STREPTOCOCCAL AND STAPHYLOCOCCAL TOXINS IN HENOCH-SCHOLEIN PURPURA

过敏性紫癜中的链球菌和葡萄球菌毒素

• 批准号: 6114203
• 负责人: TERRI FINKEL
• 金额: $ 3.22万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6114203
• 关键词: IgA nephropathy; Streptococcus; T lymphocyte; biopsy; child (0-11); clinical research; exotoxins; human subject; pathologic process; purpura; staphylococcal exotoxin

Ten children with HSP have been studied. Eight of the 10 children were cultured from the nose, throat and rectum for staphylococcus aureas (SA) and Group A beta hemolytic streptococcus (GAS) at presentation. In some of these 8 children, anti-streptococcus antibodies and/or a rapid strep assay were also done. Cultures from 5 of 8 children were positive for SA (4) or GAS (1). In 2 of 5 children, cultures were positive for SA from all 3 sites. In 2 of 8 children with negative cultures, there was other evidence of GAS (anti-strep antibodies or rapid strep positivity). Thus, 7 of 8 children with HSP had evidence of infection with SA or GAS at the time of presentation. The SA isolates from 2 of the 4 children have been analyzed for toxin production. (The other 2 are pending). One isolate was positive for TSST-1 by PCR and the second isolate was positive for both TSST-1 and SEA. Three patients had a normal CD4 and CD8 T cell Vbeta repertoire in peripheral blood, while 7 had abnormalities noted, in particular in the Vbeta 2 and 3 subsets, when compared to healthy controls. AC, TW, and LM showed elevations of CD4 and CD8 Vbeta 3.1, while CR and CP showed elevations of Vbeta 3.1 only in the CD4 subset. LM showed the elevation of Vbeta 3.1 on 2 independent samples drawn 3 weeks apart. In CR, the elevation of Vbeta 3.1 returned to normal, coincident with clinical resolution of HSP and negative cultures. A skin biopsy done of LM's HSP rash showed early leucocytoclastic vasculitis, IgA, C3, fibrin present within blood vesself of the superficial dermis, consistent with HSP. Vbeta analysis showed an elevation of Vbeta 3, compared to healthy control peripheral blood, and, interestingly, a significant elevation compared to LM's peripheral blood. KT showed an elevation of CD4 Vbeta 2. In contrast, LM and AR showed an abnormally low level of CD4 Vbeta 2. Interestingly, while LM showed this low level of Vbeta 2 in the 2 independent samples drawn 3 weeks apart, a sample assayed almost 2 years later (~ 1 year post-remission) showed normal levels of CD4 Vbeta 2. In conclusion, these preliminary data confirm and extend earlier anecdotal data showing an association between infection and HSP. While GAS, in particular, has been associated with HSP (in about 30% of patients), these data suggest that SA may actually show a stronger association (>60% of patients). These data also suggest HSP-associated Vbeta repertoire changes in peripheral blood and involved skin. Of course, these analyses were done on only a few patients and without disease controls. We do not understand the differences between the patients with and without Vbeta abnormalities. In particular, we do not at this time have the requisite bacteriologic or toxin data in order to draw conclusions regarding Vbeta repertoire changes and particular bacterial exotoxins. However, these data lead us to hypothesize that bacterial toxins may play a role in the pathogenesis of HSP, to suggest that children with HSP be thoroughly cultured for SA as well as GAS, and to advocate clinical trials of aggressive antibiosis in children with HSP.

对 10 名患有 HSP 的儿童进行了研究。 10 名儿童中的 8 名在就诊时从鼻子、喉咙和直肠进行了金黄色葡萄球菌 (SA) 和 A 组 β 溶血性链球菌 (GAS) 培养。在这 8 名儿童中的一些中，还进行了抗链球菌抗体和/或快速链球菌检测。 8 名儿童中有 5 名的培养物呈 SA (4) 或 GAS (1) 阳性。在 5 名儿童中，有 2 名的所有 3 个地点的培养物均呈 SA 阳性。在 8 名培养阴性的儿童中，有 2 名存在其他 GAS 证据（抗链球菌抗体或快速链球菌阳性）。因此，8 名 HSP 儿童中有 7 名在就诊时有 SA 或 GAS 感染的证据。已对 4 名儿童中 2 名的 SA 分离株进行了毒素产生分析。 （其他 2 个待定）。通过 PCR 检测，一株分离株呈 TSST-1 阳性，而另一株株则呈 TSST-1 和 SEA 阳性。与健康对照相比，3 名患者外周血中 CD4 和 CD8 T 细胞 Vbeta 库正常，而 7 名患者发现异常，特别是 Vbeta 2 和 3 亚群。 AC、TW 和 LM 显示 CD4 和 CD8 Vbeta 3.1 升高，而 CR 和 CP 仅在 CD4 子集中显示 Vbeta 3.1 升高。 LM 显示 2 个相隔 3 周抽取的独立样本的 Vbeta 3.1 升高。在 CR 中，Vbeta 3.1 的升高恢复正常，与 HSP 和阴性培养物的临床消退一致。对 LM 的 HSP 皮疹进行的皮肤活检显示早期白细胞破碎性血管炎，真皮浅层血管内存在 IgA、C3、纤维蛋白，与 HSP 一致。 Vbeta 分析显示，与健康对照外周血相比，Vbeta 3 升高，有趣的是，与 LM 外周血相比，Vbeta 3 显着升高。 KT 显示 CD4 Vbeta 2 升高。相比之下，LM 和 AR 显示 CD4 Vbeta 2 异常低水平。有趣的是，虽然 LM 在相隔 3 周抽取的 2 个独立样本中显示出如此低的 Vbeta 2 水平，但检测的样本几乎2 年后（缓解后约 1 年）显示 CD4 Vbeta 2 水平正常。总之，这些初步数据证实并扩展了显示感染与 HSP 之间关联的早期轶事数据。虽然 GAS 尤其与 HSP 相关（约 30% 的患者），但这些数据表明 SA 实际上可能表现出更强的关联（>60% 的患者）。这些数据还表明外周血和受累皮肤中与 HSP 相关的 Vbeta 谱系发生变化。当然，这些分析仅针对少数患者进行，并且没有疾病控制。我们不了解有和没有 Vbeta 异常的患者之间的差异。特别是，我们目前没有必要的细菌学或毒素数据来得出有关 Vbeta 库变化和特定细菌外毒素的结论。然而，这些数据使我们推测细菌毒素可能在 HSP 的发病机制中发挥作用，建议对 HSP 儿童进行彻底的 SA 和 GAS 培养，并提倡对 HSP 儿童进行积极的抗生素临床试验。