Salivary anti-PGL-1 IgM may indicate active transmission of Mycobacterium leprae among young people under 16 years of age

Abstract Considering that the main route of Mycobacterium leprae transmission is the upper respiratory tract, detection of salivary antibodies can be a useful tool for diagnosing early infection. The study aimed to analyze salivary anti-PGL-1 IgA and IgM antibodies in 169 children aged 4-16 years old, who lived nearby or inside the house of multibacillary or paucibacillary leprosy patients in two endemic cities in Alagoas State - Brazil. Salivary anti-PGL-1 antibodies were quantified by modified ELISA method. The frequency of contact and clinical form of the index case were significantly associated with salivary antibody levels. High frequency of IgM positivity strongly suggests active transmission of M. leprae in these communities. We suggest in the present work that salivary anti-PGL IgA and IgM are important biomarkers to be used for identifying communities with probable active transmission of M. leprae.

Estudo da mucosa nasal de contatos de hanseníase, com positividade para o antígeno glicolipídio fenólico 1 / Nasal mucosa study of leprosy contacts with positive serology for the phenolic glycolipid 1 antigen

A hanseníase é uma doença infecciosa de evolução crônica causada pelo Mycobacterium leprae que acomete com maior frequência a mucosa nasal. Esse acometimento independe da forma clínica da doença e pode ocorrer mesmo antes do aparecimento de lesões na pele ou em outras partes do corpo. Faz-se necessário a vigilância epidemiológica dos contatos de casos novos de hanseníase para o diagnóstico precoce da doença. OBJETIVOS: Identificar lesões específicas e precoces de hanseníase por meio de exame endoscópico, baciloscópico, histopatológico e da reação em cadeia da polimerase em Tempo Real da mucosa das cavidades nasais dos contatos domiciliares e peridomiciliares com sorologia positiva para o antígeno glicolipídio fenólico. MATERIAL E MÉTODOS: Estudo prospectivo transversal em 31 contatos de pacientes de hanseníase com sorologia positiva (PGL-1), 05 controles negativos e 01 positivo no período de 2003 a 2006. RESULTADOS: Entre os contatos soropositivos a PCR-RT foi positiva para a presença de DNA de M. leprae em 06 (19,35 por cento) destes e o maior número de cópias do genoma do bacilo foi encontrado no contato que adoeceu. CONCLUSÃO: Isoladamente os exames da mucosa nasal não permitiram o diagnóstico precoce da hanseníase, mas com a combinação de vários métodos, o exame dos contatos pôde ajudar na identificação da infecção subclínica e monitoramento daqueles que poderiam ter papel importante na transmissão da doença.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The disease more frequently affects the nasal mucosa and can occur independently of its clinical form or even before lesions on the skin or on other parts of the body. It is necessary to employ epidemiological surveillance of household contacts with new leprosy cases for early disease diagnosis. AIM: identify specific and early leprosy lesions through endoscopic, baciloscopy, histopathology exams, and real time polymerase chain reaction of the nasal cavity mucosa on household and peridomiciliary contacts with positive serology for the phenolic glycolipid 1 antigen. METHODOLOGY: Between 2003 at 2006 there was a prospective cross-sectional clinical study with 31 contacts with patients with leprosy with positive serology against PGL-1, 05 negative controls and 01 positive control. RESULTS: Between seropositive contacts, real-time PCR was positive for M. leprae DNA in 06 (19.35 percent) of them and the higher number of genome copies were found in contacts who became sick. CONCLUSION: Nasal mucosa tests alone did not enable the early diagnosis of Leprosy. However, through the combination of various methods, tests on the contacts can help identify subclinical infection and monitor the contacts that could be responsible for spreading the disease.

An immunohistochemical, clinical and electroneuromyographic correlative study of the neural markers in the neuritic form of leprosy

The nerve biopsies of 11 patients with pure neuritic leprosy were submitted to routine diagnostic procedures and immunoperoxidase staining with antibodies against axonal (neurofilament, nerve growth factor receptor (NGFr), and protein gene product (PGP) 9.5) and Schwann cell (myelin basic protein, S-100 protein, and NGFr) markers. Two pairs of non-adjacent histological cross-sections of the peripheral nerve were removed for quantification. All the fascicles of the nerve were examined with a 10X-ocular and 40X-objective lens. The immunohistochemistry results were compared to the results of semithin section analysis and clinical and electroneuromyographic data. Neurofilament staining was reduced in 100 percent of the neuritic biopsies. NGFr positivity was also reduced in 81.8 percent, PGP staining in 100 percent of the affected nerves, S100 positivity in 90.9 percent, and myelin basic protein immunoreactivity in 90.9 percent. Hypoesthesia was associated with decreased NGFr (81.8 percent) and PGP staining (90.9 percent). Reduced potential amplitudes (electroneuromyographic data) were found to be associated with reduced PGP 9.5 (63.6 percent) and nerve fiber neurofilament staining (45.4 percent) by immunohistochemistry and with loss of myelinated fibers (100 percent) by semithin section analysis. On the other hand, the small fibers (immunoreactive dots) seen amid inflammatory cells continued to be present even after 40 percent of the larger myelinated fibers had disappeared. The present study shows an in-depth view of the destructive effects of leprosy upon the expression of neural markers and the integrity of nerve fiber. The association of these structural changes with the clinical and electroneuromyographic manifestations of leprosy peripheral neuropathy was also discussed.

Postnatal changes in the brain lipids, glycolipids and gangliosides of rats exposed to arrack/ethanol during gestation and lactation.

Effects of exposure of an alcoholic beverage (arrack and its equivalent quantity of alcohol throughout pregnancy and lactation on brain lipids were investigated. Female rats were exposed to arrack (12.00 ml/kg body weigh/day) and ethanol (4.00 g/kg body weight day) before conception and throughout gestation and lactation. For 21 days pups were nursed by their own mothers, afterwards they were fed normal laboratory feed. We found that the level of cholesterol, phospholipids, triacylglycerols, free fatty acids, cerebrosides, ceramide dihexosides, ceramide polyhexosides, sulfatids,, mono and diglycosyl diglycerides and gangliosides were increased in the brain of 21st and 45th day pups. The alterations in the glycolipid profile of the brain persisted even when pups were not directly exposed to alcohol. These alterations in the glycolipid and ganglioside metabolism may be associated with the developmental abnormalities of the brain seen in FAS. The elevation produced in the glycolipid profile of arrack administered pups were more than that caused by its equivalent quantity of ethanol. This suggested an interaction of congeners in the arrack with the alcohol.

Valor pronóstico de los anticuerpos anti-glicolípidos de músculo esquelético en la angina inestable / Prognostic value of anti-skeletal muscle glycolipid antibodies in unstable angina

Se estudió si la determinación del nivel de anticuerpos anti-glicolípidos de músculo esquelético, un marcador de rechazo agudo en el trasplante cardíaco, podía representar un predictor de pronóstico adverso durante la hospitalización de pacientes con angina inestable como ocurre con el aumento de las troponinas cardíacas T e I. Se investigó la presencia y título de anticuerpos anti-glicolípidos de músculo esuqlético, por el método ELISA en el suero de 50 pacientes con angina inestable, al momento de la admisión y 24 h después. El descenso en el título de anticuerpos a las 24 h fue un predictor de la ocurrencia de eventos cardíacos adversos (muerte, infarto agudo de miocardio, revascularización de urgencia y angina refractaria) durante la hospitalización, especialmente en pacientes con antecedentes de infarto de miocardio previo, y es aparentemente para este grupo un mejor predictor de evolución que la determinación de las troponinas cardíacas T e I

Is PGL-1 also present in Leishmania donovani promastigotes?

A soluble antigen complex (SAC) derived from the ruptured promastigotes of Leishmania donovani parasites (LD-SAC) was used for complement fixation test (CFT) in leprosy Cases of tuberculoid and borderline tuberculoid leprosy, post-kala azar dermal leishmaniasis (TT, BT, PKDL) and control sera gave negative CFT. Smear-positive cases of borderline (BB, BL) and lepromatous (LL) leprosy and drug-resisting cases of pulmonary tuberculosis gave positive CFT; smear-negative cases of LL leprosy sera also gave positive CFT. Sera of smear-negative inactive LL patients contained only PGL-1 and PDIM antigens for a long time after they become inactive. Therefore, the positive CFT in inactive LL makes us suspect whether PGL-1 is present in LD promastigotes.

Metabolism of GPIs in mammalian cells

In Trypanosoma brucei, glycosylphosphatidylinositol (GPI) anchors of proteins and free GPIs with identical structures have been characterized. This identity provides strong presumptive evidence that the free GPIs are in fact precursors of the GPI anchors on proteins. In mammalian tissues, however, rather consistent differences in the structures of free GPIs and GPI anchors are observed. The terminal GPIs produced by the mammalian biosynthetic pathway differ from GPI anchors in being almost exclusively fatty acid acylated on the inositol residue, having a greater number of phosphoethanolamine residues, and perhaps in containing a greater percentage of diacylglycerol components. While in principle these differences could be reconciled by remodeling reactions before or after attachment of GPI anchors, it is possible that some of the mammalian free GPIs play cellular roles other than as anchor precursors. We have approached this question by studying the lifetimes of the last three GPIs on the biosynthetic pathway, denoted H6, H7 and H8, in K562 cells and in K562 mutant designated class K that is devoid of GPI-anchored proteins. Pulse-chase metabolic labeling with [3H]-mannose indicated that H6 was a precursor of H7 and H8 and that the H8 lifetime was more than one hour in the parental cells and even longer in the mutant. Preliminary data indicated that the majority of each of the three GPIs was localized in the plasma membrane fraction rather than the endoplasmic reticulum. These observations argue that mammalian GPIs are not utilized exclusively as GPI anchor precursors

A preliminary examination of the major integral membrane protein antigens of Schistosoma japonicum and Schistosoma mansoni adult worms for glycosyl-phosphatidylinositol membrane anchors.

Integral membrane protein (IMP) antigens isolated from S. japonicum and S. mansoni adult worms using Triton X-114 phase partitioning were treated with phosphatidylinositol-specific phospholipase C (piPLC). Following piPLC treatment, only one IMP antigen of 58 kDa from each species was released from the hydrophobic fraction and remained soluble in the absence of detergent. An additional 23 kDa antigen was identified following piPLC treatment of S. japonicum IMP's. This molecule has been previously characterized as an important species specific immunodiagnostic antigen. Alkaline phosphatase activity was observed in both the detergent and aqueous phases following treatment with piPLC but only in the hydrophobic fraction of the controls. These data suggest that only a small number of IMP antigens from both S. japonicum and S. mansoni adult worms possess glycosyl-phosphatidylinositol (GPI) lipid membrane anchors in a form which can be hydrolysed by a heterologous piPLC.