A Pusztai

A4.3 Effects of anti-TNF therapy on markers of bone homeostasis in rheumatoid arthritis and ankylosing spondylitis

Background and objectives Uncoupling of bone resorption and formation has been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Generalised bone loss and erosions are characteristic for RA, while in AS, bone formation overrides resorption. The RANKL/OPG and the Wnt/DKK-1/sclerostin systems have been implicated in disturben bone homeostasis in arthritides. Anti-TNF biologics may beneficially influence erosions and bone loss in RA, however, they have little effect on bone formation in AS. In the present study, we assessed the effects of 1-year anti-TNF treatment on various bone biomarkers. Patients and methods Altogether 43 arthritis patients including 30 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 13 AS patients treated with ETN were included in a 12-month follow-up study. Disease activity (DAS28 or BASDAI), CRP, IgM rheumatoid factor, anti-CCP, calcium (Ca), phosphate (P), osteocalcin (OC), P1NP, CTX, BNP, sclerostin (SOST), DKK-1, soluble RANKL (sRANKL), cathepsin K (cathK) and vitamin D3 (vitD) levels were assessed at baseline, as well as 6 and 12 months after treatment initiation. Results Anti-TNF treatment was highly effective in both diseases, as the mean DAS28 decreased from 6.32 to 3.16 (p = 0.02) in RA, mean BASDAI decreased from 5.87 to 1.84 (p < 0.001) in AS. In RA, anti-TNF treatment significantly decreased DKK-1 (60.5 ± 28.9 pM and 54.7 ± 20.8 pM, p = 0.036) and CathK (28.7 ± 6.2 pm and 26.8 ± 4.0 pm, p = 0.014) but increased SOST (107.0 ± 47.5 pM and 131.2 ± 85.2 pM, p = 0.04) levels from baseline to 12 months, respectively. In RA, ETN and CZP treatment also increased OPG/sRANKL ratio after 6 months (51.9) vs. baseline (43.9) (p = 0.01). In AS, ETN therapy significantly increased the bone formation marker P1NP (49.4 ± 19.0 pM and 56.9 ± 28.7 pM, p = 0.03) and SOST (70.6 ± 29.0 pM and 82.4 ± 48.3 pM, p = 0.022) levels from baseline to 12 months, respectively. ETN therapy also increased OPG/sRANKL ratio after 6 months (44.5) and 12 months (46.9) compared to baseline (34.5) in AS (p < 0.01). Both baseline and 12-month SOST levels were significantly lower in AS compared to RA (p < 0.001). When RA and AS data were pooled, TNF inhibition resulted in significantly decreased DKK-1 (p = 0.035) and cathK (p = 0.008) but increased P1NP (p = 0.04) and SOST (p = 0.04) after 12 months. In this study, biologics did not affect Ca, P, OC, CTX, BNP, vitD levels. Conclusions In a mixed cohort of RA and AS patients, anti-TNF therapy resulted in a restoration of bone homeostasis by decreasing DKK-1 and CathK, increasing P1NP, SOST and OPG/sRANKL ratio. Lower SOST levels in AS compared to RA, as well as the induction of bone formation over resorption may account for the inefficacy of TNF inhibitors on syndesmophyte formation in AS.

Rheumatoid arthritises biobankkal szerzett tapasztalataink: 204 beteg biológiai mintáinak és klinikai adatainak összevetése

Absztrakt: Bevezetes: A biobank a betegektől szarmazo biologiai mintak mellett a genetikai elteresek, klinikai adatok rogzitesere is alkalmas. Szamos biobankot hoztak letre vilagszerte, amelyek jelentősen hozzajarultak a betegsegek es genetikai polimorfizmusok szerepenek jobb megismeresehez, illetve a kulonboző korkepek kezelesi hatekonysaganak novelesehez. Celkitűzes: A munka soran az volt a celunk, hogy letrehozzunk egy internetes biobankot, amelyben rheumatoid arthritises betegekre vonatkozo laborparameterek, genetikai jellegzetessegek, tarsbetegsegek rendszerezese megoldhato, megkonnyitve a kutatomunkat, a betegseg jobb megismereset, illetve megakadalyozva az adatvesztest. Betegek es modszer: Osszesen 204 rheumatoid arthritises beteg eseteben rendelkezunk biologiai mintakkal, es a 204 beteg adatait sikerult a biobankban rogziteni, amely a http://rheuma.biobank.eu honlapon talalhato. Az adatok felhasznalasaval az SPSS20 program segitsegevel elvegeztuk a leiro statisztikai vizsgalatokat es a korrelaciok...INTRODUCTION A biobank is a registry, which is suitable for the storage of biological samples (e.g. tissues, DNA, protein), genetical abnormalities and clinical data. Several biobanks have been created worldwide, which contribute to research and the better understanding of disease pathogenesis, genetical polymorphisms. Biobanking also helps to improve the efficacy of therapies. AIM Our purpose was to create an internet-based biobank, in which laboratory test results, genetic alterations and related disorders of rheumatoid arthritis (RA) patients can be registered. This biobank would be able to make the research easier and it can help to improve our knowledge about diseases and it can inhibit loss of data. PATIENTS AND METHOD We have biological samples from 204 RA patients and we have entered their data in the biobank which can be found on the website http://rheuma.biobank.eu . Statistical analysis was performed by SPSS20 statistical programme. RESULTS By the creation of biobank that contains clinical data and biological samples of 204 RA patients, we have a database which can help to improve our knowledge about the disease and help to develop new treatment strategies. CONCLUSION Biobanking is suitable to analyze blood samples and clinical data together. Orv. Hetil., 2017, 158(7), 270-277.

AB0042 Natural Autoantibodies Against Citrate Synthase and DNA Topoisomerase I in Patients with Rheumatoid Arthritis and Spondyloarthritis Receiving Anti-TNF-α Therapy

Background and objectives Natural autoantibodies bind to evolutionarily conserved antigens in organs and tissues of the body and may have regulatory functions in the immune system and play a role in the clearance of apoptotic cells. It has been known that some patients treated with anti-TNF-α agents develop autoantibodies, including antinuclear and anti-double-stranded DNA antibodies. However, in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) treated with TNF-α blockers there have been no studies regarding the presence of natural autoantibodies against citrate synthase (CS), a mitochondrial inner membrane enzyme, and DNA topoisomerase I (topo I), an enzyme that relaxes the superhelical stress in DNA. Therefore, our aim was: (1) to investigate whether patients with RA and SpA receiving anti-TNF-α treatment produce natural autoantibodies to CS and topo I; and (2) to test whether such therapy affects the levels of these autoantibodies. Materials and methods The study included a total of 36 patients (20 with RA, 16 with SpA) who received certolizumab or etanercept therapy. The levels of anti-CS and anti-topo I (immunodominant fragment) autoantibodies (IgM and IgG) were measured in the blood serum using enzyme-linked immunosorbent assay developed in our laboratory. The measurements were done at the starting point (0), 6, or 12 months of therapy. Results In the combined patient group (RA + SpA) we detected significantly increased levels of anti-CS IgM and IgG antibodies after 6 and 12 months of anti-TNF-α therapy. The anti-topo I IgM and IgG were significantly elevated only after 12 months of therapy, when compared to baseline antibody levels before the start of treatment. Conclusions The significance of the presence of anti-CS and anti-topo I natural autoantibodies is still a subject of research. We hypothesise that the increase in the levels of these natural autoantibodies might be a marker for the functional role of the natural immune system in patients treated with anti-TNF-α blockers. Because TNF-α is a pleiotropic cytokine, blocking its function can elicit various side-effects, including haematological, immunological, and others. Natural autoantibodies may function in the clearance of apoptotic cells and they may help restore the immunological milieu by reducing inflammation and protecting against some infections, functions in which the natural immune system has been implicated.

AB0082 Effects of Anti-Tnf Therapy on Circulating Oxldl-Beta2Gpi Complex Levels in Arthritis

Background and objectives Accelerated atherosclerosis, increased cardiovascular (CV) morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Oxidised LDL (oxLDL) and beta 2 glycoprotein I (beta2gpI) antigens have been implicated in atherosclerosis, as well as antiphospholipid syndrome. High circulating oxLDL/beta2gpI levels may reflect vascular damage in acute coronary, syndrome, SLE, and other autoimmune diseases. However, the role of these complexes in RA and AS has not yet been evaluated in relation to therapy. Therefore, circulating complex levels, as well as the effects of anti-TNF therapy on these complexes were assessed in RA and AS patients. Complex levels were also correlated with various autoimmune-innflammatory and metabolic markers. Patients and methods Altogether 43 arthritis patients including 30 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 13 AS patients treated with ETN were included in a 12-month follow-up study. Circulating oxLDL/beta2gpI complexes were assessed by an AtherOx® ELISA system (Corgenix). In addition, disease activity (DAS28 or BASDAI), CRP, IgM rheumatoid factor, anti-CCP, and lipid levels (total cholesterol, TC; LDL-C, HDL-C and triglyceride) were also assessed. Assessments were performed at baseline, as well as 6 and 12 months after treatment initiation. Results Anti-TNF treatment was highly effective in both diseases, as the mean DAS28 decreased from 6.32 to 3.16 (p = 0.02) in RA, mean BASDAI decreased from 5.87 to 1.84 (p < 0.001) in AS. In RA, AS and the mixed arthritis population (n = 43) baseline oxLDL/beta2gpI levels were 0.235 ± 0.1, 0.245 ± 0.1 and 0.238 ± 0.1, respectively. There were no significant differences between RA and AS patients. In RA, ETN/CZP treatment resulted in non-significant decreases in complex levels after 6 months (0.214 ± 0.1) and 12 months (0.206 ± 0.1). In AS, oxLDL/beta2gpI complex levels did not change after 6 months of ETN therapy, but significantly decreased after one year (0.195 ± 0.1; p = 0.01). In the RA+AS population, anti-TNF treatment significantly decreased oxLDL/beta2gpI levelés after 12 months (0.203 ± 0.1, p = 0.02). In addition, baseline oxLDL/beta2gpI complex levels positively correlated with TC (RA: r = 0.563, p = 0.002; AS: r = 0.542, p = 0.049; RA+AS: r = 0.532, p < 0.001), and LDL-C (RA: r = 0.630, p < 0.001; AS: r = 0.756, p = 0.004; RA+AS: r = 0.648, p < 0.001) in both diseases. Circulating oxLDL/beta2gpI levels did not correlate with DAS28, BASDAI or CRP. Conclusions In a mixed cohort of RA and AS patients, anti-TNF therapy suppressed the circulating levels of oxLDL/beta2gpI complexes, markers of atherosclerosis and vascular disease in SLE or APS. Moreover, oxLDL/beta2gpI levels correlated with TC and LDL-C in arthritides. oxLDL/beta2gpI complexes do not seem to be markers of disease activity in RA or AS.