de Reus, Nikki (2021) Het effect van rituximab op de samenstelling van speeksel bij het syndroom van Sjögren. thesis, Dentistry.
Full text available on request.Abstract
Introduction Clinical studies on the effect of rituximab, a B-cell depletion therapy, in Sjögren’s syndrome (SS) have shown mixed results with regard to salivary secretion rate. In addition, little research has been conducted into the effect on saliva composition and its association with histopathological parameters of SS. Such analyses can provide insight into the effect of rituximab on the possible recovery of salivary gland function. The question for this study is: “To what extent does treatment with rituximab have an effect on saliva composition in patients with Sjögren’s syndrome?” Methods This retrospective study is based on an existing rituximab cohort. In this cohort, the effect of rituximab was investigated in a placebo-controlled, double-blind, randomized, prospective design. Of twenty rituximab-treated and ten placebo-treated patients, salivary flow rates (unstimulated total saliva (UWS), stimulated total saliva (SWS), unstimulated submandibular/sublingual saliva (uSM/SL), stimulated submandibular/sublingual saliva (sSM/SL) and stimulated parotid saliva (sPar)), salivary components of sPar (concentrations of Na+, K+, Cl-, PO43-, total protein and amylase) and the histopathological parameters of parotid biopsies (total amount of infiltrate ( CD45+), B-lymphocyte count (CD20+) and T-lymphocyte count (CD3+)) were determined at baseline (T0) and after twelve weeks (T1). Within the rituximab group, distinction was made via EULAR Sjögen’s Syndrome Disease Activity Index (ESSDAI) to discriminate between responders and non-responders to rituximab treatment. Statistical analysis of the sialometric, sialochemical and histopathological findings were performed using Mann-Whitney U- and Wilcoxon Signed Rank-tests, comparing the rituximab and placebo groups and the clinical responders (decrease in ESSDAI score of ≥3 points at twelve weeks compared to baseline) and non-responders (change in ESSDAI score of <3). In addition, the association between Na+ and the histopathological parameters was examined by single and multiple linear regression analysis. Results This study shows that treatment with rituximab in pSS patients improved the salivary secretion rate of UWS (p=0.05) after twelve weeks, while in the placebo group the SWS and sPar decreased (p<0.05). Also after twelve weeks, a difference has been demonstrated between the rituximab and placebo groups for SWS and sPar (p<0.05). Sialochemical analysis of sPar revealed no significant differences at week twelve and between the rituximab and placebo groups. It was observed that the concentration of Na+ tended to decrease in the rituximab group, but not in the placebogroup. A comparison between the responder and non-responder groups also showed that the concentration of Na+ in the responder group tended to decrease more than in the non-responders. A decrease in the number of CD20+ cells was observed for both the rituximab group and the responder group (p=0.001, p<0.05). This decrease did not occur in the placebo group and the non-responder group. No relationship could be demonstrated between the concentration of Na+ and any of the histopathological parameters (CD45+, CD20+ and CD3+). Discussion It can be concluded from the results that treatment with rituximab has no clear effect on saliva composition in pSS. However, after twelve weeks, there is an improvement in saliva secretion and a decrease in the lymphocytic infiltrate. This indicates partial recovery of salivary gland function, but the damage that is already present and leading to the elevated sodium levels does not significantly improve after twelve weeks of rituximab treatment. Distinguishing between responders and non-responders using the ESSDAI score did not yield any clearer effects.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Vissink, Prof. Dr. A. and Kroese, Prof. Dr. F.G.M. |
| Faculty: | Medical Sciences |
| Date Deposited: | 18 Apr 2023 11:17 |
| Last Modified: | 18 Apr 2023 11:17 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/3474 |
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