Background/Purpose:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

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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/