bromochloroacetic-acid and Leprosy

Cryostat sections of full-thickness skin biopsies from 21 patients along the whole spectrum of leprosy were subjected to immunohistological examination with special regard to defective lymphokine production. There was an inverse relationship between intra-lesional IL-1 reactivity and IL-2R expression, in that the latter was markedly observed in tuberculoid lesions. Whenever epithelioid cell containing granulomas were present in paucibacillary forms, significant reactivity within the central phagocytic cells with the monoclonal antibody directed against interferon-gamma was detectable. The keratinocytes covering tuberculoid lesions abundantly expressed class II alloantigens (HLA-DR antigens), indicating high intra-lesional interferon-gamma activity. In contrast, multibacillary forms revealed significant anti-IL-1 reactivity within the cellular infiltrate. IL-2R bearing cells were virtually absent as was anti-HLA-DR reactivity of the keratinocytes, underlining a defective intra-lesional interferon-gamma activity.

Topics: Epidermal Cells; HLA-DR Antigens; Humans; Interferon-gamma; Interleukin-1; Interleukin-2; Keratins; Leprosy; Macrophages; Receptors, Antigen, T-Cell; Receptors, Immunologic; Receptors, Interleukin-2; Skin

Sera from 34 patients with lepromatous leprosy were screened for the presence of autoantibodies by indirect immunofluorescence using two epithelial cell lines, PTK2 and HEp2, as substrates. Indirect immunofluorescence staining of both substrates with the serum of a patient with lepromatous leprosy revealed a cytoplasmic intermediate filament staining pattern. After exposure of PTK2 cells to colchicine, the filaments collapsed into thick perinuclear coils, confirming the presence of intermediate filament reactivity. Immunofluorescence of rat fibroblasts with the same serum also revealed an intermediate filamentous staining pattern. Human keratinocytes exposed to the patient's serum revealed a diffuse cytoplasmic staining pattern. Our study suggests the presence of autoantibodies to cytoskeletal intermediate filaments or to molecules associated with vimentin and possibly keratin subunit proteins in the serum of a patient with lepromatous leprosy.

Topics: Adult; Autoantibodies; Cells, Cultured; Colchicine; Cytoskeleton; Female; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Leprosy; Vimentin

Significant epidermal changes were observed in lesions of leprosy patients undergoing type 1 (reversal) and type 2 (erythema nodosum leprosum, ENL) reactions. Using indirect immunofluorescence and frozen sections stained with the appropriate monoclonal antibodies, an increase in epidermal cell layers, the presence of Ia on keratinocytes, an increase in Langerhans' cell numbers, and scattered T cells within the epidermis were seen in both types of reactions. Although borderline tuberculoid patients with type 1 reactions showed the consistent presence of Ia on all keratinocytes, lepromatous patients undergoing ENL reactions showed only a patchy distribution. Taken together, these studies indicate that local T-cell activation leading to the production of terminal lymphokine, such as interferon-gamma, with subsequent induction of Ia on epidermal cells may be an important event in reactional leprosy states. It is of interest that the hitherto considered "anergic" lepromatous patients should recover temporary T-cell reactivity during the natural course of the disease.

Topics: Antibodies, Monoclonal; Cell Count; Epidermis; Fluorescent Antibody Technique; Frozen Sections; Histocompatibility Antigens Class II; Humans; Immunity, Cellular; Keratins; Langerhans Cells; Leprosy; T-Lymphocytes

Our knowledge of the induction of new molecules by IFN-gamma has led to the characterization of IP-10 and the preparation of a monospecific, polyclonal antibody. Using this reagent we have now examined inflammatory states occurring in human skin and used immunocytochemical staining for the expression of both Ia and IP-10 determinants. After evoking a delayed-type response to purified protein derivative of tuberculin (PPD), we noted the presence of IP-10 in dermal macrophages and endothelial cells. Intense staining of the basal layer of epidermal keratinocytes was prominent at 41 h, and by 1 wk the entire epidermis was staining. The comparison of the amount of IP-10 secreted by keratinocytes vs. macrophages, fibroblasts, and endothelial cells revealed that keratinocytes were by far the major producers of this molecule. The expression of Ia occurred in conjunction with IP-10. The injection of rIFN-gamma mimicked many of the features of the PPD response, including the expression of both Ia and IP-10 by epidermal keratinocytes. Coexpression was also found in the natural lesions of tuberculoid leprosy and cutaneous Leishmaniasis. However, it was absent in lepromatous leprosy, a state where activated T lymphocytes are not present. We suggest that the local production of IFN-gamma by T cells of the dermal infiltrate induces IP-10 formation in both the dermis and epidermis. IP-10 and Ia then serve as specific markers of immune IFN and its possible influence on effector cells of the cell mediated immune response.

Topics: Animals; Antibody Formation; Chemokine CXCL10; Chemokines, CXC; Cytokines; HLA-DR Antigens; Humans; Hypersensitivity, Delayed; Immunohistochemistry; Interferon-gamma; Keratins; Leishmaniasis; Leprosy; Mice; Skin

Epidermal changes, Ia expression on keratinocytes, Langerhans cell hyperplasia and lymphocyte infiltration were sought in skin lesions of leprosy: 15 borderline tuberculoid (BT), six borderline lepromatous (BL), 17 lepromatous (LL), 13 erythema nodosum leprosum (ENL), six Lucio reactions and nine reversal reactions. All three changes were well developed in BT and reversal reactions. ENL showed well developed keratinocyte Ia and Langerhans cell hyperplasia, but little lymphocytic infiltration. LL and Lucio tissues had some Langerhans cell hyperplasia but little or no keratinocyte Ia or lymphocytic infiltration. BL tissues were so diverse as to suggest two distinct subgroups. These findings are consistent with the hypothesis that keratinocyte Ia expression is an immunohistological sign of a cell-mediated immune (CMI) response. However, the Ia keratinocyte expression found in BL and ENL tissues appears contrary to the undifferentiated macrophages and numerous bacilli found in the lesions. Thus, if a sign of CMI, keratinocyte Ia expression is not a measure of the effectiveness of the response.

Topics: Cell Movement; Epidermis; HLA-D Antigens; HLA-DR Antigens; Humans; Hyperplasia; Keratins; Langerhans Cells; Leprosy; Lymphocytes; Skin

Skin and serum zinc measurements have been made in patients with leprosy with and without trophic skin ulceration and in several other groups. Serum zinc concentrations were decreased in leprosy irrespective of the presence or absence of skin ulceration. Serum zinc concentrations in leprosy were also unrelated to smears positive for Mycobacterium leprae and to the clinical type of leprosy. Since a decrease of the serum zinc was also found in patients with dermatitis herpetiformis and pulmonary tuberculosis it seems likely that the decreased serum zinc in leprosy is a nonspecific metabolic consequence of chronic skin and internal disease. The mean skin zinc concentration in leprosy did not differ significantly from the corresponding value in control subjects, the lack of agreement between serum and skin concentrations being possibly related to the presence of nonexchangeable keratin-bound zinc in skin. Though the clinical significance of lowered serum zinc concentrations in leprosy is uncertain therapeutic trials of zinc treatment in leprosy with trophic skin ulceration seem justifiable.

Topics: Biopsy; Dapsone; Dermatitis Herpetiformis; Humans; Keratins; Leprosy; Mycobacterium leprae; Protein Binding; Serum Albumin; Skin; Skin Ulcer; Tuberculosis, Pulmonary; Zinc