag (EST) databases (21, 29) allows more precise characterization of the specific antigens responsible for the immune reactions to the SM. The cDNAs encoding S. scabiei var. hominis cysteine proteases (27), serine proteases (26), glutathione S-transferase (GST) (16), and apolipoprotein (25) show homology to the D. pteronyssinus HDM group 1, 3, 8, and 14 allergens, respectively (43). As with HDMs, the availability of recombinant proteins and identification of key immunoreactive allergens for the SM would facilitate development of refined diagnosis and potential immunotherapy. Thus, more effective control of mite infestations at both an individual and a community level may be possible. We report here the characterization of specific antibody binding profiles and cellular immune responses of subjects with clinical scabies by using purified S. scabiei var. hominis recombinant proteins. Quantitative IgE inhibition analysis of cross-reactivity with HDM allergens identified IgE epitopes of scabies mite proteins distinct from HDM epitopes, a prerequisite for using purified allergens in scabies diagnosis and therapy. |
