Session Type: Abstract Submissions (ACR)
The recently established scoring system of American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) early arthritis diagnosis criteria have assigned scores of 0, 1, and 2, respectively, for negative, positive (low titer), and positive (high titer) results of anti-cyclic citrullinated protein (anti-CCP) antibody tests. Thus, high anti-CCP antibody titer is unfavorable in the pathological condition of rheumatoid arthritis (RA). We investigated the changes of anti-CCP antibody and immunoglobulin titers after treatment using tocilizumab (TCZ), which is the biological product of an interleukin (IL)-6 inhibitor agent.
Subjects were 40 RA patients (6 men, 34 women). The patient backgrounds were as follows: age, 25–76 years; mean age, 58.1 ± 11.8 years; mean disease duration, 8.8 ± 8.4 years (range, 1–45 years). TCZ 8 mg/kg was intravenously administered every 4 weeks and was continued for 52 weeks. Evaluations were performed at 3 time points: at the start of the treatment, after 12 weeks, and after 52 weeks. The methods of evaluations were as follows: after calculation of the patient’s disease activity score (DAS28), quantitative determination of serum C-reactive protein (CRP) and immunoglobulin levels was performed by TIA. Anti-CCP antibody was measured using CL-JACK with a designated reagent and an anti-CCP test kit. IL-6 was evaluated using CLEIA. In addition, lymphocyte phenotypes were analyzed for CD3/CD19, CD4/CD25, and CD8/CD11 levels with the corresponding antibodies by using a flow cytometer.
Of the 40 RA patients, 34 patients showed effective improvement in the DAS28; further, although effective, 6 patients showed insufficient DAS28. All CRP values of effective cases after the 12-week evaluation were less than the cut-off value (0.02 μg/ml). Comparison of the immunoglobulin levels at the start of the treatment and after 52 weeks of treatment were respectively as follows: IgG, 1550.1 ± 518.9 mg/ml and 1162.2 ± 431.9 mg/ml, p < 0.0006; IgA, 287.9 ± 112.2 mg/ml and 234.7 ± 89.9 mg/ml, p < 0.002; IgM, 119.9 ± 68.0 mg/ml and 111.9 ± 59.1 mg/ml, not significant (NS). A significant decrease was observed in IgG and IgA levels. No changes were observed in the CD3 (68.2 ± 11.7% and 65.2 ± 11.2%; NS), CD19 (12.5 ± 8.1 and 14.3 ± 8.7%; NS), and number of lymphocytes. The results at the beginning and after 52 weeks of treatment for anti-CCP antibody were 207.0 ± 281.2 U/ml and 253.6 ± 336.4 U/ml (NS) and IL-6, 22.7 ± 35.6 pg/ml and 31.8 ± 40.1 pg/ml (NS). No statistically significant differences were observed.
It can be confirmed from our study results that administration of TCZ decreases immunoglobulin levels in all patients. This result is understood clearly by blocking the differentiation-inducing effect from B-cell lymphocytes to plasma cells, which originally is an action of IL-6. Despite the possibility that a decrease in the levels of anti-CCP antibodies can be misinterpreted, no such observations were noted. A suppressive action on B-cell differentiation is assumed because of the changes in lymphocytes (CD19+) in the patient blood samples. However, TCZ is considered to have no suppressive action on anti-CCP antibody production at the local inflammation sites in RA patients.
« Back to 2012 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/changes-in-the-levels-of-anti-cyclic-citrullinated-protein-antibody-and-immunoglobulins-in-rheumatoid-arthritis-patients-after-administration-of-tocilizumab/