Background Recent treatment of rheumatoid arthritis (RA) was dramatically improved after introducing biological agents. Although there are limited number of reports that analyzed the effect of biological agents from the view point of histopathology, the specific findings and the significance of biological agents on histological changes of joint synovium is remained uncertain.
Objectives The purpose of this study was to compare the histopathological findings of synovium in patients with RA between 2 groups with and without use of the biological agents.
Methods 79 biopsy specimens of synovium were obtained during joint surgery from 67 cases of RA. The histopathological findings of synovium in each specimen were evaluated and scored for detailed findings such as synoviocyte hyperplasia, fibrosis, proliferating blood vessels, perivascular infiltrates of lymphocytes, focal aggregates of lymphocytes, and diffuse infiltrates of lymphocytes using the histological score of the synovium by Rooney et al. For immunohistochemistry, tissue sections were stained with TNF-a mouse monoclonal antibody and IL-6 rabbit polyclonal antibody. Then each microscope slides was assessed and compared between two groups. Group with the use of biological agents (Group A) included 30 cases with 39 joint specimens. In Group A, 12 cases (15 joints) used etanercept, 12 cases (15 joints) used infliximab, 3 cases (4 joints) used tocilizumab, and 3 cases (5 joints) used adalimumab at the time of surgery. Group without use of biological agents (Group B) included 37 cases with 37 joints. These cases underwent surgery during same study period as Group A. The variations of surgery in both group was similar. The background data such as age, averaged duration of disease, CRP, MMP-3, DAS-28 score, and mean dose of methotrexate (MTX) and prednisolone (PSL) were not different between two groups.
Results Group A showed significantly decreased scores in synovial hyperplasia, perivascular infiltrates of lymphocytes, focal aggregates of lymphocytes, diffuse infiltrates of lymphocytes and also total score than in the Group B. In contrast, Group A showed significantly increased scores in fibrosis. No correlation between total Rooney’s score and age, Larsen’s classification, Steinblocker’s classification, duration of disease, or preoperative values of CRP and MMP-3 was found in each group. In Group A, no difference of total Rooney’s score was found by variety of biologics, additionally, there was no correlation between total Rooney’s score and the duration of administration of biologics. Although no correlation was found between mean dose of MTX and total Rooney’s score in each group, Group A showed negative correlation between dose of PSL and total Rooney’s score (p=0.015). The results of immunohistochemistry showed that Group A had significantly less cases stained with TNF-a than in Group B (p<0.01). For IL-6 stain, no difference was observed between two groups.
Conclusions Based on these results, fibrosis around the synovium was thought to be one of specific findings of the effect of biological agents for RA. The negative correlation between dose of PSL and total Rooney’s score in Group A may suggest some synergistic effect of PSL and biologics.
Disclosure of Interest None Declared
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