Significance of antibodies to phenolic glycolipid-I in leprosy diagnosis.

A gelatin particle agglutination assay for the detection of anti PGL-I antibodies in 40 clinically diagnosed and variously classified groups of leprosy cases revealed elevated PGL-I antibody titers in 85% of cases. In contrast, the slit-skin smear examination was positive in only 30% of cases. It was further observed that, out of 28 cases with Bacteriological Index (B.I.) zero, 22 cases (78.5%) had significant levels of PGL-I antibodies. There was no case in which the slit skin smear was positive and the PGL-I antibody titer was not significant. The elevated titers of PGL-I antibody better correlated (84%) with histopathological findings than did B.I. Thus it was concluded that estimation of PGL-I antibody titer is a better supplement to clinical diagnosis than B.I. Significant levels of PGL-I antibody were seen in 85% of cases who had no earlier chemotherapy or were treated for less than 2 months. Similar findings were observed in 12 patients who were on MDT for more than 5 months but for less than 2 years. In order to determine the significance of anti PGL-I antibodies in monitoring the response of patients to chemotherapy, a longer follow up with a greater number of cases should be contemplated.     

Secondary Syphilis Mimicking Borderline (BL) Leprosy

A young woman with syphilids resembling borderline lepromatous (BL) leprosy is being described. This is yet another addition to its already well-documented manifestations. The high prevalence of leprosy and syphilis augments the epidemiological significance of the case.     

Early infection with M. leprae and antibodies to phenolic glycolipid-I in the nine-banded armadillo

Nine-banded armadillos were intravenously infected with 10(9) M. leprae. IgM antibodies to PGL-I were evaluated three times during the six months before and every two months after the infection. A thorough autopsy examination was done on animals that died or were sacrificed at intervals of 3, 4, 6, 12, 15 and 18 months after the infection. Three animals which had acquired the infection in the wild and one experimentally infected animal showed significant increases in antibody levels corresponding to their high bacterial load. In the other five experimentally infected animals, M. leprae infection was established in the cells of the reticulo endothelial system (RES) long before the IgM antibody levels to PGL-I became positive. It is possible that in human leprosy also M. leprae may enter and multiply in the RES initiating antibody production during the incubation period before clinical disease with neuritis becomes manifest.     

麻风患者治疗前后血清麻风杆菌特异性抗原和抗体的变化

用免疫斑点试验改良法（Ｍ－Ｄｏｔ－ＥＬＩＳＡ）和酶联免疫吸附试验（ＥＬＩＳＡ）对１０例多菌型麻风患者治疗前后的９９份血清进行了ＰＧＬ－Ｉ抗原和抗体检测。结果表明治疗前后及治疗中各段时间的抗原下降速度远快于抗体，二者之间有非常显著性差异（Ｕ＝９．０５，＞２．５８，Ｐ＜０，０１）。抗原量的下降以治疗后第１个月最快（７９．１４％），治疗第３个月时已下降９９％以上，这提示抗原的检测可用于监测多菌型麻风的早期疗效，在发现耐药和抗麻风新药筛选方面亦有应用价值。     

Serological detection of leprosy employing Mycobacterium leprae derived serine-rich 45 kDa, ESAT-6, CFP-10 and PGL-I: a compilation of data from studies in Indian populations

This article is a compilation of our findings recorded in the recent past where we have investigated the serological performance of Mycobacterium leprae antigens like-serine-rich 45 kDa protein (45 kD), early secretary antigenic target-6 (ESAT-6), culture filtrate protein-10 (CFP-10) and phenolic glycolipid-I (PGL-I) for detection (employing antibody detecting ELISA) of leprosy patients, particularly those belonging to the paucibacillary (PB) group. All of these antigens were capable of detecting, by themselves the majority (82-100%) of multibacillary (MB) patients. However, with respect to PB patients, only 18-47% (i.e. less than half) of the cases could be detected. Based on the results of serological assays for each of the four antigens separately a combinatorial approach was performed for these antigens, which increased the sensitivity for detection of PB patients to 73%, giving 36% improvement over conventional PGL-I based ELISA. Thus, the multi-antigenic serological approach is worthwhile for its establishment for detection of leprosy patients. Since ESAT-6 and CFP-10 are secreted proteins by nature, antibodies against them are worth exploring for detection of early infections and for monitoring of treatment efficiency. Nevertheless, efforts towards identification of more new antigens with serological potential are still desirable in order to further improve the detection rate of leprosy.     

A dot enzyme immunoassay for detection of IgM antibodies against phenolic glycolipid-I in sera from leprosy patients

A visual dipstick dot enzyme immunoassay (EIA) for diagnosis of leprosy is described. The assay is based on detection of IgM antibodies against phenolic glycolipid (PGL-I) in sera from leprosy patients. The antigen (PGL-I or synthetic disaccharide of PGL-I) was dotted on a nitrocellulose pad stuck on a plastic strip (dipstick). Sera were used at a dilution of 1:200. Peroxidase coupled mouse anti-human IgM monoclonal antibodies were used as the conjugate. A positive test gave a blue dot against a white background. The test was highly specific for leprosy, and was quite sensitive for detection of bacilliferous (BL/LL) leprosy. The antigen dotted and preblocked dipsticks stored at room temperature upto 4 months of observation period, were unable in the assay.     

Leprosy in a University Hospital in Southern Brazil

BACKGROUND

Leprosy is an infectious disease that may lead to irreversible nerve damage, compromising patient''s quality of life and leading to loss of working years.

OBJECTIVES

To evaluate the epidemiological profile of patients followed at a University Hospital.

MATERIALS AND METHODS

This is a retrospective observational study, based on a review of medical records. We studied the clinical and epidemiological features of patients with leprosy monitored at the Hospital de Clínicas of the Federal University of Paraná between January 2005 and January 2010.

RESULTS

The mean age was 47.51, while 35.94% of patients were aged 41-60. The male:female rate was 1.8:1. The most prevalent occupations were: retired, students or rural workers. Patients came mainly from Curitiba or nearby areas, but there were also patients from the countryside. The mean diagnostic delay was 24.57 months. Multibacillary forms prevailed, with the lepromatous variety being the most common, closely followed by the borderline type. Neural enlargement was found in more than 50% of the patients and 48.44% of them developed reactional states. Hemolysis was the most commonly detected drug side effect. Initial functional evaluation was possible in 70% of patients, 55% of whom had disabilities upon diagnosis. The most prevalent associated disease was hypertension.

CONCLUSIONS

This study showed an important diagnostic delay and a high rate of sequelae in this specific population. Brazil is one of the few remaining countries that has not yet eradicated leprosy and it is important to improve health policies in order to prevent sequelae and achieve eradication.     

The role of Mycobacterium leprae phenolic glycolipid I (PGL-I) in serodiagnosis and in the pathogenesis of leprosy

PGL-I (phenolic glycolipid I) emerged in the early 1980s on the one hand as part of intensive efforts to define the typing antigens of a host of Mycobacterium spp. and also from characterisation of the lipids of skin biopsies from highly bacillary positive lepromatous leprosy patients. PGL-I, despite its extreme lipophilicity due to its inherent phthiocerol dimycocerosyl component, is highly antigenic evoking high titre IgM antibodies in lepromatous leprosy patients, attributable largely to the unique 3,6-di-O-methyl-beta-D-glucosyl entity at the non-reducing terminus of its trisaccharide. PGL-I itself or in the form of semisynthetic neoglycoproteins containing the synthetic terminal disaccharide or the whole trisaccharide chemically conjugated to such as bovine or human serum albumin, has found its greatest utility in the serological diagnosis, confirmation and management of lepromatous leprosy. PGL-I has also been implicated in the tropism of M. leprae for Schwann cells, through specific binding to laminin, and to play an important role in downregulation of the inflammatory immune response and inhibition of dendritic cell maturation and activation, thereby facilitating the persistence of M. leprae/leprosy.     

Comparative evaluation of enzyme immunoassays based on synthetic glycoconjugates and phenolic glycolipid-I for immunodiagnosis of leprosy

Enzyme immunoassays (EIAs) based on synthetic glycoconjugates containing the terminal monosaccharide (M-BGG) or disaccharide (ND-BSA) residue of the trisaccharide component of phenolic glycolipid-I (PGL-I), for immunodiagnosis of leprosy are described. The results of the assays were compared with that of the EIA using PGL-I. All the three assays were highly specific for leprosy. The per cent positivity of active lepromatous leprosy (LL) patients with M-BGG was 78.05 in comparison to 85.36 with ND-BSA and 82.11 with PGL-I. Similarly, the positivity of tuberculoid (TT) leprosy patients in M-BGG assay was lower than that in EIAs using ND-BSA or PGL-I. However, the difference in the positivity of individual category of leprosy patients in the three EIAs was not statistically significant. The correlation between absorbance values of leprosy sera in EIAs based on M-BGG and PGL-I, as well as that in assays using ND-BSA and PGL-I was statistically significant.     

上转换发光技术侧流免疫夹心法检测59例麻风患者和87例家庭接触者PGL-I抗体结果分析

目的：评估上转换发光技术侧流免疫夹心法（UCP-LFA）检测PGL-I抗体对麻风接触者发病风险预测的价值。方法：采用UCP-LFA 方法检测贵州59例麻风患者、87例家庭接触者和55例健康对照进行PGL-I抗体水平。数据统计采用SPSS 20.0进行卡方分析。根据ROC曲线确定临界值。结果：麻风患者中PGL-I抗体阳性率为81.4%、麻风接触者为5.7%、健康对照人群为1.8%,三组人群PGL-I抗体阳性率差异有统计学意义（χ2 =126.47,P<0.005）。少菌型和多菌型PGL-I抗体阳性率分别为40% 和89%,差异有统计学意义（χ2=13.386,P<0.005）。BI+、BI-患者PGL-I抗体阳性率分别为83%和0%,差异有统计学意义（χ2 =17.560,P<0.005）。结论：麻风患者PGL-1抗体阳性率>麻风病接触者>正常对照,多菌型PGL-1抗体阳性率高于少菌型,提示PGL-I IgM抗体水平对麻风发病有一定的预测作用。     

Quality of life in patients with lepromatous leprosy in China

Background Leprosy has an impact on patients’ quality of life (QoL). However, there has been no study specifically on the impact of the severest type of leprosy‐lepromatous leprosy on QoL. Objective To describe the use of Dermatology Life Quality Index (DLQI) among patients with lepromatous leprosy in China. Methods Sixty‐four inpatients with lepromatous leprosy of Shangluo hospital and Hanzhong hospital and sixty‐four controls (healthy volunteers or patients with other dermatoses) matched for age and gender were asked to complete DLQI questionnaires from 2 September 2008 to 20 December 2008. Extensive data were collected besides DLQI, including demographic data and disease‐related characteristics. Absence or presence of disability among patients with lepromatous leprosy was evaluated at the same time. Results The overall mean DLQI score for lepromatous leprosy (18.78) was higher than that for control (9.00) (P < 0.001). Patients with lepromatous leprosy scored significantly higher for all items (P < 0.001) except Q4 (clothes choice). Controls scored significantly lower for all domains of DLQI. Scores of LL increased markedly with increasing clinical severity, but were not associated with educational level, gender, age and disease duration. The inter‐item correlation averaged 0.240 and Cronbach’s alpha was 0.759, indicating high internal consistency. Conclusions This is the first exclusive study to attempt to measure the impact of lepromatous leprosy on QoL. Lepromatous leprosy has a severe impact on QoL.     

Antibody-based enzyme-linked immunosorbent assay for determination of anti-PGL-I specific circulating immune complex in leprosy patients

A serological study was performed in 122 individuals: 75 leprosy patients and 47 healthy controls. The ELISA test was performed for IgG and IgM using the glycolipid PGL-I antigen from Mycobacterium leprae. Circulating immune complexes (CIC) were isolated by PEG 6000 precipitation method and after dissociation with an acid solution, the IgG and IgM specific against PGL-I were tested with the ELISA test. The multibacillary patients had high levels of antibodies, compared with paucibacillary patients and controls. The antibodies isolated from the CIC presented a similar spectrum spectral distribution as the serology. A positive correlation between the levels of free and CIC bound antibodies was observed. In contrast with tuberculosis patients, specific antibodies present in CIC were not responsible for false-negative results found in some multibacillary patients' serology, since no or very low levels of specific antibodies were found in PEG precipitated serum of these patients. No relation was observed with specific antibody levels detected in CIC during leprosy reactions.     

界线类偏瘤型麻风伴I型麻风反应一例

患者,男,27岁。全身水肿性红斑、斑丘疹伴痛,高热1周。组织液抗酸染色查菌BI 3.40。组织病理检查示：表皮变薄,表真皮间无浸润带,真皮内成团淋巴细胞、组织细胞、泡沫细胞等浸润,累及脂肪层和附属器。2年前患者曾诊断为BL麻风,抗麻风联合化疗治疗1年。     

Effect of unique Mycobacterium leprae phenolic glycolipid-I (PGL-I) on tumour necrosis factor production by human mononuclear cells

Mycobacterium leprae cell wall-associated components are found in large amounts in the tissues of leprosy patients, particularly those at the lepromatous pole. Among these molecules, the phenolic glycolipid-I (PGL-I), unique to M. leprae, has been involved in the selective anergy observed in the lepromatous patients. Armadillo-derived M. leprae retains only a small proportion of the total PGL-I found in infected tissues. Therefore, the addition of PGL-I to M. leprae in vitro is important for a better understanding of M. leprae effects in vivo. We have studied the influence of PGL-I on TNF production by normal human peripheral blood mononuclear cells (PBMC) and by a human monocytic leukaemia cell line (THP-1) following stimulation with killed M. leprae. PGL-I alone did not induce TNF secretion by PBMC, but when associated with a sub-optimal dose of armadillo-derived M. leprae increased the release of this cytokine. In agreement with these results, M. leprae-exposed THP-1 cells did not secrete detectable levels of TNF unless PGL-I was simultaneously added to the culture. This increase in TNF production suggests that PGL-I plays a role in the induction of TNF during the natural infection. In addition, the modulatory effect of PGL-I on TNF release by THP-1 cells reinforces that monocytes are one of the possible targets of this molecule.     

瘤型麻风六例临床分析

对2014-2017年发现的6例瘤型麻风患者进行回顾性分析.6例瘤型麻风均有典型的症状体征及病理特征,其中男3例,女3例,年龄30～60岁,病史1个月～40年.皮损类型主要为结节、丘疹.面部均累及,累及四肢的有4例,累及躯干的有2例.4例患者有神经受累现象,1例出现肢体疼痛,1例出现右下肢反复溃疡.组织病理学符合瘤型麻...     

SLE患者皮质类固醇治疗前后血清IL－2和TNF－α水平的比较

ＳＬＥ患者皮质类固醇治疗前后血清ＩＬ－２和ＴＮＦ－α水平的比较刘国英①瞿国伟②ＳＬＥ是一种以免疫调节异常为特征的自身免疫性疾病，而免疫调节主要是通过多种细胞因子相互作用实现的。因此，研究ＳＬＥ病人细胞因子变化将有助于阐明该病的发病机理，我们检测了１４...     

LOCALIZED LEPROMATOUS LEPROSY AND ITS RESPONSE TO CHEMO-IMMUNOTHERAPY

Background. This is an unusual presentation of lepromatous leprosy (ll ) in a young boy, 12 years of age. The study forms part of a large scale immunotherapeutic trial with Mycobacterium w (M.w) antileprosy vaccine. The trial is being conducted in two major hospitals in New Delhi, India. Materials and Methods. This patient presented with three lesions: one on each forearm and the third on the left leg. He was classified initially as borderline tuberculoid leprosy. Slit-skin smears and histopathology from the lesions proved the diagnosis to be lepromatous leprosy with a bacterial index (bi ) 6+. The initial lepromin test was negative. The patient was treated with chemo-immunotherapy (standard multidrug therapy and immunotherapy with Mycobacterium w vaccine). Results. Investigations after 1 year (15 months) of multidrug therapy and three doses of vaccine, showed a remarkable fall in the bi from 6 to 0 in the lesions, a lepromin positivity of 5 mm, and a histological upgrading from lepromatous leprosy to borderline tuberculoid. Immunologic studies at 15 months revealed a good LTT response and high levels of cytokines, specifically IL-2 and IFN-γ. Conclusions. This report presents an LL patient with disease limited to a few sites. It stresses the importance of slit-smear and biopsy in all patients of leprosy, and it highlights the upgrading observed on administration of chemo-immunotherapy.     

误诊为系统性红斑狼疮的瘤型麻风一例

报告1例女性瘤型麻风.患者女,39岁,因多关节痛,面部及上肢酱红色丘疹,斑块半年就诊,伴有光敏,发热及乏力.实验室检查:尿蛋白强阳性、血红蛋白 97g/L,血小板51 × 109/L,补体C3为560 mg/L(850～1930 mg/L)、C4为103 mg/L( 120～360 mg/L)、ANA 1:160阳性.符合系统性红斑狼疮诊断条件,给予泼尼松50 mg/d、沙利度按100 mg/d及羟氯喹200 mg/d,治疗后系统症状改善,但皮损进行性加重,两年后逐渐出现上腭及鼻中隔穿孔等病变.最终经组织病理检查及抗酸染色确诊为瘤型麻风.提示瘤型麻风可以出现多系统损害,自身抗体阳性,必须警惕误诊为风湿性疾病.     

麻风病血清流行病学调查与化学预防的实施

目的:评价化学预防的保护性,本研究依据血清流行病学调查,对两个麻风病高流行村麻风病接触者和一般人群实施利福平化学预防.方法:采用临床查体、检测血清酚糖脂-1(PGL-Ⅰ)抗体和鼻分泌物麻风菌,了解人群的麻风菌感染状况,为评价预防治疗效果提供科学依据.结果:YG村临床普查率达98%,发现早期病人2例;接触者血清PGL-Ⅰ抗体阳性率76%,麻风菌鼻携带率35%,预防服药率达98%.HG村临床普查率91%,发现早期病人1例,人群血清PGL-Ⅰ抗体受检率54%,其中血清PGL-Ⅰ抗体阳性率33%,服药率达85%.结论:对亚临床感染率较高的人群实施化学预防很有必要.预防后的发病率与血清学等实验室数据可为评价预防治疗提供依据.     

麻风免疫诊断进展

本文系统地复习了麻风杆菌(ML)基因组诠释前后的免疫诊断研究,诠释前的研究主要包括以PGL-I为基础的血清学实验和以蛋白抗原为基础的血清学实验,诠释后的研究主要介绍了培养滤液蛋白CFP-10和早期分泌抗原在免疫诊断中的应用,还介绍了特异性引起T细胞反应的肽类的研究。