Biomedical subjects

M Amicosante

Publications and source records attributed to M Amicosante.

24 records · Page 2Linked to original sources

PubMed1993

Early abnormalities of the antibody response against Mycobacterium tuberculosis in human immunodeficiency virus infection.

Among human immunodeficiency virus (HIV)-infected persons, those who react against purified protein derivative (PPD) have higher risk of tuberculosis. Since PPD testing has limited predictive power in HIV-positive populations, new markers of antituberculous immunity were sought by analyzing antibodies to Mycobacterium tuberculosis antigens (PPD and its fraction A60) in 102 HIV-positive subjects, some PPD-positive and some PPD-negative, and in 23 HIV-positive tuberculosis patients. ELISA and Western blotting were used. Forty HIV-negative healthy subjects and 40 HIV-negative tuberculosis patients were evaluated as controls. While all those HIV-negative and PPD-positive had IgG antibodies recognizing the 38-, 28-, and 19-kDa M. tuberculosis antigens, only 26% of those HIV-positive and PPD-positive (all with < 400 CD4+ cells/mm3) and none of the HIV-positive tuberculosis patients recognized them, indicating that the lack of IgG against those antigens, in the presence of a specific IgM response, is a marker of immunodeficiency.

Adolescent↗

PubMed1993

Antibody repertoire against the A60 antigen complex during the course of pulmonary tuberculosis.

The A60 antigen complex is a Mycobacterium bovis (BCG) highly immunodominant antigen containing both B and T-cell epitopes. Clinical-serological studies show that elevated anti-A60 titres are present during tuberculosis. We wished to analyze in detail antibody responses against A60 components during the course of tuberculosis. A mixed longitudinal study was designed including individuals at the onset of tuberculosis, during treatment and after resolution of the disease. The anti-A60 repertoire was analyzed using a western blot assay with A60 as the antigen. While PPD- normals recognized only the 65 kDa heat shock protein (HSP), PPD+ normal individuals displayed low levels of anti-A60 antibodies against dominant antigens. There were immunoglobulin M (IgM) and immunoglobulin G (IgG) consistent with response to a latent infection. Onset tuberculosis was characterized by IgM and IgG antibodies against 52 to 28 kDa antigens; IgM response being limited to earlier phases of the disease. In contrast, IgM antibodies against 25 to 14 kDa antigens appeared only 2-6 months after disease onset. The antibody repertoire of chemotherapy-treated, resolved tuberculosis was exclusively IgG in isotype, as for a memory-type response. Thus, western blot analysis with A60 identifies typical antibody patterns associated with different clinical phases of tuberculosis infection. Such approach may help in identifying new single antigens for serologic diagnosis of active tuberculosis.

Adult↗

PubMed1992

[Mycobacterium tuberculosis. From the gene to the diagnosis].

Pulmonary tuberculosis still in on the list of the world major health problems. Tuberculosis has not been eradicated yet, from developing countries. Furthermore, its incidence is increasing in the industrialized world, due to the human immunodeficiency virus (HIV) epidemic. In this regard, atypical clinical presentation of tuberculosis in individuals who have a deficient immune system, such as those at risk of tuberculosis because of HIV infection, makes the diagnostic process more difficult. Tuberculosis cases are often diagnosed later in HIV individuals compared to non-HIV individuals. The ensuing greater risk of contagion thus requires rapid and sensitive diagnostic protocols. In this context, several biotechnological tools have been developed that can be applied to the diagnosis of tuberculosis. M. tuberculosis genes have been cloned, monoclonal antibodies against pure proteins have been produced, thus enabling researchers to generate molecular and biochemical probes. As a consequence, DNA hybridization and DNA amplification techniques have been applied to the detection of mycobacteria, and ELISA kits of high sensitivity are been already made available. In regard to the latter, it is likely that monospecific and highly sensitive immunoassays will be developed that are directed against "active disease" immunodominant antigens. It may thus be expected that future new technologies will supplement the traditional tools for the diagnosis of tuberculosis and rapid diagnosis protocols will be available to chest clinicians in a foreseeable future.

Antibodies, Bacterial↗

PubMedDate not supplied

Different cytokine production and effector/memory dynamics of alpha beta+ or gamma delta+ T-cell subsets in the peripheral blood of patients with active pulmonary tuberculosis.

Immunity to M.tuberculosis (MTB) infection consists of interactions between various T-cell subsets that control the infection and prevent further reactivation. We analysed the effector/memory T-cell dynamics and cytokines production in the peripheral blood of patients with pulmonary tuberculosis (TB). We observed that the frequency of CD4+ T-cell effectors was significantly increased during active TB, confirming a major role of this T-cell subset in TB immunity. Pre-terminally differentiated CD8+ T-lymphocytes were increased in the peripheral blood as well. In contrast, we observed a reduced number of effector mycobacteria-reactive gammadelta+ T-lymphocytes with a specific defects in reacting to mycobacterial nonpeptidic antigens, suggesting that this innate response is rapidly lost during TB infection. Nevertheless, the frequency of gammadelta+ T-cells effectors in TB patients was higher than the alphabeta+ T-cell response to peptide from MTB-ESAT-6 protein and quantitatively similar to PPD reactivity. Thus, alphabeta+ and gammadelta+ T-cell differentiation and function are differently triggered by active TB infection.

Adult↗

PubMedDate not supplied

Role of the HLA-DP Glu 69 and the TNF-alpha TNF-alpha 2 gene markers in susceptibility to beryllium hypersensitivity.

Berylliosis is an environmental chronic inflammatory disorder of the lung caused by inhalation of beryllium dusts, characterized by the accumulation of CD4+ T cells and macrophages in the lower respiratory tract. Beryllium presentation to CD4+ T cells from patients with berylliosis results in T cell activation and these Be-specific CD4+ T cells undergo clonal proliferation and Th1-type cytokine production such as interleukin-2, interferon-gamma and tumor necrosis factor-alpha. In exposed workers, genetic susceptibility to this granulomatous disorder is associated with major histocompatibility gene and the TNF-alpha gene. The HLA-DP glutamic 69 residue was shown to be the MHC genetic marker associated with disease susceptibility; furthermore the TNF-alpha TNFA-308*2 allele was found to be independently associated with HLA-DP Glu69 in the determination of berylliosis risk.

Alleles↗

PubMedDate not supplied

[Berylliosis in Italy: a case of "sarcoidosis" under the threshold limit value].

BACKGROUND: Berylliosis is caused by a chronic immune reaction to beryllium; in Italy the first case of beryllium exposure-related disease was described in 1935 by Fabroni-Marradi and two additional cases of beryllium disease were subsequently described by Ambrosi and co-workers in 1968. No case has since been recognized using the standardized criteria including immunological testing. OBJECTIVES: To describe a case report of clinically significant berylliosis that occurred in a man exposed to beryllium for ten years in the workplace at concentrations below the permitted threshold limit value. METHODS: The man complained of dyspnoea, dry cough, weakness and weight loss for the past year and was at first diagnosed as suffering from sarcoidosis because of increased angiotensin converting enzyme levels, alteration of hepatic and renal functional indexes, the presence of diffused reticulo-nodular lung abnormalities with high resolution computed tomography that also showed enlarged mediastinal lymph nodes, abnormal lung physiology with reduced diffusion capacity and a bronchial biopsy showing granulomatous lesions. Because of the occupational history immunological testing and high resolution HLA class II typing were performed. RESULTS: The high response to beryllium in the lymphocytes proliferation test and the HLA typing which revealed the presence of the two susceptibility markers HLA-DPGlu69 and HLA-DRPhe47 led to a diagnosis of berylliosis. CONCLUSIONS: The importance is stressed of suspecting a diagnosis of berylliosis in the proper occupational contexts and encouraging the use of immunological tests for diagnosis, and also the need for critical revision of the permitted threshold limit values.

Adult↗