American cutaneous leishmaniasis, lepromatous leprosy, and pulmonary tuberculosis coinfection with downregulation of the T-helper 1 cell response.

Cutaneous leishmaniasis, leprosy, and tuberculosis are caused by intracellular pathogens whose development depends on impaired cell-mediated immunity. We report an exceptional triple association of American cutaneous leishmaniasis, lepromatous leprosy, and pulmonary tuberculosis in a man with no recognized immunodeficiency. Normal immunological assessment of the interferon-gamma pathway does not support the hypothesis of a genetic defect in any of the genes involved in the T helper (Th)-1 cytokine cascade in this patient. Unresponsiveness to interleukin (IL)-12 of his T cells after stimulation with Leishmania guyanensis, Mycobacterium bovis bacille Calmette-Guérin, and Mycobacterium leprae antigens suggested the inability to mount an appropriate Th cell response to upregulate the IL-12 receptor expression.

Antibodies to diverse lipids in the serum of patients with clinically cured leprosy and tuberculosis.

In this study we looked for the presence of antibodies to cardiolipin, cerebrosides, and whole lipids extracted from M. leprae, M. tuberculosis and M. habana, in the serum of patients with clinically cured lepromatous leprosy (sixteen) or tuberculosis (sixteen), 8 to 12 months after arresting the corresponding multi-drug therapy (MDT). Compared to healthy controls (sixteen), both leprosy and tuberculosis ex-patients had still significant levels of antibodies to the three mycobacterial lipids but no detectable levels of antibodies to cardiolipin or cerebroside lipids. Although leprosy and tuberculosis sera recognized the homologous mycobacterial lipids in a preferential fashion, all of them, on the average, reacted more strongly with the lipids of M. habana. This observation backs up, in a certain way, the proposition of using M. habana as a prospective vaccine for leprosy and tuberculosis.

Molecular and immunological characterization of the highly conserved antigen 84 from Mycobacterium tuberculosis and Mycobacterium leprae.

Crossed immunoelectrophoresis (CIE) has been used to develop a reference system for classifying mycobacterial antigens. The subsequent use of specific antibodies allowed further determination of antigens by molecular weight. The monoclonal antibody F126-2, originally raised against a 34-kDa antigen of Mycobacterium kansasii, reacted with antigen 84 (Ag84) in the CIE reference system for Mycobacterium bovis BCG and Mycobacterium tuberculosis. To characterize Ag84, we screened a lambda gt11 gene library from M. tuberculosis with antibody F126-2 and identified the encoding gene. The corresponding Mycobacterium leprae Ag84 gene was subsequently selected from a cosmid library, using the M. tuberculosis gene as a probe. Both genes were expressed as 34-kDa proteins in Escherichia coli, and the recombinant proteins indeed corresponded to Ag84 in the CIE reference system. The derived amino acid sequences of the M. tuberculosis and M. leprae proteins showed 85% identity, which indicates that Ag84 constitutes a group of highly conserved mycobacterial antigens. Antibodies of almost 60% of lepromatous leprosy patients responded to Ag84, indicating that the protein is highly immunogenic following infection in multibacillary leprosy.

Serum angiotensin converting enzyme in respiratory diseases.

More than 1700 estimations of serum angiotensin converting enzyme (SACE) were undertaken, mostly in respiratory disorders, to assess its value as a specific and/or a sensitive indicator of different diseases. Though highest levels were found in lepromatous leprosy consistently, it was also found almost always elevated in active stages of sarcoidosis. Since it is raised in a variety of respiratory disorders, it is not a specific diagnostic test. It is, however, a fairly sensitive index of disease activity in sarcoidosis whether on treatment or not. Sudden elevation, after a prolonged period of low or normal values may indicate relapse in sarcoidosis.

[Angiotensin converting enzyme in the blood serum of patients with tuberculosis and leprosy]. / Angiotenzinprevrashchaiushchii ferment v syvorotke krovi bol'nykh tuberkulezom i leproi.

Angiotensin-converting enzyme (ACE) levels in the serum of 15 patients with pulmonary tuberculosis and 9 with leprosy were measured by means of a spectrophotometric method. The serum produced from 10 blood donors was used as a control. Leprosy is accompanied by a sharp drop of ACE levels, which is attributed by the authors to a cellular immunodeficiency. In case of tuberculosis, a higher ACE level in blood often follows fibrosis formed in the lung along with a tuberculin hyperergia. The opinion that the ACE level reflects the tuberculosis or leprosy activity as well as the granulomatous tissue extension in tuberculosis patients has not been confirmed.

Total and anti-mycobacterial IgE levels in serum from patients with tuberculosis and leprosy.

A radioallergosorbent assay (RAST) was developed and used to determine the levels of IgE antibodies to soluble antigens of Mycobacterium tuberculosis (BCG vaccine strain) in sera from patients with tuberculosis and leprosy and in healthy control subjects. Total IgE levels in the same sera were quantitated with a commercial radioimmunoassay kit. Patients with tuberculosis and leprosy had higher total and specific IgE levels than the control groups but the overlap of levels in patients and controls was too great to render the difference diagnostically useful. Specific IgE levels were elevated in both tuberculosis and leprosy patients, suggesting that this antibody response is towards the shared mycobacterial antigens. No differences in total or specific IgE levels were found between healthy hospital workers occupationally exposed to patients with tuberculosis and factory workers who are not exposed.

Immunological and clinical features of smear-positive pulmonary tuberculosis in East Java.

The immunological and clinical features of 90 Javanese patients with smear -positive pulmonary tuberculosis were investigated. Many of the patients had advanced disease at the time of diagnosis and haemoptysis was common, especially in patients with cavitating lesions. Most patients had a significant elevation of one or more non-specific indicators of inflammation (erythrocyte sedimentation rate, third complement component, factor B and C-reactive protein). Rheumatoid factor was detected in 21% of the patients and was significantly associated with high levels of antibodies to M. tuberculosis in the IgM class. Five distinct responses were elicited by tuberculin testing; the most marked occurred at 24 hours. The degree of reaction at 6-8 hours correlated significantly with the levels of specific antibodies in the IgG and IgA classes and the 48 hour response correlated, although less markedly, with specific antibodies in the IgG class. Neither the degree of skin test reactivity nor the level of specific antimycobacterial antibodies correlated with the extent of disease as assessed radiologically. Nine per cent of the patients were skin-test negative at 48 hours but did not differ clinically, as a group, from tuberculin positive patients. It was not possible to place the cases in a spectrum of immunological responses similar to that occurring in leprosy and it is postulated that this is due to differences in the relevance to protection of the various immunological mechanisms in the two diseases. The need to establish more rigorous criteria for assessing the immune responses in tuberculosis and for studying the interactions between the protective and non-protective reactions is stressed.

Trophic skin ulceration of leprosy: skin and serum zinc concentrations.

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.