Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
PLoS Negl Trop Dis. 2011 Dec;5(12):e1327. doi: 10.1371/journal.pntd.0001327. Epub 2011 Dec 13.
Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions.
METHODOLOGY/PRINCIPAL FINDINGS: TNF-α, TGF-β and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68 macrophage cell marker and S100.
CONCLUSIONS/SIGNIFICANCE: Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-β in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-β were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-β detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an association of iNOS and TGF-β with T1R.
以前研究细胞因子在麻风病发病机制中的作用的研究，或者只针对少数患者进行，或者没有结合临床和组织学数据。INFIR 队列研究是对 303 例新的多菌型麻风病患者进行的前瞻性研究，旨在确定反应和神经损伤的危险因素。本研究采用光镜和免疫组织化学技术对皮肤和神经活检中的细胞浸润进行特征描述，以确定细胞因子标志物、神经和细胞标志物与麻风反应之间的任何关联。
方法/主要发现：在招募时，使用单克隆抗体检测免疫组织化学技术检测了 299 例皮肤活检和 68 例神经活检中皮肤和神经活检中 TNF-α、TGF-β 和 iNOS 蛋白。组织用苏木精和伊红、改良 Fite Faraco、CD68 巨噬细胞细胞标志物和 S100 染色。
结论/意义：活检的组织学分析显示，43%为边界结核样（BT）麻风，27%为边界瘤型麻风，9%为瘤型麻风，13%为不确定型麻风，7%无炎症。46%有 1 型反应（T1R）的组织学证据，10%有结节性红斑麻风。在 232 例皮肤活检中，78%（181/232）检测到 TNF-α，78%检测到 iNOS，94%检测到 TGF-β。在 BT 麻风患者中，这三种分子的水平均较高。TNF-α定位于肉芽肿中的巨噬细胞和上皮样细胞、表皮和真皮神经中的少数病例中。TNF-α、iNOS 和 TGF-β 均与 T1R 显著相关（p<0.001）。分析了 68 例神经活检。在 88%、38%和 28%的活检中分别检测到 CD68、TNF-α和 iNOS 染色。免疫组织化学检测到的三种细胞因子 TNF-α、iNOS 和 TGF-β 与皮肤反应的存在有显著相关性。本研究首次证明 iNOS 和 TGF-β 与 T1R 相关。
