PMID- 32392807 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2077-0383 (Print) IS - 2077-0383 (Electronic) IS - 2077-0383 (Linking) VI - 9 IP - 5 DP - 2020 May 7 TI - Aggrecan Turnover in Women with Rheumatoid Arthritis Treated with TNF-alpha Inhibitors. LID - 10.3390/jcm9051377 [doi] LID - 1377 AB - This study was performed to evaluate the effects of 15-month anti-tumor necrosis factor alpha (anti-TNF-alpha) therapy on the aggrecan turnover of female rheumatoid arthritis (RA) patients. Serum was obtained from healthy subjects and female RA patients treated with TNF-alpha inhibitors (TNFalphaI) in combination with methotrexate. We measured serum levels of aggrecan chondroitin sulfate 846 epitope (CS846), aggrecan fragments (AGC), disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and 5 (ADAMTS-5), as well as their natural inhibitor, known as tissue inhibitor of matrix metalloproteinase-3 (TIMP-3), using immunoassay methods. Serum levels of CS846, AGC, ADAMTS-4, ADAMTS-5 and TIMP-3 were higher in female patients with RA before the treatment in comparison to healthy subjects. Ratio of ADAMTS-5 to TIMP-3 was significantly higher in RA women than in controls, whereas ADAMTS-4/TIMP-3 ratio did not differ from that in controls. During the anti-TNF-alpha therapy, the serum levels of 846 epitope increased, whereas levels of AGC decreased in female RA patients. Furthermore, 15 months of treatment with TNFalphaI downregulated serum levels of both ADAMTS, without any effect on TIMP-3 levels. These changes were accompanied by significantly reduced ratios of ADAMTS to TIMP-3. According to our results, anti-TNF-alpha therapy has a beneficial impact on aggrecan remodeling during RA. FAU - Szeremeta, Anna AU - Szeremeta A AD - Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, 41-200 Sosnowiec, Poland. FAU - Jura-Poltorak, Agnieszka AU - Jura-Poltorak A AD - Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, 41-200 Sosnowiec, Poland. FAU - Zon-Giebel, Aleksandra AU - Zon-Giebel A AD - Silesian Center of Rheumatology, Rehabilitation and Prevention of Disability of Gen. Jerzy Zietek in Ustron, 43-450 Ustron, Poland. FAU - Kopec-Medrek, Magdalena AU - Kopec-Medrek M AD - Department of Internal Medicine and Rheumatology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, 40-635 Katowice, Poland. FAU - Kucharz, Eugeniusz Jozef AU - Kucharz EJ AD - Department of Internal Medicine and Rheumatology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, 40-635 Katowice, Poland. FAU - Olczyk, Krystyna AU - Olczyk K AD - Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, 41-200 Sosnowiec, Poland. LA - eng GR - 2013/09/N/NZ5/00815/National Science Centre, Poland/ GR - KNW-2-O21/N/8/N/Medical University of Silesia, Katowice, Poland/ PT - Journal Article DEP - 20200507 PL - Switzerland TA - J Clin Med JT - Journal of clinical medicine JID - 101606588 PMC - PMC7290997 OTO - NOTNLM OT - ADAMTS OT - AGC OT - CS846 OT - TIMP-3 OT - aggrecan OT - rheumatoid arthritis OT - tumor necrosis factor-alpha inhibitors COIS- The authors declare that there are no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2020/05/13 06:00 MHDA- 2020/05/13 06:01 PMCR- 2020/05/07 CRDT- 2020/05/13 06:00 PHST- 2020/03/25 00:00 [received] PHST- 2020/04/20 00:00 [revised] PHST- 2020/05/01 00:00 [accepted] PHST- 2020/05/13 06:00 [entrez] PHST- 2020/05/13 06:00 [pubmed] PHST- 2020/05/13 06:01 [medline] PHST- 2020/05/07 00:00 [pmc-release] AID - jcm9051377 [pii] AID - jcm-09-01377 [pii] AID - 10.3390/jcm9051377 [doi] PST - epublish SO - J Clin Med. 2020 May 7;9(5):1377. doi: 10.3390/jcm9051377.