Uppal S S, Verma S
Department of Medicine, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait.
Clin Exp Rheumatol. 2003 Nov-Dec;21(6 Suppl 32):S112-6.
To evaluate clinical and immunological abnormalities in patients with Takayasu's arteritis (TA) from India, with particular reference to autoimmune perturbations and abnormalities in T cell subsets (CD4 and CD8 cells).
16 consecutive patients with TA (11 females and 5 males) underwent clinical and laboratory evaluation inclusive of flow cytometric analysis of T cell subsets (CD4 and CD8). A control population of 94 age- and sex-matched blood donors was used to determine the normal T cell subsets. Student's t-test was used to compare the means.
The mean age at onset was 23.4 + 2.3 yrs. Common symptoms observed were headache, limb claudication, abdominal pain and visual disturbance/blackout. Common clinical signs observed included reduced arterial pulsations, bruits, and a BP difference > 10 mm Hg in the upper limbs. Systemic hypertension was documented in 12 patients. The mean absolute lymphocyte count in the patients was 2289/mm3. The mean CD4 count and CD4% were 1003 and 41 respectively; the mean CD8 count and CD8% were 755 and 34, respectively; and the mean CD4/8 ratio was 1.41. The patients had statistically significantly higher CD8 but not CD4 T cell values than controls. IgG and IgM immunoglobulin levels were increased. The mean multi-test CMI score in patients using CMI multi-test device of Pasteur Merieux was 14.6 mm. Two patients had an anergic response, 4 a partial response (1-13 mm), and 6 a full response of > 13 mm. Four patients hyper-responded with a score of > 20 mm. ANCA was positive in 2 patients. ANA was positive in 3 patients. IgG anticardiolipin was positive in 12 patients and IgM in 3; overall 12 patients were anticardiolipin positive by ELISA. Anti-beta 2GPI of the IgG variety was found to be positive in 3 patients and IgM in 2 patients; overall 3 patients being positive for the same. Nine of the patients with active disease were started on a combination of moderate dose prednisolone (20-40 mg once daily) along with weekly oral methotrexate (7.5-15.0 mg). Surgical intervention was required in 6 patients.
This study found an increase in CD8 positive T cell subsets, increased IgG and IgM immunoglobulin levels, and the presence of autoantibodies including ANA, ANCA, anticardiolipin and anti-beta 2GPI antibodies in TA patients. TA may be an autoimmune disorder with T cell aberrations. The relationship with antiphospholipid antibodies and anti-beta 2GPI needs to be explored and confirmed by other larger studies. The strikingly positive responses to tuberculin, as well as the multi-test CMI also indicate exaggerated T cell responses and cell mediated immunity in Takayasu's arteritis. Immunosuppressive therapy was successful in controlling disease activity in the majority, but surgery was needed for irreversible stenotic lesions.
评估来自印度的大动脉炎（TA）患者的临床和免疫异常情况，特别关注自身免疫紊乱及T细胞亚群（CD4和CD8细胞）异常。
16例连续的TA患者（11例女性，5例男性）接受了临床和实验室评估，包括T细胞亚群（CD4和CD8）的流式细胞术分析。选取94名年龄和性别匹配的献血者作为对照人群，以确定正常的T细胞亚群。采用学生t检验比较均值。
发病的平均年龄为23.4±2.3岁。观察到的常见症状有头痛、肢体间歇性跛行、腹痛及视力障碍/黑矇。观察到的常见临床体征包括动脉搏动减弱、血管杂音以及上肢血压差>10 mmHg。12例患者记录有系统性高血压。患者的平均绝对淋巴细胞计数为2289/mm³。平均CD4计数和CD4%分别为1003和41；平均CD8计数和CD8%分别为755和34；平均CD4/8比值为1.41。与对照组相比，患者的CD8 T细胞值在统计学上显著升高，但CD4未升高。IgG和IgM免疫球蛋白水平升高。使用巴斯德梅里埃CMI多检测设备的患者平均多检测CMI评分为14.6 mm。2例患者有无反应，4例部分反应（1 - 13 mm），6例完全反应>13 mm。4例患者超反应，评分>20 mm。2例患者ANCA阳性。3例患者ANA阳性。12例患者IgG抗心磷脂阳性，3例患者IgM抗心磷脂阳性；总体而言，12例患者通过ELISA检测抗心磷脂阳性。发现3例患者IgG型抗β₂糖蛋白Ⅰ阳性，2例患者IgM型抗β₂糖蛋白Ⅰ阳性；总体3例患者此项阳性。9例活动期疾病患者开始接受中等剂量泼尼松龙（每日一次20 - 40 mg）联合每周口服甲氨蝶呤（7.5 - 15.0 mg）治疗。6例患者需要手术干预。
本研究发现TA患者中CD8阳性T细胞亚群增加、IgG和IgM免疫球蛋白水平升高，且存在包括ANA、ANCA、抗心磷脂和抗β₂糖蛋白Ⅰ抗体在内的自身抗体。TA可能是一种伴有T细胞异常的自身免疫性疾病。抗磷脂抗体和抗β₂糖蛋白Ⅰ的关系需要通过其他更大规模的研究进行探索和证实。对结核菌素以及多检测CMI的显著阳性反应也表明大动脉炎中T细胞反应和细胞介导免疫增强。免疫抑制疗法在大多数情况下成功控制了疾病活动，但对于不可逆的狭窄病变需要手术治疗。
