Laboratory of Dermatology and Immunodeficiencies, Medical School of the University of São Paulo, São Paulo, Brazil.
J Eur Acad Dermatol Venereol. 2012 Mar;26(3):319-24. doi: 10.1111/j.1468-3083.2011.04067.x. Epub 2011 May 30.
Infliximab and etarnecept are now widely used for treating severe psoriasis. However, these drugs, especially infliximab, increased the risk of tuberculosis reactivation. Surprisingly, epidemiological data suggest that the tuberculosis rate in patients taking infliximab in São Paulo State, Brazil, is similar to that of some developed, non-endemic countries.
The aim of this study was to better understand the effect of infliximab on Mycobacterium tuberculosis (Mtb) immune responses of psoriasis patients in an endemic setting (Brazil).
We evaluated the tuberculosis-specific immune responses of severe psoriasis patients and healthy individuals, both tuberculin skin test (TST) positive, in the presence/absence of infliximab. Patients had untreated severe psoriasis, no co-morbidities affecting the immune responses and a TST >10 mm. Healthy TST(+) (>10 mm) individuals were evaluated in parallel. PBMC cultures from both groups were stimulated with different Mycobacterium tuberculosis (Mtb) antigens (ESAT-6, 85B and Mtb lysate) and phytohemagglutinin, with or without infliximab (5 μg/mL). Parameters evaluated were TNF-α, IFN-γ and IL-10 secretion by ELISA, overnight IFN-γ ELISpot and lymphocyte proliferative response (LPR).
Infliximab almost abolished TNF-α detection in PBMC supernatants of both groups. It also significantly reduced the LPR to phytohemagglutinin and the Mtb antigens as well as the IFN-γ levels secreted into day 5 supernatants in both groups. There was no concomitant exaggerated IL-10 secretion that could account for the decreases in these responses. ELISpot showed that, contrasting with the central-memory responses above, infliximab did not affect effector-memory INF-γ-releasing T-cell numbers.
Infliximab affected some, but not all aspects of the in vitro antituberculosis immune responses tested. The preserved effector-memory responses, putatively related to exposure to environmental mycobacteria, may help to explain the lower than expected susceptibility to tuberculosis reactivation in our setting.
英夫利昔单抗和依那西普现在被广泛用于治疗严重的银屑病。然而，这些药物，尤其是英夫利昔单抗，增加了结核分枝杆菌（Mycobacterium tuberculosis，Mtb）再激活的风险。令人惊讶的是，流行病学数据表明，在巴西圣保罗州使用英夫利昔单抗的患者中，结核病的发生率与一些发达的非流行国家相似。
本研究旨在更好地了解英夫利昔单抗在巴西流行地区对银屑病患者 Mtb 免疫反应的影响。
我们评估了严重银屑病患者和健康个体的结核分枝杆菌（Mycobacterium tuberculosis，Mtb）特异性免疫反应，这些患者均为结核菌素皮肤试验（Tuberculin skin test，TST）阳性，且存在/不存在英夫利昔单抗。患者患有未经治疗的严重银屑病，无影响免疫反应的合并症，且 TST > 10mm。同时评估了健康的 TST（+）（>10mm）个体。用不同的 Mtb 抗原（ESAT-6、85B 和 Mtb 裂解物）和植物血凝素刺激两组的 PBMC 培养物，同时加入或不加入英夫利昔单抗（5μg/mL）。通过 ELISA 检测 TNF-α、IFN-γ 和 IL-10 的分泌，进行 overnight IFN-γ ELISpot 和淋巴细胞增殖反应（Lymphocyte proliferative response，LPR）。
英夫利昔单抗几乎消除了两组 PBMC 上清液中 TNF-α的检测。它还显著降低了植物血凝素和 Mtb 抗原的 LPR 以及两组第 5 天上清液中 IFN-γ的水平。没有同时发生过度的 IL-10 分泌，这可以解释这些反应的下降。ELISpot 显示，与上述中央记忆反应相反，英夫利昔单抗不影响效应记忆 INF-γ释放 T 细胞的数量。
英夫利昔单抗影响了所测试的体外抗结核免疫反应的一些方面，但不是所有方面。保留的效应记忆反应，可能与暴露于环境分枝杆菌有关，这可能有助于解释我们的环境中结核病再激活的发生率低于预期。
