Moraes M F, Ordway D, Oliveira L, Costa I L, Badura R, Pinheiro M N, da Graça J M, Ventura F A
Serviço de Medicina II, Hospital de Egas Moniz.
Rev Port Cardiol. 1999 Apr;18(4):359-67.
Takayasu's arteritis (TA) is a disease of unknown aetiology, characterized histologically by an inflammatory cell infiltrate that affects all layers of the arterial wall. Its association with tuberculosis (TB) was described 50 years ago, based on the presence of Langhan's giant cells and granulomas similar to those found in tuberculous lesions. The presence of TB in patients with TA well as been reported in several studies as well as a positive tuberculous response, but these associations could be fortuitous in countries where TB is endemic. Recent studies have shown that patients with TA have a heightened humoral response to mycobacterial antigens including the 65 kDa fraction, a heat shock protein (HSP) that has also been found to be expressed in the arterial wall of patients with TA. The purpose of this study was to determine lymphoproliferative response and interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) stimulated by live Mycobacterium tuberculosis (Mtb) H37Rv and a panel of mycobacterial antigens, in the hope of contributing to a better understanding of the cellular immune responses to Tuberculosis in Takayasu's arteritis.
Standard lymphoproliferation tests and IFN-gamma determination (ELISA) were performed in a 47-year old black man who fulfilled criteria for TA and 10 healthy controls, BCG vaccinated, Mantoux positive. The following were used: Mtb H37Rv, Purified Protein Derivative (PPD), purified 30 kDa, recombinant M. bovis BCG 10 kDa, 38 kDa, 65 kDa, 70 kDa, Short Term-Culture Filtrate Proteins (ST-CFP), Mid Term-Culture Filtrate Proteins (MT-CFP) obtained from H37Rv and phytohemaglutinin (PHA) as mitogen for positive control.
PBMC from the patient with TA when compared to the mean values of the 10 healthy donors showed decreased proliferation in response to all antigens, with the exception of 65 kDa. The TA patient showed a similar pattern of IFN-gamma production to that obtained with control donors, with the exception of higher IFN-gamma production in response to ST-CFP and MT-CFP.
We have shown reactivity of peripheral lymphocytes to HSP 65 kDa and a trend towards higher production of IFN-gamma in response to ST-CFP and MT-CFP in a patient with TA. These facts, together with the already established heightened humoral response, strengthens the association between TB and TA. However, HSP 65 kDa is not specific to TB and we conclude that similar studies using lymphocytes obtained from the arterial wall of TA patients may help to clarify the role of mycobacterial infection in Takayasu's arteritis.
高安动脉炎（TA）是一种病因不明的疾病，组织学特征为炎症细胞浸润，累及动脉壁各层。50年前就有人描述其与结核病（TB）的关联，依据是存在朗汉斯巨细胞和类似于结核病变中发现的肉芽肿。多项研究报告了TA患者中存在结核病以及结核菌素反应呈阳性，但在结核病流行的国家，这些关联可能是偶然的。最近的研究表明，TA患者对包括65 kDa组分在内的分枝杆菌抗原的体液反应增强，65 kDa组分是一种热休克蛋白（HSP），也已发现在TA患者的动脉壁中表达。本研究的目的是确定经活结核分枝杆菌（Mtb）H37Rv和一组分枝杆菌抗原刺激后外周血单个核细胞（PBMC）的淋巴细胞增殖反应和干扰素-γ（IFN-γ）产生情况，以期有助于更好地理解高安动脉炎中对结核病的细胞免疫反应。
对一名符合TA标准的47岁黑人男性和10名接种卡介苗、结核菌素试验阳性的健康对照者进行标准淋巴细胞增殖试验和IFN-γ测定（ELISA）。使用了以下物质：Mtb H37Rv、纯化蛋白衍生物（PPD）、纯化的30 kDa、重组牛分枝杆菌卡介苗10 kDa、38 kDa、65 kDa、70 kDa、短期培养滤液蛋白（ST-CFP）、从中期培养滤液中获得的中期培养滤液蛋白（MT-CFP）以及作为阳性对照的促有丝分裂原植物血凝素（PHA）。
与10名健康供体的平均值相比，TA患者的PBMC对除65 kDa外的所有抗原的增殖反应均降低。TA患者的IFN-γ产生模式与对照供体相似，但对ST-CFP和MT-CFP的IFN-γ产生较高。
我们已证明一名TA患者的外周淋巴细胞对HSP 65 kDa有反应，且对ST-CFP和MT-CFP有产生较高IFN-γ的趋势。这些事实，连同已确定的增强的体液反应，加强了结核病与TA之间的关联。然而，HSP 65 kDa并非结核病所特有，我们得出结论，使用从TA患者动脉壁获得的淋巴细胞进行类似研究可能有助于阐明分枝杆菌感染在高安动脉炎中的作用。
