Ninety-one patients with different clinical forms of leprosy, 36 lepromatous (LL), 33 tuberculoid (TL), and 22 dimorphic (DL), and 31 healthy volunteer donors were included in this study. Total complement system (CS) activity was assessed by hemolytic methods, whereas individual components were quantified by the enzyme-linked immunosorbent assay. Under conditions allowing initiation of cascade by the classic pathway (CP) but not alternative pathway (AP) activation, significant CS consumption was detected only in sera from patients with LL. In this group of patients, C4 but not factor B (fB) or C3 was significantly reduced, whereas mannose-binding lectin (MBL) serum levels were significantly higher. These results indicate that the CP is involved in CS activation in patients infected with Mycobacterium leprae manifesting LL clinical form of leprosy. An association is likely between circulating immune complexes and MBL high serum levels for initiation of CS activation in patients with LL form of leprosy.
Leprosy is an infectious disease still highly prevalent in Brazil, having been detected around 27,863 new cases in 2019. Exposure to Mycobacterium leprae may not be sufficient to trigger the disease, which seems to be influenced by host immunogenetics to determine resistance or susceptibility. The purinergic receptor P2X7 plays a crucial role in immunity, inflammation, neurological function, bone homeostasis, and neoplasia and is associated with several infectious and non-infectious diseases. Here, we first compare the P2RX7 expression in RNA-seq experiments from 16 leprosy cases and 16 healthy controls to establish the magnitude of allele-specific expression for single-nucleotide polymorphisms of the gene P2RX7 and to determine the level of gene expression in healthy and diseased skin. In addition, we also evaluated the association of two P2RX7 single-nucleotide polymorphisms (c.1513A>C/rs3751143 and c.1068A>G/rs1718119) with leprosy risk. The expression of P2RX7 was found significantly upregulated at macrophage cells from leprosy patients compared with healthy controls, mainly in macrophages from lepromatous patients. Significant risk for leprosy disease was associated with loss function of rs3751143 homozygous mutant CC [CC vs. AA: p = 0.001; odds ratio (OR) = 1.676, 95% CI = 1.251–2.247] but not with heterozygous AC (AC vs. AA: p = 0.001; OR = 1.429, 95% CI = 1.260–1.621). Contrary, the polymorphic A allele from the gain function of rs1718119 was associated with protection for the development of leprosy, as observed in the dominant model (AA + AG × GG p = 0.0028; OR = 0.03516; CI = 0.1801–0.6864). So, our results suggest that the functional P2X7 purinergic receptor may exert a key role in the Mycobacterium death inside macrophages and inflammatory response, which is necessary to control the disease.
Background: Mycobacterium leprae and Toxoplasma gondii infections are both neglected tropical diseases highly prevalent in Brazil. Infection with certain parasite species can significantly alter susceptibility to other important pathogens, and/or influence the development of pathology. Here we investigated the possible influence of M. leprae/T. gondii co-parasitism on the manifestation of leprosy and its clinical forms. Methods: Participants (n = 291) were recruited in Campos dos Goytacazes city, Rio de Janeiro state, southeast Brazil, from August 2015 to December 2019 and clinically diagnosed for leprosy. Participants were selected based on the presence (patients) or absence (healthy controls) of the leprosy disease. Contacts of patients were also recruited for this study. Serum samples from patients (n = 199) with leprosy, contacts (n = 40) and healthy controls (n = 52) were investigated for levels of IgM and IgG anti-phenolic glycolipid-1 (PGL-1) by ELISA. Additionally, IgG antibody against soluble Toxoplasma antigen (STAg) was measured in sera samples from leprosy patients, contacts and healthy controls for Toxoplasma gondii serology by ELISA. Anti-PGL-1 IgG and IgM levels were compared using one-way ANOVA Kruskal-Wallis or Mann-Whitney, while Spearman test was used to correlate levels of IgG anti-STAg and IgM/ IgG anti-PGL-1 from seropositive and seronegative individuals for T. gondii infection. The risk of T. gondii infection for leprosy disease was assessed using Fisher's test. Results: Levels of IgM anti-PGL-1 antibodies were significantly higher in multibacillary (MB) patients compared to paucibacillary (PB) patients (P = 0.0068). Higher IgM and IgG levels anti-PGL-1 were detected in patients with the lepromatous forms. The serologic prevalence for T. gondii infection was 74.9%. We detected increased anti-STAg antibody levels in leprosy patients (79.4%), reaching 88.8% within those with lepromatous form of this disease. The leprosy risk increase in T. gondii seropositive individuals was twofold (odds ratio [OR] = 2.055; 95% confidence intervals [95% CI]: 1.18-3.51) higher than those seronegative, and considering the lepromatous leprosy risk this increase was even dramatic (OR = 4.33; 95% CI: 1.76-9.69) in T. gondii seropositive individuals. Moreover the leprosy risk in T. gondii seropositive individuals was weakly correlated to the levels of IgG anti-STAg and IgM/IgG anti-PGL-1.
Hypopigmented mycosis fungoides (HMF) is an uncommon variant of cutaneous T-cell lymphoma. It is more frequent in dark-skinned people, particularly children. The HMF diagnose is difficult, especially in early stages because this condition resembles benign skin diseases. Thus is histopathological analysis very important for the diagnosis. We report a case of a 7-year-old child with widespread HMF confirmed by histopathology that showed cells tagging along the dermal/epidermal junction and extending into the epidermis in a pattern of epidermotropism and focal cell aggregates in the epidermis (Pautrier's microabscess). We demonstrate the importance of clinical suspicion for this cutaneous neoplasia in patients with hypopigmentated lesions.
No abstract
The high frequency of MBL2 mutant alleles found in various human populations suggests that they provide some selective advantage. One of the hypotheses is that MBL deficiency may be protective against intracellular pathogens, including Mycobacterium leprae. In this study, we investigated the role of MBL2 in the susceptibility to leprosy. Single-nucleotide variants (SNV) B (rs1800450) and C (rs1800451) in exon 1 of the MBL2 gene and serum MBL concentrations were assessed in 53 patients with leprosy and 68 healthy controls from southeast Brazil by polymerase chain reaction followed by restriction fragment length polymorphism and commercial capture enzyme-linked immunosorbent assay, respectively. The genotyped SNVs were significantly associated with increased protection against leprosy (OR=0.3757, 95% CI=0.1615‒08740, p=0.0273) and more severe forms, including multibacillary (OR=0.3769, 95% CI=0.1447‒0.9818, p=0.0493) and lepromatous (OR=0.2423, 95% CI=0.06547‒0.8968, p=0.0369) leprosy. On the other hand, low-MBL producing genotypes were associated with the protection for leprosy, especially in its more severe forms. Low MBL levels and low MBL producing variants were associated with protection against leprosy and progression to more severe forms of this disease. Moreover, this study highlights MBL as a regulator of immune function in which alterations may affect normal responses to leprosy infection and inflammatory stimuli. Keywords: Leprosy; Mannose binding lectin;
No abstract
Resumo O tema infecções entéricas sexualmente transmissíveis é um dos capítulos que compõem o Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis, publicado pelo Ministério da Saúde do Brasil em 2020. Tal documento foi elaborado com base em evidências científicas e validado em discussões com especialistas. Este artigo apresenta aspectos epidemiológicos e clínicos relacionados a essas infecções, bem como orientações para os gestores quanto ao seu manejo programático e operacional. Objetiva-se auxiliar os profissionais de saúde na triagem, diagnóstico e tratamento das pessoas com infecções entéricas sexualmente transmissíveis e suas parcerias sexuais, além de subsidiar estratégias para ações de vigilância, prevenção e controle desses agravos.
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