Clinical and immunological features of patients with atopy and concomitant HTLV-1 infection.

Human T-cell lymphotropic virus type 1 (HTLV-1) induces an exacerbated type 1 immune response characterized by high spontaneous IFN-γ and TNF-α production. Allergic rhinitis and asthma are associated with the type 2 immune response, with elevated secretion of IL-4 and IL-5. The aim of this study was to characterize the immune response in atopic HTLV-1 carriers. The cytokine profile of atopic HTLV-1 carriers (N = 10; all females) was compared with that of non-atopic HTLV-1 carriers (N = 14; 9 females and 5 males). Mean patient age of atopic and non-atopic groups was 45 ± 8 and 38 ± 11 years, respectively. All atopic HTLV-1 carriers had rhinitis with or without asthma and a skin prick test positive for Dermatophagoides pteronyssinus antigen 1 (Derp-1). There was no difference in cytokine levels between the two groups in unstimulated peripheral blood mononuclear cell cultures. In cultures stimulated with Derp-1, IFN-γ levels tended to be higher (P = 0.06) and IL-5 levels were higher (P = 0.02) in atopic HTLV-1 patients than in non-atopic subjects. In contrast, IL-10 was lower (P = 0.004) in atopic than in non-atopic HTLV-1-infected subjects. This study shows that HTLV-1 infection with an exaggerated type 1 immune response does not prevent atopy. In this case, the exacerbated type 1 and type 2 immune responses were due to a lack of IL-10 production, a cytokine that plays an important role in down-modulating type 1 and type 2 immune responses and in preventing the development of chronic inflammatory diseases.

Clinical and immunological features of patients with atopy and concomitant HTLV-1 infection

Human T-cell lymphotropic virus type 1 (HTLV-1) induces an exacerbated type 1 immune response characterized by high spontaneous IFN-γ and TNF-α production. Allergic rhinitis and asthma are associated with the type 2 immune response, with elevated secretion of IL-4 and IL-5. The aim of this study was to characterize the immune response in atopic HTLV-1 carriers. The cytokine profile of atopic HTLV-1 carriers (N = 10; all females) was compared with that of non-atopic HTLV-1 carriers (N = 14; 9 females and 5 males). Mean patient age of atopic and non-atopic groups was 45 ± 8 and 38 ± 11 years, respectively. All atopic HTLV-1 carriers had rhinitis with or without asthma and a skin prick test positive for Dermatophagoides pteronyssinus antigen 1 (Derp-1). There was no difference in cytokine levels between the two groups in unstimulated peripheral blood mononuclear cell cultures. In cultures stimulated with Derp-1, IFN-γ levels tended to be higher (P = 0.06) and IL-5 levels were higher (P = 0.02) in atopic HTLV-1 patients than in non-atopic subjects. In contrast, IL-10 was lower (P = 0.004) in atopic than in non-atopic HTLV-1-infected subjects. This study shows that HTLV-1 infection with an exaggerated type 1 immune response does not prevent atopy. In this case, the exacerbated type 1 and type 2 immune responses were due to a lack of IL-10 production, a cytokine that plays an important role in down-modulating type 1 and type 2 immune responses and in preventing the development of chronic inflammatory diseases.

Recombinant leishmania antigens for serodiagnosis of visceral leishmaniasis.

Serological tests with crude or recombinant Leishmania antigens are important tools for the diagnosis of leishmania infection. However, these tests are not markers of active visceral leishmaniasis (VL), since antibodies to these markers are often observed in individuals with subclinical L. chagasi infection and they do not fall shortly after therapy. In this study, levels of immunoglobulin G (IgG) against three recombinant Leishmania antigens (rH2A, KMP11, and the "Q" protein) were evaluated in sera from individuals with subclinical L. chagasi infection and in patients with VL pre- and posttherapy. The sensitivity of the serological test for diagnosis of VL was 100% with all three antigens. The titers of IgG fell significantly after therapy. While most of the individuals with subclinical L. chagasi infection had antibodies to rH2A and the "Q" protein, only 1 out of 15 individuals had antibodies to KMP11. These data indicate that KMP11 may be used to discriminate L. chagasi infection from active VL and may serve as a marker of response to therapy.

Antileishmanial IgG and IgE antibodies recognize predominantly carbohydrate epitopes of glycosylated antigens in visceral leishmaniasis.

The specificity of human antileishmanial IgG and IgE antibodies to glycosylated antigens of Leishmania chagasi was evaluated. An ELISA was performed with soluble leishmanial antigen (SLA) and a panel of 95 sera including samples from patients with subclinical infection (SC) and visceral leishmaniasis (VL), subjects cured of visceral leishmaniasis (CVL), and from healthy individuals from endemic areas (HIEA). Antileishmanial IgG were verified for 18 (40%) of 45 SC subjects (mean absorbance of 0.49 +/- 0.17). All nine sera from VL patients had such antibody (0.99 +/- 0.21), while 11 (65%) of 17 CVL individuals were seropositive (0.46 +/- 0.05). Only three (12%) of 24 HIEA controls reacted in IgG-ELISA. Antileishmanial IgE was detected in 26 (58%) of 45 SC patients (0.35 +/- 0.14), and in all VL patients (0.65 +/- 0.29). These antibodies were also detected in 13(76%) of 17 CVL subjects (0.42 +/- 0.14) while all HIEA controls were seronegative. There was no correlation between antileishmanial IgG and IgE antibody absorbances. Mild periodate oxidation at acid pH of SLA carbohydrates drastically diminished its antigenicity in both IgG and IgE-ELISA, affecting mainly the antigens of 125, 102, 94, and 63 kDa as demonstrated by western immunoblotting.

Antileishmanial IgG and IgE antibodies recognize predominantly carbohydrate epitopes of glycosylated antigens in visceral leishmaniasis

The specificity of human antileishmanial IgG and IgE antibodies to glycosylated antigens of Leishmania chagasi was evaluated. An ELISA was performed with soluble leishmanial antigen (SLA) and a panel of 95 sera including samples from patients with subclinical infection (SC) and visceral leishmaniasis (VL), subjects cured of visceral leishmaniasis (CVL), and from healthy individuals from endemic areas (HIEA). Antileishmanial IgG were verified for 18 (40 percent) of 45 SC subjects (mean absorbance of 0.49 ± 0.17). All nine sera from VL patients had such antibody (0.99 ± 0.21), while 11 (65 percent) of 17 CVL individuals were seropositive (0.46 ± 0.05). Only three (12 percent) of 24 HIEA controls reacted in IgG-ELISA. Antileishmanial IgE was detected in 26 (58 percent) of 45 SC patients (0.35 ± 0.14), and in all VL patients (0.65 ± 0.29). These antibodies were also detected in 13(76 percent) of 17 CVL subjects (0.42 ± 0.14) while all HIEA controls were seronegative. There was no correlation between antileishmanial IgG and IgE antibody absorbances. Mild periodate oxidation at acid pH of SLA carbohydrates drastically diminished its antigenicity in both IgG and IgE-ELISA, affecting mainly the antigens of 125, 102, 94, and 63 kDa as demonstrated by western immunoblotting.

Influence of human T-cell lymphocytotropic virus type 1 infection on serologic and skin tests for strongyloidiasis.

The aim of this study was to determine whether human T-cell lymphocytotropic virus type 1 (HTLV-1) infection may affect the levels of parasite-specific immunoglobulin (Ig) G and IgE and the positivity of the skin test for strongyloidiasis. Participants included 67 patients with strongyloidiasis (40 without HTLV-1 infection and 27 coinfected with HTLV-1). We determined IgG and IgE levels by enzyme-linked immunosorbent assay, and the immediate hypersensitivity skin test was performed with the metabolic Strongyloides stercoralis antigen. Specific IgE levels and the size of skin reactions in patients without HTLV-1 were higher (P < 0.01) than those observed in patients coinfected with HTLV-1. Additionally, 89% of patients without HTLV-1 had specific IgE and 92.5% had positive skin tests; however, these values were significantly reduced (P < 0.01) in patients coinfected with HTLV-1 (44% and 59%, respectively). These data show that HTLV-1 infection decreases the sensitivity of detection of S. stercoralis-specific IgE, the size of the immediate hypersensitivity reaction, and the sensitivity of these tests in the diagnosis of strongyloidiasis.

Nature and incidence of erythrocyte-bound IgG and some aspects of the physiopathogenesis of anaemia in American visceral leishmaniasis.

IgG molecules were found associated with erythrocyte membranes in all patients with American visceral leishmaniasis. They were detected by two different immunoradiometric assays and by one enzyme-linked immunosorbent assay. Although autoimmune phenomena seem to be constant features of American visceral leishmaniasis, the erythrocyte-bound IgG are not erythrocyte-specific autoantibodies. Moreover, anti-Leishmania activity was found associated with the erythrocyte-bound IgG, indicating that the IgG may be a component of Leishmania antigens-anti-Leishmania immune complexes. No associations were found between the amounts of erythrocyte-bound IgG and the degree of anaemia or between spleen dimensions and the degree of anaemia. These findings suggest that the pathogenesis of anaemia in American visceral leishmaniasis is multifactorial.

Evaluation of the micro enzyme-linked immunosorbent assay (ELISA) for antibodies in American visceral leishmaniasis: antigen selection for detection of infection-specific responses.

This study was designed to evaluate the ELISA for diagnosis of American visceral leishmaniasis (AVL) using antigen prepared from different Leishmania isolates and from a strain of Trypanosoma cruzi. Two Leishmania donovani chagasi isolates from Bahia and Maranhão (both states of northern Brazil), one L. donovani from Sudan, one L. mexicana amazonensis isolate, and one T. cruzi isolate were used. A total of 375 sera were tested, including 119 from AVL patients, 96 from nonleishmaniasis hospitalized patients, 20 from healthy persons, 30 from patients with mucocutaneous leishmaniasis, 28 from patients with Chagas' disease, 20 from patients with tuberculosis, 21 from leprosy patients, 27 from schistosomiasis patients and 14 from patients with systemic mycoses. The antigens prepared from L. d. chagasi (Bahia) and L. m. amazonensis showed the highest sensitivity (98% and 99%, respectively) for detecting antibodies in sera from AVL patients. However, the specificity of L. d. chagasi (Bahia) antigen was better than that of L. m. amazonensis (96% vs. 86%). Comparison among the three L. donovani isolates demonstrated that the antigen prepared with the isolate from the same area where the sera originated yielded higher mean absorbance than the others. By using spectrophotometric absorbance values it was possible to use a single dilution of serum (between 1/100-1/400) since a clear separation was seen between AVL patients and controls. No patients with the other diseases who were tested gave positive results. We suggest that ELISA can be a very convenient, sensitive, and specific test for diagnosis of AVL when soluble antigen, preferably from an isolate from the test area, is used.