Scollard David M, Chaduvula Meher V, Martinez Alejandra, Fowlkes Natalie, Nath Indira, Stryjewska Barbara M, Kearney Michael T, Williams Diana L
National Hansen's Disease Programs, 1770 Physician Park Dr., Baton Rouge, LA 70816, USA.
Clin Vaccine Immunol. 2011 Jun;18(6):947-53. doi: 10.1128/CVI.00042-11. Epub 2011 Apr 20.
Type 1 reaction (T1R) is a systemic inflammatory syndrome causing substantial morbidity in leprosy. T1R results from spontaneously enhanced cellular immunity in borderline types of leprosy, but there are no established laboratory markers for the reaction. Preliminary studies have identified elevated circulating CXC ligand 10 (CXCL10) during T1R. Correlation of CXCL10 with clinical T1R was studied in repeated serum specimens obtained before, during, and after T1R. CXCL10 gene expression was assessed in biopsy specimens taken before and during T1R, and sections were stained for the cytokine using monoclonal antibodies. Sequential serum specimens revealed elevation of circulating CXCL10 associated with episodes of T1R (P = 0.0001) but no evidence of an earlier, predictive change in the level of the chemokine. Reverse transcriptase (RT)-PCR revealed elevated expression of CXCL10 transcripts during T1R, but not in patients who did not have T1R. No significant correlation between CXCL10 and gamma interferon (IFN-γ) mRNA levels was observed. Immunohistochemical staining of the skin biopsy specimens suggested an overall increase in CXCL10 but did not identify a particular strongly staining population of leukocytes. Increased CXCL10 in lesions and serum is characteristic of T1R. CXCL10 measurement offers new possibilities for laboratory diagnosis and monitoring of T1R. Studies of the regulation of CXCL10 may provide insight into the mechanisms of T1R and identify potential new drug targets for treatment.
1型反应(T1R)是一种全身性炎症综合征,在麻风病中可导致严重发病。T1R是由麻风病边缘型的细胞免疫自发增强引起的,但目前尚无该反应的既定实验室标志物。初步研究已确定在T1R期间循环中的CXC配体10(CXCL10)升高。在T1R之前、期间和之后获取的重复血清标本中研究了CXCL10与临床T1R的相关性。在T1R之前和期间采集的活检标本中评估了CXCL10基因表达,并使用单克隆抗体对细胞因子进行切片染色。连续血清标本显示,循环中的CXCL10升高与T1R发作相关(P = 0.0001),但没有证据表明趋化因子水平有早期预测性变化。逆转录酶(RT)-PCR显示在T1R期间CXCL10转录本表达升高,但在未发生T1R的患者中未升高。未观察到CXCL10与γ干扰素(IFN-γ)mRNA水平之间存在显著相关性。皮肤活检标本的免疫组织化学染色表明CXCL10总体增加,但未识别出特定的强染色白细胞群体。病变和血清中CXCL10升高是T1R的特征。CXCL10检测为T1R的实验室诊断和监测提供了新的可能性。对CXCL10调控的研究可能有助于深入了解T1R的机制,并确定潜在的新治疗药物靶点。