老年人巨细胞动脉炎

巨细胞动脉炎,又称颅动脉炎、颞动脉炎或肉芽肿性动脉炎,是颅动脉的疼痛性炎症。50岁以上人群巨细胞动脉炎的年发病率约为3～5/100000。巨细胞动脉炎的显微镜下所见为动脉外膜和中层的炎症性改变:出现淋巴细胞浸润、肉芽组织形成和异物巨细胞,动脉壁出现增厚并继发血栓形成。     

颞动脉炎和风湿性多肌痛症

颞动脉炎(TA)或称巨细胞动脉炎,其与风湿性多肌痛症(PMR)好发于老年人,是白种老年人的常见风湿病。巨细胞动脉炎本应包括 TA 和高安大动脉炎。后者在病理上类似颞动脉炎,但它是一种主要侵犯年轻妇女的大动脉炎。文献中 TA 与巨细胞动脉炎常作为同义词使用,巨细胞动脉炎常即是指 TA。约40～60%TA 患者有风湿性多肌痛症群,而 PMR患者中3～78%颞动脉活检有 TA 病变,78%的阳性率     

巨细胞动脉炎诊治进展

巨细胞动脉炎(GCA)在累及50岁以上老年人的颞动脉时又称巨细胞颞动脉炎(GCTA)。19世纪40年代，在多发大动脉炎中鉴别发现了年轻人GCA(JGCA)。GCA是一种大动脉血管炎，几乎全身血管皆可受累，主要侵犯弹力膜发育良好的大、中动脉，造成类似肉芽肿样炎症和全层动脉炎。     

流式细胞术检测小鼠心脏组织中炎症细胞浸润的方法探讨

目的使用流式细胞技术检测心脏组织损伤后炎性细胞的浸润。方法通过皮下埋置植入式胶囊渗透压缓释泵,分别灌注生理盐水和AngⅡ1000ng/kg/min,制作小鼠高血压模型,7d后取心脏,采用HE染色、WGA和Masson染色观察AngⅡ灌注对心脏重塑的影响;流式细胞术检测心脏组织的炎性细胞浸润的变化。结果与生理盐水灌注组比,AngⅡ灌注明显引起心肌肥大和纤维化,流式细胞检测显示心肌组织中中性粒细胞、T淋巴细胞和巨噬细胞数量明显增加。结论使用流式技术可以定量检测心脏组织的炎性细胞浸润的情况。     

肺功能正常吸烟者和慢性阻塞性肺疾病患者肺腺泡动脉炎症特征

目的 研究肺功能正常吸烟者和慢性阻塞性肺疾病(COPD)患者肺腺泡动脉炎症的病理特点。方法 取手术切除的远离周围型肺癌的正常肺组织,分肺功能正常不吸烟组(A组,10例)、肺功能正常吸烟组(B组,13例)、吸烟COPD稳定期组(C组,10例),比较3组肺腺泡动脉病理结构改变、炎性细胞在非肌型动脉(NMA)、部分肌型动脉(PMA)外膜,肌型动脉(MA)内、中、外膜的浸润水平,并分析其与临床指标的相关性。结果 (1)B组(32.7±7.7)、C组(37.4±4.5)较A组(24.4±5.0)MA比例增高,MA内、中膜增厚,C组MA外膜胶原纤维增生,面积明显增大。(2)B组和C组CD+45白细胞、CD3+总T淋巴细胞、CD8+T淋巴细胞在各型肺腺泡动脉表达的范围和程度均较A组增高,以CD8+T淋巴细胞增高为主,炎性细胞浸润以肺腺泡NMA最为明显,在MA以外膜最显著,且C组较B组明显;而CD4+T淋巴细胞、B淋巴细胞、巨噬细胞、中性粒细胞在3组各型肺腺泡动脉浸润程度比较差异均无统计学意义(P值均＞0.05)。(3)CD45+白细胞、CD3+总T淋巴细胞、CD8+T 淋巴细胞在MA的浸润程度与MA管壁厚度、吸烟指数呈正相关,与第1秒用力呼气容积占预计值百分比呈负相关,CD3+总T淋巴细胞、CD8+T淋巴细胞浸润程度与BODE指数呈正相关,CD8+T淋巴细胞浸润程度与6 min步行距离呈负相关。结论 肺功能正常吸烟者和COPD患者均已出现以CD8+T 淋巴细胞浸润为特征的同性质炎症反应,炎症累及各型肺腺泡动脉,肺动脉炎症是影响COPD临床病程发展的重要因素之一。     

银屑病与免疫分子关系的研究进展

银屑病的组织学特点是明显的炎性细胞浸润和角质细胞增生，浸润的细胞主要是记忆型细胞、中性粒细胞、内衬巨噬细胞及增多的树突状细胞。有证据表明，涉及的免疫机制主要是T淋巴细胞在靶部位的浸润进而产生IFN-γ等介质，诱导表皮细胞增生及活化角质细胞。现将银屑病与免疫分子关系的研究进展综述如下。     

巨细胞性动脉炎

巨细胞性动脉炎又名头部动脉炎、颞动脉炎、肉芽肿性动脉炎及老年人动脉炎。这是一种老年人的疾病,如能早期诊断,用皮质激素治疗,不仅可使症状缓解,且能防止由于动脉阻塞或破裂引起的失明等并发症。流行病学     

颈动脉粥样硬化斑块的形态学及炎性反应与临床表现的观察

目的评价颈动脉粥样硬化斑块形态学变化、炎性反应及其与临床症状的关系。方法选择9例症状性颈动脉粥样硬化性狭窄患者,通过经颅多普勒超声检测,示4例患者有栓子脱落,5例无栓子脱落。对患者均行颈内动脉内膜切除术,取动脉粥样硬化斑块标本,一部分行常规HE染色,观察常规形态学改变;另一部分做免疫组化染色,观察CD3、CD45RO、CD20、α-平滑肌肌动蛋白(α-SMA)及增殖细胞核抗原(PCNA)的表达情况;并观察炎性细胞浸润程度与栓子脱落的关系。结果①光镜下结果显示,在斑块的肩部和纤维帽内可见一些新生小血管、不同程度的炎性细胞浸润及平滑肌细胞减少。炎性细胞主要分布在新生小血管周围,血管增生越明显,浸润的炎性细胞越多,平滑肌细胞减少越明显。②免疫组化染色结果显示,浸润的炎性细胞为CD3和CD45RO染色阳性的T淋巴细胞,主要分布在新生小血管周围;α-SMA在斑块纤维帽内的表达呈不均匀性,部分区域没有表达。PCNA染色呈阳性,证实细胞增殖处于活跃期。③有栓子脱落患者的颈动脉粥样硬化斑块具有更明显的炎性细胞浸润。结论在颈动脉粥样硬化斑块内,以T淋巴细胞为主的炎性反应对斑块的不稳定性起重要作用。     

性传播疾病

一期梅毒皮肤病变组织中浸润的炎性细胞超微结构观察——张晓东等(辽宁第202医院皮肤科110003)；《沈阳部队医药》，2000，13(6)：515—516[为了从形态学角度研究炎性细胞在一期梅毒发病过程中的作用，对其皮损活体组织采用透射电镜技术观察炎性细胞的超微病理变化。结果显示，病变的皮肤组织内普遍可见大量的炎性细胞浸润，在真皮层更为密集。病变早期(硬结期)见大量中性粒细胞、少量巨噬细胞和浆细胞，晚期(溃疡期)巨噬细胞、浆细胞数量增多。中性粒细胞、巨噬细胞胞内有吞入的带有壳膜的梅毒螺旋体及其片段，浆细胞膜表面附有大量的螺旋体。病     

猪囊尾蚴病患者IFN-γ、IL-4的免疫组织化学研究

目的观察猪囊尾蚴病患者局部病灶的病理学特征及IFN-γ/IL-4表达情况,探讨IFN-γ/IL-4在免疫调控中的作用及意义。方法对病变组织进行苏木素伊红(HE)染色观察炎性细胞浸润情况;并用链霉菌抗生物素蛋白—过氧化酶(SP)免疫组织化学方法观察其IFN-γ/IL-4的表达水平。结果45例病变组织中35例有IFN-γ的表达,阳性表达率为77.78%,24例有IL-4的表达,阳性表达率为53.33%,阳性表达多定位于异物巨细胞、淋巴细胞和巨噬细胞的胞浆;脑型囊尾蚴病IL-4的阳性表达强度高于皮肌型。结论猪囊尾蚴感染的病变组织中有多种类型炎细胞浸润,以异物巨细胞、淋巴细胞、嗜酸性粒细胞浸润为主;炎细胞中IFN-γ表达较普遍,同时也有IL-4的表达。     

T cell subsets and expression of immunological activation markers in the arterial walls of patients with giant cell arteritis.

Immunohistochemical features of infiltrating mononuclear cells (MNC) and resident cells were studied in the temporal artery biopsy specimens of 13 patients with histological verified giant cell arteritis (GCA) and in six biopsy specimens from patients with GCA with negative histological findings. Eight temporal artery biopsy specimens from seven patients with unrelated diseases served as controls. In all patients with GCA proved by biopsy an infiltration of T lymphocytes in the arterial wall was observed, most being of the helper/inducer subset. No B lymphocytes, or very few, were seen. Lymphocytes in 10 out of the 13 positive biopsy specimens displayed staining for the class II major histocompatibility complex (MHC) antigen HLA-DR, whereas this was found in only two of eight controls. A minor number of the infiltrating T lymphocytes from seven out of 13 patients with GCA proved by biopsy stained for transferrin receptors, and in six out of the 13 cases they reacted with anti-interleukin 2 receptor antibody. In the arterial wall from all patients with histologically verified GCA we also found an increased number of macrophages, many of them expressing HLA-DR antigens and transferrin receptors. The immunohistochemical pattern of cell phenotypes found in the arterial wall of patients with GCA suggests that the infiltrating T cells are immunologically activated. This finding supports the hypothesis of a predominantly cellular immunological pathogenesis of giant cell arteritis.     

Dendritic cells co-localize with activated CD4+ T cells in giant cell arteritis

OBJECTIVE: Giant cell arteritis (GCA) is a vasculitis predominantly affecting medium- and large-sized arteries. Recent data show the co-localization of dendritic cells and Chlamydia pneumoniae in vascular biopsies from GCA patients. Here we define the topographical relation of dendritic cells and these activated T-cells to determine the antigen presenting cell in GCA, and to examine several auxiliary biochemical and genetic aspects relating to the role of bacteria such as C. pneumoniae in eliciting GCA. METHODS: 18 paraffin-embedded temporal artery biopsy specimens from 14 patients with GCA that were PCR-positive for C. pneumoniae were examined by two-color immunohistochemistry for the topographical relationship between dendritic cells and activated T-cells. In addition the presence of GTP-binding proteins. Tumor necrosis factor alpha (TNF alpha), and Toll-like receptor 4 (TLR4) was investigated. 15 temporal artery specimens from 10 patients without GCA served as controls. RESULTS: In all GCA specimens, dendritic cells co-localized in the immediate vicinity of activated CD4+ Talin-expressing T cells, and these were predominantly found in granulomatous infiltrates. Confocal microscopy confirmed the cell-cell contact of dendritic cells with activated T cells. Results further showed that RhoA and Rac1 were predominantly present in the region of granulomatous infiltrates. TNF alpha production and expression was found in dendritic cells and macrophages, predominantly in granulomatous infiltrates and in endothelial cells of the vasa vasorum dispersed in the adventitial and medial layers of the temporal artery. No control specimens showed TNF alpha expression. More than 95% of dendritic cells were positive for TLR4; macrophages and endothelial cells localized in the adventitia showed TLR4 production. CONCLUSIONS: The immediate co-localization of dendritic cells and activated T cells indicate a high probability that the former represent the antigen presenting cells in GCA. In addition, because of the presence of Rho A and Rac1 in the granulomatous infiltrates, we speculate that they provide the right environment for cell-cell contact and adhesion, and that they may promote the internalization of bacteria. TNF alpha is expressed at high levels in the granulomatous infiltrates of temporal artery specimens from patients with GCA. Since TLR4 is produced in the same cell types, and predominantly in the adventitial layer of the temporal artery, we suggest that these receptors are coupled to signal transduction pathways that control TNF alpha expression.     

Detection of Chlamydia pneumoniae in giant cell vasculitis and correlation with the topographic arrangement of tissue-infiltrating dendritic cells

OBJECTIVE: Recent studies suggest that giant cell arteritis (GCA) may be an antigen-driven disease. Since Chlamydia pneumoniae has been identified in arterial vessel walls, it was hypothesized that this organism might be associated with GCA. METHODS: Fourteen paraffin-embedded temporal artery biopsy specimens from 9 patients with GCA were examined by immunohistochemistry and by polymerase chain reaction (PCR) for the presence of C pneumoniae; for 5 patients, specimens were available from both the left and right arteries. Four temporal artery specimens from 3 patients with polymyalgia rheumatica (PMR) and 9 temporal artery specimens from 5 patients without GCA or PMR served as controls. RESULTS: C pneumoniae was detected by both immunohistochemistry and PCR in 6 GCA patient samples. One GCA patient sample was immunopositive only; another was PCR positive only. Thus, C pneumoniae was found in 8 of 9 GCA patients. One of 4 control samples from the PMR patients was immunopositive, but PCR negative, for C pneumoniae. The C pneumoniae-positive PMR patient also had respiratory symptoms. The remaining 9 control samples were negative for C pneumoniae by both immunohistochemistry and PCR. Immunohistochemistry showed that bacteria predominate in the adventitial layer of temporal arteries, in granulomatous infiltrates. Dendritic cells were examined by immunohistochemistry for their presence and localization in consecutive temporal artery specimens, and showed a strong topographic relationship with C pneumoniae. Like the bacterium, dendritic cells predominate in the adventitial layer of the arteries. CONCLUSION: C pneumoniae was found in temporal artery specimens from most GCA patients, in 1 specimen from a PMR patient, and in no other control specimens; thus, it may play a role in the pathogenesis of the disease. Dendritic cells may represent the antigen-presenting cells in this situation.     

YKL-40 in giant cells and macrophages from patients with giant cell arteritis

OBJECTIVE: YKL-40, a mammalian member of the family 18 glycosyl hydrolases, is secreted by activated macrophages at a late stage of differentiation. Macrophages are present in inflammation of the arterial wall and are thought to participate in the pathogenesis of giant cell arteritis (GCA). The aim of this study was to evaluate whether macrophages and giant cells of patients with GCA produce YKL-40, and whether serum YKL-40 concentrations are elevated in these patients. METHODS: Serum YKL-40 was determined by radioimmunoassay in 19 patients with GCA and 8 patients with polymyalgia rheumatica (PMR) who were followed up prospectively during 1 year of treatment with prednisolone. Immunohistochemical staining for YKL-40 was performed in temporal artery biopsy samples that were obtained before treatment. RESULTS: In the arteritic vessels of patients with GCA, positive staining for the YKL-40 antigen was found in CD68+ giant cells and mononuclear cells located in the media. Macrophages located in the adventitia and intima were negative for YKL-40. At the time of diagnosis, patients with GCA had an increased median serum level of YKL-40 (256 microg/liter; P<0.01) compared with healthy age-matched controls (median 118 microg/liter), and the serum level of YKL-40 decreased to normal levels during prednisolone treatment (-38% after 1 month; P<0.001). Most patients with PMR had normal serum YKL-40 levels (median 158 microg/liter) and had no changes in the serum YKL-40 levels during prednisolone treatment. The observed changes in serum YKL-40 did not always parallel the changes in serum C-reactive protein levels and erythrocyte sedimentation rate during the 1-year study period. CONCLUSION: YKL-40 is found in CD68+ giant cells and mononuclear cells in the media of arteritic vessels of patients with GCA, and the concentration of serum YKL-40 may reflect the local activity of these cells in the inflamed artery.     

Biopsy-negative giant cell arteritis: Does anti-CD83 immunohistochemistry advance the diagnosis?

BACKGROUND: In situ maturation of adventitial dendritic cells (DC) with expression of CD83 has been proposed as an early event in the pathogenesis of giant cell arteritis (GCA), preceding the appearance of an inflammatory infiltrate. The aim of this study was to evaluate the added value of anti-CD83 staining of temporal artery biopsy (TAB) specimens in patients with biopsy-negative temporal arteritis. METHODS: Fourteen patients with TAB performed in our medical center since 2001 and considered negative for GCA due to the absence of any inflammatory infiltrate were identified by a computerized search of patient records. Their paraffin-embedded TAB specimens were retrieved, reprocessed, and stained with anti-CD83 monoclonal antibody (Serotec, 1:40). Three TAB specimens of patients with biopsy-proven GCA served as positive controls and three specimens of popliteal and/or tibial arteries of patients with atherosclerotic peripheral vascular disease were used as negative controls. Follow-up of the patients was confirmed by personal contact with their rheumatologists and analysis of their hospital charts. RESULTS: Follow-up was available for 12 of 14 patients. Five of these patients were considered to have biopsy-negative GCA: they satisfied the ACR classification criteria, were successfully treated with glucocorticosteroids, and had a follow-up of at least 10 months with no alternative diagnosis established. Anti-CD83 staining was negative in all but one patient who demonstrated a single CD83-positive cell adjacent to the internal elastic membrane. Positive anti-CD83 staining of the inflammatory infiltrate throughout the arterial wall was observed in all patients with biopsy-proven GCA (positive controls). Negative controls did not show any CD83-positive cells. CONCLUSIONS: In this pilot study, anti-CD83 immunohistochemical staining of paraffin-embedded specimens did not improve the yield of TAB in patients with suspected GCA.     

Cerebral infarction due to giant cell arteritis-three case reports

The objective of this report was to explore the clinical features of patients with cerebral infarction due to giant cell (temporal) arteritis (GCA) and its characteristic changes in pathology, and on computed tomography (CT) and magnetic resonance imaging (MRI). Three cases of cerebral infarction due to GCA, treated during the past 2 years, were analyzed. Their clinical manifestations were observed carefully, their temporal artery biopsies were performed, their immunohistochemistries were done, and CT as well as MRI were used. The results showed that all the patients had new-onset headache and temporal artery abnormality when the disease began, and there was tremor on the right limbs of 1 patient; temporal artery biopsies revealed evidence of inflammatory cell infiltration in the arterial wall, mainly including T-lymphocytes and macrophages; small cerebral infarction foci were found on CT and MRI; and the responses to corticosteroid therapies were good. The results suggest that it is important to recognize the clinical features of cerebral infarction due to GCA, including the changes of pathology and on CT and MRI. In some cases, special attention is paid to differentiating between atherosclerotic infarction and infections to avoid misdiagnosis.     

Giant cell arteritis in China: a prospective investigation

The objective of this prospective study was to investigate further the clinical features of patients with giant cell (temporal) arteritis (GCA). All patients diagnosed from July 1999 to March 2001 at the Department of Neurology of the Second Xiangya Hospital in China were included. The final diagnosis was based on clinical manifestations, a temporal artery biopsy, response to steroid, and follow-up. The American College of Rheumatology (ACR) criteria for the classification of GCA were tested in the patients identified. Sixteen patients with GCA were identified; 13 (81.25%) patients fulfilled the 1990 ACR criteria for the classification of GCA. Clinical findings included the following: mean age at disease onset 43.13 years (range 28-60) and 81.25% of the patients under the age of 50 when the disease began; men 93.75%; the common initial symptoms including new headache 62.50% and.visual symptoms 18.75%; the common clinical findings at presentation including new headache 93.75%, temporal artery abnormality 81.25%, visual abnormality 56.25%, and fever 25.00%; raised erythrocyte sedimentation rate (ESR) 68.75%; and uncommon findings including jaw claudication, ptosis, fatigue, syncope, hemiparesis; all 16 patients underwent a temporal artery biopsy; inflammatory cell infiltration 68.75% in arterial wall, fragmented internal elastica 100.00%, fibrinoid necrosis 18.75%, smooth muscle cell changes 62.50%, and thrombosis in the lumen 31.25%. The mean time from symptom onset to suspicion of GCA or biopsy was 5.52 months (range 0.25-24.33); the initial diagnosis was wrong in 87.50% of patients. These examples are too small a number to permit definite conclusion. But the results suggest that GCA may not be a rare disorder in China, mean age at disease onset was relatively young, males may be more susceptible, the clinical features of GCA have not been widely appreciated yet, there was a delay between diagnosis and treatment, and initial diagnosis was wrong in many patients.     

Expression of interleukin‐32 in the inflamed arteries of patients with giant cell arteritis

Objective

Giant cell (temporal) arteritis (GCA) is a vasculitis that mainly affects the large and medium arteries, especially the branches of the proximal aorta. Interleukin‐32 (IL‐32) is a recently described Th1 proinflammatory cytokine, and is mainly induced by interferon‐γ (IFNγ), IL‐1β, and tumor necrosis factor α (TNFα). This study was undertaken to investigate the expression and tissue distribution of IL‐32 in artery biopsy specimens from patients with GCA.

Methods

Quantitative gene expression analysis of IL‐32, IL‐1β, TNFα, IFNγ, IL‐6, and IL‐27 was performed in artery biopsy specimens obtained from 18 patients with GCA and 15 controls. Immunohistochemistry analysis was performed to evaluate IL‐32 tissue distribution and identify IL‐32–producing cells. Circulating Th1 lymphocytes were evaluated by flow cytometry.

Results

We demonstrated a strong and significant up‐regulation of IL‐32 at both the messenger RNA and protein levels in the artery biopsy samples from patients with GCA. IL‐32 was abundantly expressed by vascular smooth muscle cells of inflamed arteries and neovessels within inflammatory infiltrates. IL‐32 expression strongly correlated with the intensity of the systemic inflammatory response. IL‐32 overexpression was accompanied by strong overexpression of Th1 cytokines, such as IFNγ and IL‐27p28, in inflamed arteries from GCA patients. The Th1 lymphocyte population was also expanded among peripheral blood mononuclear cells from GCA patients and produced higher amounts of IL‐32 compared to controls.

Conclusion

Our findings indicate that overexpression of IL‐32 together with a clear Th1 response immunologically characterizes the inflammatory response in GCA. In particular, IL‐32 seems to be an important mediator of artery inflammation in GCA.

     

Tissue-destructive macrophages in giant cell arteritis.

Giant cell arteritis (GCA) is an inflammatory vasculopathy in which T cells and macrophages infiltrate the wall of medium and large arteries. Clinical consequences such as blindness and stroke are related to arterial occlusion. Formation of aortic aneurysms may result from necrosis of smooth muscle cells and fragmentation of elastic membranes. The molecular mechanisms of arterial wall injury in GCA are not understood. To identify mechanisms of arterial damage, gene expression in inflamed and unaffected temporal artery specimens was compared by differential display polymerase chain reaction. Genes differentially expressed in arterial lesions included 3 products encoded by the mitochondrial genome. Immunohistochemistry with antibodies specific for a 65-kDa mitochondrial antigen revealed that increased expression of mitochondrial products was characteristic of multinucleated giant cells and of CD68+ macrophages that cluster in the media and at the media-intima junction. 4-Hydroxy-2-nonenal adducts, products of lipid peroxidation, were detected on smooth muscle cells and on tissue infiltrating cells, in close proximity to multinucleated giant cells and CD68+ macrophages. Also, giant cells and macrophages with overexpression of mitochondrial products were able to synthesize metalloproteinase-2. Our data suggest that in the vascular lesions characteristic for GCA, a subset of macrophages has the potential to support several pathways of arterial injury, including the release of reactive oxygen species and the production of metalloproteinase-2. This macrophage subset is topographically defined and is also identified by overexpression of mitochondrial genes. Because these macrophages have a high potential to promote several mechanisms of arterial wall damage, they should be therapeutically targeted to prevent blood vessel destruction.     

Giant cell arteritis presenting as limb claudication. Report and review of the literature.

Upper limb claudication and pulselessness is an uncommon presentation of giant cell arteritis (GCA), often resulting in delayed diagnosis. We describe such a case diagnosed by angiography, in which a temporal artery biopsy showed classic GCA, despite the absence of local signs or symptoms. A review of 26 similar cases revealed that in 81% of patients where the only manifestation of GCA was upper limb findings, temporal artery biopsy yielded positive findings. Steroid therapy clinically improved 24/26 patients. These findings suggest that a consideration of temporal artery biopsy early in the investigation will hasten diagnosis and appropriate therapy.