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Background: The role of soluble ST2, the IL-33 receptor, in the pathogenesis of rheumatoid arthritis (RA) is discussed in the literature.
Objectives: to assess the levels of soluble ST2 marker initially (against the background of ineffective basic anti-inflammatory therapy (DMARD) and after 12 months of combination therapy (DMARD + biological therapy).
Methods: The study included 47pts (39 women /8 men) with RA, 51 [39,0; 63,0] years old. Pts were seropositive for IgM RF (79%) and anti-CCP (62%), with highly active RA (DAS28 5,7 [5,2; 6,4]; SDAI 35,0 [29,1; 43,6], CDAI 34,0 [25,0; 43,0]) scores, and median disease duration of 4.0 [3,0;14.0] years. All patients with RA had a history of insufficient effect or intolerance to two or more basic anti-inflammatory drugs (DMARDs). At the time of inclusion in the study, patients received DMARDs: 44% of patients received methotrexate (median dose - 15 (15; 20) mg /week), 35% - leflunomide (20 mg / day), 9.3 % - sulfasalazine (2000 mg / day), 7% - hydroxychloroquine (200 mg / day), 67.4% - glucocorticoids (5 (4; 8) mg / day). Patients did not receive biological therapy at the time of inclusion in the study. Due to lack of efficacy or intolerance, patients with RA (n=21) were prescribed biological therapy: 52.4% - anti-B-cell therapy, 38% - TNF-alpha inhibitors, 9.6% - IL-6 inhibitors. The control group consisted of 20 age-matched donors without rheumatic diseases. The concentration of soluble ST-2 was determined by enzyme immunoassay (Cristal Diagnostics, San Diego). The upper limit of normal when testing 20 sera from healthy donors was 17,65 ng/ml, corresponding to the 95th percentile.
Results: The serum level of soluble ST2 in patients with late RA (n=47) was higher than in the control group (n=20) (14.2 [11.5;20.1] ng/ml versus 10.65 [9.3; 13.1 ng/ml) (p<0.001). Patients with RA and elevated serum ST2 levels (≥17.65 ng/mL) were older than patients with ST2 levels ≤17.65 ng/mL (58.5 [50;68] vs 47, 0 [38;59] years) (p=0.007). In the group of patients (n=21) who received combination therapy for 12 months, there was a statistically significant decrease in clinical and laboratory activity, levels of RF IgM and soluble ST2 in blood serum, compared with baseline (13.8 [11.5; 18.4] ng/ml vs 12.5 [9.6;13.8] ng/ml (p<0.05 in all cases).(
| Patients with RA (n=21) with insufficient effect of basic anti-inflammatory therapy | Patients with RA (n=21) after 12 months of receiving combination therapy | Δ,% | р | |
|---|---|---|---|---|
| BMI, kg/m 2 | 24,16 (21,23; 26) | 25,15 (23,43;26,7) | +4,1 | 0,8 |
| DAS28 | 5,6 (5,3; 6,7) | 3,97(3,36;4,63)* | -30,4 | 0,0001 |
| SDAI | 38,17 (29,5; 45,8) | 17,2(9,57;25,6)* | -54,8 | 0,0001 |
| CDAI | 35,0 (26,0; 43,5) | 17,0(9,0;23,5)* | -51,4 | 0,0001 |
| СRP,mg/l | 20,6 (11,7;34,1) | 3,15(1,2;7,2)* | -84,7 | 0,003 |
| ESR,mm/h | 27,0 (16,0;45,0) | 16,0 (10,0;23,5)* | -40,7 | 0,003 |
| IgM RF, МЕ/ml | 84,4 (20,8;163,0) | 32,2(10,6;107)* | -61,8 | 0,01 |
| ST-2, ng/ml | 13,8 (11,5;18,4) | 12,5(9,6;13,8)* | -9,4 | 0,008 |
* -p <0.05 reliability of differences in indicators before and after 12 months of combination therapy (Wilcoxon); Δ,% - the difference in indicators between the groups by the 12th month of combination therapy.
Conclusion: In patients with high RA activity and the ineffectiveness of basic anti-inflammatory therapy, the level of soluble ST2 in serum was increased compared to the control group. After 12 months of effective anti-rheumatic therapy, the level of this marker decreased. The association of this marker with the clinical and laboratory activity of RA suggests its role in the development of rheumatoid inflammation.
Disclosure of Interests: None declared