Weyand C M, Tetzlaff N, Björnsson J, Brack A, Younge B, Goronzy J J
Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Arthritis Rheum. 1997 Jan;40(1):19-26. doi: 10.1002/art.1780400105.
To determine whether clinical heterogeneity in patients with giant cell arteritis (GCA) is correlated with different patterns in the tissue-specific inflammatory response.
Twenty-three patients with typical histomorphologic findings of GCA were grouped according to the presence or absence of jaw claudication and/or visual abnormalities, fever, concomitant polymyalgia rheumatica (PMR), and histologic evidence of giant cell formation. The inflammatory response in temporal artery biopsy specimens was characterized by semiquantification of cytokine messenger RNA (mRNA) transcripts using reverse transcriptase-polymerase chain reaction, followed by oligonucleotide hybridization with cytokine-specific probes. Clinical patterns were then correlated with profiles of tissue cytokines.
Inflammatory cytokines were expressed in all temporal artery tissues. In situ synthesis of interleukin-2 (IL-2), interferon-gamma (IFN gamma), and IL-1 beta mRNA, but not of IL-10 and IL-12 mRNA, distinguished different patterns of inflammation, and these patterns correlated with clinical manifestations of the disease. Patients with evidence of ischemic symptoms, indicated by jaw claudication and/or visual symptoms, typically expressed higher concentrations of IFN gamma mRNA (P = 0.008) and IL-1 beta mRNA (P = 0.02). Presence of fever was correlated with lower copy numbers of IFN gamma (P = 0.02). Formation of giant cells in the granulomatous infiltrates was associated with the local synthesis of IFN gamma mRNA (P = 0.003). Tissue from GCA patients with concomitant PMR contained higher levels of IL-2 mRNA transcripts (P = 0.001).
Variations in the clinical presentation of GCA were correlated with cytokine mRNA expression in the affected temporal arteries. Differences in the effector functions of tissue-infiltrating T cells distinguished disease patterns in which either local ischemic symptoms or systemic involvement was dominant, or in which there was co-occurrence of PMR. Definition of different patterns of inflammation in GCA might, therefore, facilitate the design of differentiated therapeutic approaches.
确定巨细胞动脉炎（GCA）患者的临床异质性是否与组织特异性炎症反应的不同模式相关。
23例具有GCA典型组织形态学表现的患者，根据是否存在颌部跛行和/或视觉异常、发热、合并风湿性多肌痛（PMR）以及巨细胞形成的组织学证据进行分组。颞动脉活检标本中的炎症反应通过逆转录聚合酶链反应对细胞因子信使核糖核酸（mRNA）转录本进行半定量分析，随后用细胞因子特异性探针进行寡核苷酸杂交来表征。然后将临床模式与组织细胞因子谱进行关联。
所有颞动脉组织中均表达炎症细胞因子。白细胞介素-2（IL-2）、干扰素-γ（IFNγ）和IL-1β mRNA的原位合成，而非IL-10和IL-12 mRNA的原位合成，区分了不同的炎症模式，且这些模式与疾病的临床表现相关。有缺血症状证据（以颌部跛行和/或视觉症状为指标）的患者通常表达更高浓度的IFNγ mRNA（P = 0.008）和IL-1β mRNA（P = 0.02）。发热与IFNγ较低的拷贝数相关（P = 0.02）。肉芽肿浸润中巨细胞的形成与IFNγ mRNA的局部合成相关（P = 0.003）。合并PMR的GCA患者的组织中IL-2 mRNA转录本水平较高（P = 0.001）。
GCA临床表现的差异与受累颞动脉中细胞因子mRNA的表达相关。组织浸润性T细胞效应功能的差异区分了以局部缺血症状或全身受累为主，或同时合并PMR的疾病模式。因此，定义GCA不同的炎症模式可能有助于设计差异化的治疗方法。
