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B Naafs

Publications and source records attributed to B Naafs.

At least 19 recordsLinked to original sources
PubMed2006

Two patients coinfected with Mycobacterium leprae and human immunodeficiency virus type 1 and naive for antiretroviral therapy who exhibited type 1 leprosy reactions mimicking the immune reconstitution inflammatory syndrome.

Two case reports of patients with human immunodeficiency virus type 1 (HIV-1) infection who developed leprosy are presented. Both developed type 1 leprosy reactions in the absence of antiretroviral therapy. Reactions have been described for a number of HIV-1- and Mycobacterium leprae-coinfected patients and have been considered to be part of an immune reconstitution inflammatory syndrome (IRIS) since the reactions were usually linked to the administration of highly active antiretroviral therapy. The reports of our two patients suggest that the type 1 reactions in patients with leprosy and HIV may not always be an IRIS manifestation but may be akin to the classical reactional state described for the natural course of leprosy infection, which occurs in leprosy patients due to the fluctuations of the antimycobacterial immune response, whether they are coinfected with HIV or not.

Adult↗
PubMed2004

Immunological crossreactivity of the Mycobacterium leprae CFP-10 with its homologue in Mycobacterium tuberculosis.

Mycobacterium tuberculosis culture filtrate protein-10 (CFP-10) (Rv3874) is considered a promising antigen for the immunodiagnosis of tuberculosis (TB) together with early secreted antigens of M. tuberculosis (ESAT-6). Both ESAT-6 and CFP-10 are encoded by the RD1 region that is deleted from all tested M. bovis bacille Calmette-Guérin (BCG) strains but present in M. leprae, M. tuberculosis, M. bovis, M. kansasii, M. africanum and M. marinum. In this study, the homologue of CFP-10 in M. leprae (ML0050) is identified and characterized. Interferon-gamma production in response to this homologue by T cells from leprosy patients, TB patients and unexposed controls shows that CFP-10 of M. leprae is a potent antigen that crossreacts with CFP-10 of M. tuberculosis at the T-cell level. This crossreactivity has implications for the use of CFP-10 of these mycobacterial species as diagnostic tool in areas endemic for both the diseases.

Amino Acid Sequence↗
PubMed2001

Factors influencing the development of leprosy: an overview.

The clinical manifestations of leprosy vary, seemingly depending on the host's immune response. Mode and route of infection, such as skin versus nasal mucosa, insect bites, sexual and gastroenteral transmission, together with genetic factors that may contribute to the outcome of the infection, including HLA, Lewis factor, Nramp1 and more subtle inherited alterations, are discussed. It is theorized that a balance between host responses elicited by different routes of infection and size and spacing of inocula is responsible for the clinical and immunological manifestations of the disease. Genetic factors and contact with environmental microorganisms may modulate these responses. The final result, resistance, delayed-type hypersensitivity, tolerance, disease or no disease, spectrum and reactions, is most likely reached via the orchestration of the induced cyto- and chemokines.

Humans↗
PubMed1999

HLA-class II-associated control of antigen recognition by T cells in leprosy: a prominent role for the 30/31-kDa antigens.

The recognition of 16 mycobacterial Ags by a panel of T cell lines from leprosy patients and healthy exposed individuals from an endemic population was examined within the context of expressed HLA-DR molecules. Although overall no significant differences were found between the frequencies of Ag recognition in the different subject groups, when Ag-specific T cell responses were examined within the context of HLA-DR, a highly significant difference was found in the recognition of the 30/31-kDa Ag. HLA-DR3 appeared to be associated with high T cell responsiveness to the 30/31-kDa Ag in healthy contacts (p = 0.01), but, conversely, with low T cell responsiveness to this Ag in tuberculoid patients (p = 0.005). Within the group of HLA-DR3-positive individuals, differences in 30/31-kDa directed T cell responsiveness were highly significant not only between healthy individuals and tuberculoid patients (p < 0. 0001), but also between healthy individuals and lepromatous patients (p = 0.009), and consequently between healthy individuals compared with leprosy patients as a group (p < 0.0001). A dominant HLA-DR3-restricted epitope was recognized by healthy contacts in this population. It has been proposed that secreted Ags may dominate acquired immunity early in infection. The low T cell response to the secreted, immunodominant 30/31-kDa Ag in HLA-DR3-positive leprosy patients in this population may result in retarded macrophage activation and delayed bacillary clearance, which in turn may lead to enhanced Ag load followed by T cell-mediated immunopathology.

Antigens, Bacterial↗
PubMed1999

Immunohistological analysis of in situ expression of mycobacterial antigens in skin lesions of leprosy patients across the histopathological spectrum. Association of Mycobacterial lipoarabinomannan (LAM) and Mycobacterium leprae phenolic glycolipid-I (PGL-I) with leprosy reactions.

The presence of mycobacterial antigens in leprosy skin lesions was studied by immunohistological methods using monoclonal antibodies (MAbs) to Mycobacterium leprae-specific phenolic glycolipid I (PGL-I) and to cross-reactive mycobacterial antigens of 36 kd, 65 kd, and lipoarabinomannan (LAM). The staining patterns with MAb to 36 kd and 65 kd were heterogeneous and were also seen in the lesions of other skin diseases. The in situ staining of PGL-I and LAM was seen only in leprosy. Both antigens were abundantly present in infiltrating macrophages in the lesions of untreated multibacillary (MB) patients, whereas only PGL-I was occasionally seen in scattered macrophages in untreated paucibacillary lesions. During treatment, clearance of PGL-I from granulomas in MB lesions occurred before that of LAM, although the former persisted in scattered macrophages in some treated patients. This persistence of PGL-I in the lesions paralleled high serum anti-PGL-I antibody titers but was not indicative for the presence of viable bacilli in the lesions. Interestingly, we also observed a differential expression pattern of PGL-I and LAM in the lesions of MB patients with reactions during the course of the disease as compared with those without reactions. In conclusion, the in situ expression pattern of PGL-I and LAM in MB patients may assist in early diagnosis of reactions versus relapse.

Antibodies, Bacterial↗
PubMed1998

The nose in leprosy: immunohistology of the nasal mucosa.

A detailed study of the nose was undertaken in 40 leprosy patients with different classifications of leprosy and different durations of disease at two hospitals in Brazil. This manuscript describes the immunohistochemical data on cellular infiltrates in the nasal biopsies of those patients. It was surprising that the damage to the whole depth of the nasal mucosa, epithelium and lamina propria was considerable, as was the case in the nasal mucosa which looked relatively normal during clinical inspection. The epithelium showed large holes which looked like very extended goblet cells. Very obvious was the lack of vasoconstriction after cocaine application, and the vessels also showed a lack of staining with factor VIII, possibly indicating a disruption of the endothelium. The number of neurofilaments was extensively reduced in all leprosy groups compared to normal controls. As in the skin, an increased number of CD68+ cells was found in the lamina propria of the nasal mucosa of the lepromatous patients. Contrary to findings in the skin, in the nasal mucosa of the borderline/lepromatous patients the number of CD4+ cells was increased and the number of CD8+ cells was decreased compared to normal controls. The number of CD8+ cells tended to be more reduced when the history of leprosy was longer. It is not clear as yet whether the reduced numbers of CD8+ cells are acquired during infection or whether persons with a low number of CD8+ cells in the nose might have a higher risk of acquiring leprosy.

Adult↗
PubMed1997

IL-2 and IL-12 act in synergy to overcome antigen-specific T cell unresponsiveness in mycobacterial disease.

IL-12 secretion by APC is critical for the development of protective Th1-type responses in mycobacterial (Mycobacterium avium and Mycobacterium tuberculosis) infections in mice. We have studied the role of IL-12 and IL-2 in the generation of Mycobacterium leprae-specific T cell responses in humans. Leprosy patients were defined as low/nonresponders or high responders based on the level of T cell proliferation in M. leprae-stimulated PBMC. In high responders, M. leprae-induced proliferation was markedly suppressed by neutralizing anti-IL-12 mAb (inhibition 55 +/- 6%). Neutralization of IL-2 activity resulted in an inhibition of 77 +/- 4%. Given the importance of endogenous IL-2 and IL-12 in M. leprae-induced responses, we investigated the ability of rIL-2 and rIL-12 to reverse T cell unresponsiveness in low/nonresponder patients. Interestingly, rIL-12 and rIL-2 strongly synergized in restoring both M. leprae-specific T cell proliferation and IFN-gamma secretion almost completely to the level of responder patients. A similar synergy between rIL-2 and rIL-12 was also observed in high responders when suboptimal M. leprae concentrations were used for T cell stimulation. Our data demonstrate a crucial role for endogenous IL-12 and IL-2 in M. leprae-induced T cell activation. Most importantly, we show that rIL-2 and rIL-12 act in synergy to overcome Ag-specific Th1 cell unresponsiveness. These findings may be applicable to the design of antimicrobial and antitumor vaccines.

Animals↗
PubMed1995

Molecular characterization and T-cell-stimulatory capacity of Mycobacterium leprae antigen T5.

A Mycobacterium leprae lambda gt11 clone designated T5 has previously been selected with sera from tuberculoid leprosy patients. Sequence analysis of this clone revealed the presence of two overlapping open reading frames (ORFs) present on the two cDNA strands. The first ORF codes for the serologically recognized antigen, which was fused with the lacZ gene in the lambda gt11 clone. The second ORF, present on the complementary strand, displays strong sequence homology with the aspartyl-tRNA synthetase genes of Escherichia coli and Thermus thermophilus. Here we show that the purified T5-derived product, overexpressed in E. coli, is recognized by T cells of the majority of the leprosy patients tested, including lepromatous leprosy patients who do not respond to whole M. leprae bacilli.

Amino Acid Sequence↗
PubMed1994

[Leprosy in The Netherlands in the period 1970-1991].

OBJECTIVE: To inventory the changes in leprosy epidemiology in the Netherlands. DESIGN: Retrospective. SETTING: Academic Medical Centre (Amsterdam) and University Hospital Dijkzigt (Rotterdam), the Netherlands. METHOD: The medical records of all new leprosy patients in the period 1970-1991 were analysed. RESULTS: Between 1970 and 1991, 622 new leprosy patients were registered; 371 men (59.6%) and 251 women (40.4%). Most patients came from Surinam (73.3%) and Indonesia (7.2%). The mean time lapse between onset and treatment in the Netherlands was 10.1 years. Switching from monotherapy to combination therapy (1979) had no effect on the incidence of reversal reactions (cellular hypersensitivity in immunologically unstable patients), but did affect the incidence of erythema nodosum leprosum during the treatment. CONCLUSION: Leprosy in the Netherlands is an important disease, mainly from Surinam. The main advantage of combination therapy is the shortened duration of treatment. The treatment of choice is the one recommended by the WHO, the combination therapy with rifampicin administration once a month, because of the few adverse effects.

Adult↗
PubMed1994

Morphoea lesions are associated with aberrant expression of membrane cofactor protein and decay accelerating factor in vascular endothelium.

One of the main features of systemic and localized forms of scleroderma is vascular damage, the mechanism of which is not yet understood. Recently, we have shown undetectable or decreased expression of complement regulatory molecules, membrane cofactor protein (MCP) and decay-accelerating factor (DAF), in cutaneous endothelium of patients with systemic sclerosis (SSc). In some patients, CD59 expression in endothelium was also altered. As these molecules protect endothelial cells from damage by autologous complement, their decreased expression could be part of the mechanism of vascular damage in SSc. In the present study, we investigated the expression of MCP, DAF and CD59 in the endothelium of lesional and non-lesional skin of patients with localized morphoea. Normal skin and lesional skin from patients with systemic lupus erythematosus, and three inflammatory diseases, were included as relevant controls. The results showed that the extent of expression of the three molecules in non-lesional skin of patients with morphoea, on all the skin cells and structures, was identical to that of normal skin. In lesional skin, however, the expression of MCP and DAF in endothelium was either undetectable or only present to a very slight degree. CD59 expression in endothelium in lesional skin was normal. No such aberrant expression was observed in the lesions of any of the control diseases. These results indicate a decreased ability of endothelial cells in lesional areas to protect themselves from autologous complement, and this could contribute to vascular damage in morphoea lesions.

Antigens, CD↗
PubMed1994

Mycetoma.

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Combined Modality Therapy↗