The treatment of mastocytoma cells with 8-methoxypsoralen and long-wavelength ultraviolet radiation enhances cellular immunogenicity: preliminary results.

Evidence for the increased immunogenicity of mastocytoma cells (P815) treated with 8-methoxypsoralen (8-MOP) and long-wavelength ultraviolet radiation (UVA) is presented. A highly tumorigenic clone (P1) became much less tumorigenic (tum-) after repetitive phototreatments with 8-MOP (16 ng/mL) and UVA (1 J/cm2). The yield of tum- clones was proportional to the number of phototreatments. In a pilot study in which P1 cells were treated with three successive rounds of 8-MOP/UVA, one clone out of 73 was tum-. In a second series of experiments, the P1 cells were treated 10 times and 4 out of 100 clones were much less tumorigenic. When some of the tum- clones were administered intraperitoneally to DBA/2 mice, significant protection against challenge with the original P1 clone was observed. In addition, the transfer of immune cells from tum(-)-treated mice allowed the transfer of resistance to other tum- clones to immunosuppressed mice (650 rad). These results are consistent with earlier literature showing the potent mutagen, N-methyl-N'-nitrosoguanidine, led to mutations in P1 that altered the expression of new surface antigens, which stimulated the murine immune system such that there was also cross recognition of shared antigens on untreated P1 cells used to challenge the immunized mice. The increased immunogenicity that resulted from the less mutagenic 8-MOP/UVA treatment may arise by a similar mechanism and may be responsible in part for the efficacy of 8-MOP/UVA photochemotherapy for the treatment of cutaneous T cell lymphoma.

Diagnosis of Lyme disease based on dermatologic manifestations.

Lyme disease, or Lyme borreliosis, is an infection caused by the spirochete Borrelia burgdorferi, which is most commonly transmitted to humans by a tick bite. Characterized by early and late phases, Lyme disease is a multisystem illness involving the skin, heart, joints, and nervous system. Diagnosis is based predominantly on clinical manifestations, the most specific being dermatologic. Thus, recognizing the dermatologic manifestations of Lyme disease is important for diagnosis and institution of appropriate, effective therapy. Approximately 75% of patients with Lyme disease present with the pathognomonic skin lesion erythema migrans, an expanding erythematous lesion. During early infection, secondary erythema migrans lesions or Borrelia lymphocytoma may occur. Borrelia lymphocytoma commonly presents as an erythematous nodule on the ear lobe or nipple. During late infection, acrodermatitis chronica atrophicans, an erythematous, atrophic plaque unique to Lyme disease may appear; it has been described in about 10% of patients with Lyme disease in Europe. Fibrotic nodules associated with acrodermatitis chronica atrophicans as well as other sclerotic and atrophic lesions, such as morphea, lichen sclerosus et atrophicus, anetoderma, and atrophoderma of Pasini and Pierini, have been seen late in the course of Lyme disease. In a few cases, other sclerodermatous lesions, such as eosinophilic fasciitis and progressive facial hemiatrophy, have been linked to B. burgdorferi infection. We review the cutaneous lesions associated with Lyme disease.

Monoclonal antibodies to parasite antigens found in the serum of Dirofilaria immitis-infected dogs.

We recently reported that parasite antigens are detectable in the serum of Dirofilaria immitis-infected dogs by counterimmunoelectrophoresis (CIE). Hybridoma cell lines that produce monoclonal antibodies specific for these antigens were obtained by immunizing mice with a partially purified antigen preparation, fusing spleen cells with SP-2 myeloma cells, and screening cell culture supernatants for antibody by ELISA and CIE inhibition. Antibodies specific for two epitopes shared by the two major circulating parasite antigens were identified. Immunoperoxidase studies showed that the epitopes recognized by the monoclonals were widely distributed in D. immitis, but the female uterus and eggs were particularly strongly labeled. A monoclonal antibody-based ELISA was developed to measure parasite antigens in dog sera. Parasite antigens were detected in 45 of 46 sera from infected dogs but were absent in sera from uninfected dogs and sera from dogs infected with Dipetalonema reconditum. Serum antigen content was significantly correlated with the number of female worms recovered from infected dogs (r = 0.82, p less than 0.001). Antigenemia was first detected 6 mo after infection, and antigen levels remained fairly stable between 9 and 21 mo after infection. Parasite antigen detection with this monoclonal antibody-based ELISA appears to be superior to previously described diagnostic methods for canine dirofilariasis in terms of sensitivity, specificity, and relation to infection intensity.

Detection of circulating parasite antigens in canine dirofilariasis by counterimmunoelectrophoresis.

Circulating Dirofilaria immitis antigen was detected in sera from 24 of 24 infected dogs by counterimmunoelectrophoresis (CIE). Parasite antigen was not detected in sera from uninfected dogs or dogs with Dipetalonema reconditum infection. In experimentally infected dogs, the antigen was first detectable 6.5-8.5 months after infection. Preliminary evidence suggests that the antigen is present in male and female adult worms but not in microfilariae. Sera from dogs with microfilaremic and amicrofilaremic infections contained statistically equivalent amounts of D. immitis antigen. However, a significant correlation was observed between serum parasite antigen content and the number of adult worms present in individual dogs at necropsy. Previous studies from several laboratories have shown that microfilarial counts and serum antibody titers are not related to adult worm counts in canine dirofilariasis or other filarial infections. Thus, CIE detection of D. immitis antigenemia represents a significant improvement over previously available diagnostic techniques because it is more sensitive than microfilarial tests, more specific than antibody tests, and the only test that has been related to infection intensity.