里斯本耐多药结核病的爆发：通过限定性片段长度多态性分析发现

背景1996～1997年,里斯本各医院的主要人类免疫缺陷病毒(HIV)血清阳性的病人中发生的耐性多药结核病(MDR-TB)。目的在里斯本市的几家医院,包括一家监狱医院,发现耐多药结核病(MDR-TB)的传播与爆发流行。设计用限定性片段长度多态性(RFLP)检测耐异烟肼、利福平和其他一种药物的结核分枝杆菌菌株的指纹。结果共43个MDR-TB菌株被分型。HIV阳性病人占67％,HⅣ阴性病人占12％,其他病人的HIV情况未知。大约88％的菌株属于3种基因特征相似的簇,揭示可能是最近的传播。一个主要簇(A簇)的菌株占72％的病例,其中45％的病例来自监狱医院。这些簇的菌株对异烟肼、利福平、链霉素以及有时对乙胺丁醇耐药。对A簇的所有病人进行了回顾性的流行病学调查,以便探讨病例之间的流行病学联系。结论结果表明,最近在里斯本医院的MDR-TB传播,主要发生在HIV阳性病人。此外,主要的MDR-TB簇菌株并非局限于HIV感染的个体,这些菌株在一些有免疫力的病人中也被分离出来。     

Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage,Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil

We recently detected the spoligotype patterns of strains of Mycobacterium pinnipedii, a species of the Mycobacterium tuberculosis complex, in sputum samples from nine cases with pulmonary tuberculosis residing in Porto Alegre, South Brazil. Because this species is rarely encountered in humans, we further characterized these nine isolates by additional genotyping techniques, including 24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) typing, verification of the loci TbD1, RD9, pks15/1, RD^Rio, and fbpC, the insertion of IS6110 at a site specific to the M. tuberculosis Latin American Mediterranean (LAM) lineage, and whole-genome sequencing. The combined analysis of these markers revealed that the isolates are in fact M. tuberculosis and more specifically belong to the LAM genotype. Most of these isolates (n = 8) were shown to be multidrug resistant (MDR), which prompted us to perform partial sequencing of the rpoA, rpoB, rpoC, katG, and inhA genes. Seven isolates (77.8%) carried the S315T mutation in katG, and one of these (11%) also presented the C(−17)T single-nucleotide polymorphism (SNP) in inhA. Interestingly, six of the MDR isolates also presented an undescribed insertion of 12 nucleotides (CCA GAA CAA CCC) in codon 516 of rpoB. No putative compensatory mutation was found in either rpoA or rpoC. This is the first report of an M. tuberculosis LAM family strain with a convergent M. pinnipedii spoligotype. These spoligotypes are observed in genotype databases at a modest frequency, highlighting that care must be taken when identifying isolates in the M. tuberculosis complex on the basis of single genetic markers.     

Renal transplant patients show variations in their self-reactive repertoires: a serial study

We addressed the question of whether allo-transplantation (Tx) induces breakdown of tolerance to self-antigens or alteration of the autoreactive T cell repertoire in humans. The serial variation of T cell autoreactivity was studied in the peripheral blood of 12 renal transplant patients, by autologous limiting dilution assay and autologous mixed lymphocyte reaction. Ten of 12 patients presented a positive response in autologous peripheral blood mononuclear cells in the post-Tx period, in contrast to four of 12 patients before Tx (P = 0.038). Multi-hit kinetics was found in 57% of the assays analyzed, indicating frequent regulatory control of the autologous response. Quantitative analysis performed in eight patients showed an increase in precursor frequency at >1 year post-Tx in five patients. These data indicate that autoreactivity increases or develops following Tx, in humans. Post-Tx events such as alloreactivity, infections or immunosuppression could interfere with the balance of autoreactive and regulatory cells, leading to changes in the T cell repertoires to self-antigens and eventually breakdown of self-tolerance. Further investigation is needed to elucidate whether post-Tx autoreactivity contributes to rejection, plays a regulatory role over alloreactivity or both, at separate times.