The mycobacterial 65 kD heat-shock protein and autoimmune arthritis

Summary Arthritis — induced experimentally in rats by immunization with mycobacteria has been shown to depend on specific T cell recognition of an epitope present on the mycobacterial 65-kD heat-shock protein. This particular epitope has been observed to have a structural mimicry with a cartilage-associated molecule present in the joints. Since the bacterial heat-shock proteins and the cartilage-associated molecules are of a conserved nature, one might infer from the experimental model that in humans similar mimicry could play a role in the initiation of autoimmune arthritis. Recent findings from the analysis of immunological reactivity to the 65-kD in rheumatoid arthritis patients seem to support such a role for the mycobacterial 65-kD heat-shock protein in human disease.     

Diagnosis and treatment of nontuberculous mycobacterial pulmonary diseases: a Korean perspective

The incidence of pulmonary disease caused by nontuberculous mycobacteria (NTM) appears to be increasing worldwide. In Korea, M. avium complex and M. abscessus account for most of the pathogens encountered, whilst M. kansasii is a relatively uncommon cause of NTM pulmonary diseases. NTM pulmonary disease is highly complex in terms of its clinical presentation and management. Because its clinical features are indistinguishable from those of pulmonary tuberculosis and NTMs are ubiquitous in the environment, the isolation and identification of causative organisms are mandatory for diagnosis, and some specific diagnostic criteria have been proposed. The treatment of NTM pulmonary disease depends on the infecting species, but decisions concerning the institution of treatment are never easy. Treatment requires the use of multiple drugs for 18 to 24 months. Thus, treatment is expensive, often has significant side effects, and is frequently not curative. Therefore, clinicians should be confident that there is sufficient pathology to warrant prolonged, multidrug treatment regimens. In all of the situations, outcomes can be best optimized only when clinicians, radiologists, and laboratories work cooperatively.     

Mycobacterium kansasii pulmonary diseases in Korea

Mycobacterium kansasii is one of the most common cause of pulmonary diseases due to nontuberculous mycobacteria. We investigated the changing in the number of isolation of M. kansasii and the clinical characteristics of M. kansasii pulmonary disease in Korea. Through searching the database of the Korean Institute of Tuberculosis, we identified the cases of isolated M. kansasii from 1992 to 2002. The number of M. kansasii isolation had increased from once in 1992 to 62 in 2002. Fifteen patients with M. kansasii pulmonary disease were identified during the period January 1997 to December 2002. Twelve patients (80%) were male and fourteen (93%) were from highly industrialized areas. The most common symptom was a cough. Seven patients (47%) had a cavitary lesion and right upper lobe was most commonly involved. Patients responded well to isoniazid and rifampicin based regimens both bacteriologically and radiographically. In conclusion, M. kansasii isolation has increased, especially in highly industrialized areas, as well as other nontuberculous mycobacteria in Korea.     

耐异烟肼结核杆菌KatG463condon点突变的分子信标快速检测

目的应用分子信标探针检测结核杆菌耐异烟肼kat G463condon点突变,并与测序结果比较以验证该检测方法。方法运用软件对Beacondesigner设计,katG基因包含463condon的分子信标,建立其扩增体系及分子信标芯片检测方法;对扩增产物测序并作比较。结果通过CDC相机观测到结核标准株及耐异烟肼PCR产物与分子信标杂交后荧光信号区别明显;16株耐异烟肼组与10株H37RV标准株对照组荧光信号强度比较,耐异烟肼组463condon突变检出率为37％,分子信标检测方法与测序法符合率达93％。结论分子信标技术是一种具有高灵敏核酸点突变检测技术;分子信标芯片检测方法与测序法符合率较好。     

Positive QuantiFERON test and the severity of COVID-19 disease: A prospective study

BackgroundA strong negative correlation is reported between the Bacille Calmette Guerin (BCG) index and COVID-19 mortality. The present study explored if frequent exposure to strong Th1 antigens like Mycobacteria or Salmonella have any effect on the progression of the disease in COVID-19 patients.MethodsThis prospective comparative study comprised of 3 groups of 20 each of mild or asymptomatic COVID-19 patients (A), severely ill patients (S) and healthy volunteers with a COVID Negative report (H).ResultsQuantiFERON TB Gold (QFT) which is interferon gamma release assay (IGRA) against Mtb antigen was used to quantify immunity status of patients against the tuberculosis. Group S showed positive QFT in only 15% patients as against 50% QFT positive patients in group A and H. All fourteen patients in group S with QFT negative report died while 5 of six survived patients showed positive QFT report either on initial or repeat testing done at 6 weeks. The sixth survived patient was QFT negative but showed high antibody titre against H antigen (TH) on Widal test. All severely ill group S patients showed huge reduction of IGRA even to the mitogen stimulus thus suggesting gross general unresponsiveness of T cells. Presence of BCG scar showed no correlation with prevalence or progression of the disease.ConclusionPopulation in an endemic area of tuberculosis and typhoid with good community exposure to these antigen is likely to withstand COVID -19 better and show reduced mortality following it.     

La lèpre,pilier de la génétique des maladies infectieuses

Despite a natural reservoir of Mycobacterium leprae limited to humans and free availability of an effective antibiotic treatment, more than 200,000 people develop leprosy each year. This disease remains a major cause of disability and social stigma worldwide. The cause of this constant incidence is currently unknown and indicates that important aspects of the complex relationship between the pathogen and its human host remain to be discovered. An important contribution of host genetics to susceptibility to leprosy has long been suggested to account for the considerable variability between individuals sustainably exposed to M. leprae. Given the inability to cultivate M. leprae in vitro and in the absence of relevant animal model, genetic epidemiology is the main strategy used to identify the genes and, consequently, the immunological pathways involved in protective immunity to M. leprae. Recent genome-wide studies have identified new pathophysiological pathways which importance is only beginning to be understood. In addition, the prism of human genetics placed leprosy at the crossroads of other common diseases such as Crohn's disease, asthma or myocardial infarction. Therefore, novel lights on the pathogenesis of many common diseases could eventually emerge from the detailed understanding of a disease of the shadows.     

Repurposing of the gold drug auranofin and a review of its derivatives as antibacterial therapeutics

Multidrug resistance (MDR) is a significant issue associated with the clinical application of antibiotics. It is also challenging to discover and develop new antibiotics with novel scaffolds. Therefore, the repurposing of existing drugs has become a promising strategy for antibiotic drug discovery. Auranofin, an approved gold metallic drug, has been used for the treatment of rheumatoid arthritis (RA) for many years. Recent research revealed that auranofin has strong antibacterial activity against multiple Gram-positive bacteria by inhibiting thioredoxin reductase (TrxR). These results inspired the development of gold complexes as antibacterial agents. Herein, we discuss recent advances in the development of auranofin and other gold complexes as antibacterial agents, providing a new viewpoint for the treatment of bacterial infection.     

Dressed not to kill: CD16+ monocytes impair immune defence against tuberculosis

Monocytes are blood leukocytes that can differentiate into several phagocytic cell types, including DCs, which are instrumental to the inflammatory response and host defence against microbes. A study published in this issue of the European Journal of Immunology by Balboa et al. [Eur. J. Immunol. 2013. 43: 335‐347] suggests that a shift of the CD16^? monocyte population toward a CD16⁺ subpopulation may represent an immune evasion strategy that ultimately favors persistence of Mycobacterium tuberculosis. Together with other recent reports, the article by Balboa et al. sheds new light on the function of CD16⁺ monocytes in health and disease; in this commentary, we discuss the implications stemming from these findings.