S S Uppal1, S Verma. 1. Department of Medicine, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait. uppalss@hsc.kuniv.edu.kw
Abstract
OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.