Session Title: Sjögren's Syndrome: Clinical Aspects
Session Type: Abstract Submissions (ACR)
To address the change in labial salivary gland (LSG) inflammation after Belimumab (biological treatment inhibiting soluble BAFF/BLyS) therapy in pSS patients and identify predictor of response to treatment.
Patients were included in 2 parallel and identical studies in 2 European centers. Patients had to fulfill AECGcriteria, to be anti-SSA/SSB positive and had to have at the time of inclusion either systemic complications or early disease (<5 yrs of symptoms), or the presence of biomarker of B-cell activation. The patients were treated with belimumab 10 mg/kg W0, W2, W4 and then every four weeks until W24. Minor labial salivary gland (LSG) biopsies of the 15 patients (all female, mean age=50 yrs, mean disease duration= 5 yrs)from the French center, performed at W0 and W28, were analyzed for estimating the focus score, the B-cell/T-cell ratio, BAFF expression and NK infiltrate .
Response to treatment was defined according to a composite primary end-point and systemic response according to a decrease of the ESSDAI≥3 points.
Before treatment, significant lymphocytic sialadenitis (focus score >1) was observed in 11 (78.6%) patients, five of whom became negative at w28 (p=0.07). The median focus score decreased from 1.6 to 0.5 (p=0.39) and Chisholm score from 4 to 2 (p=0.01). Median B-cell /T cell ratio decreased decreased from 0.58 to 0.50, p=0.055. Before treatment, a BAFF staining was detected in 11/14 (78.6%) patients, and in only 7/14 (50.0%) after belimumab (p=0.07). The median percentage of BAFF positive cells in foci significantly decreased from 27.5% to 5% after belimumab therapy (p=0.03).NKp46 staining revealed that NK cells infiltrate was predominantly located in interstitium rather than in foci (p=0.0003), and did not change after belimumab.
8/15 patients (53%) achieved the primary end-point, and 6 (40%) patients had a significant systemic improvement. The only histological parameter associated with response to belimumab was the NK infiltrate in periphery of the foci which was lower in responders than in non-responders (median number of NK cells 21.4 vs 29.4 ; p=0.028) Also, there was a trend to observe lower focus score in responders than in non responders (median number of foci 1.37 vs. 3.0; p=0.08). Likewise, low NK infiltrate was also associated with improvement of systemic activity (p=0.019). The rate of salivary BAFF-positive cells was not associated with the response. Dosage of serum BAFF levels and their association to response to belimumab will be presented at the meeting.
After belimumab therapy, there was a clear tendency in favour of a decrease of lymphocytic infiltration BAFF-expressing cells and of B-cell/T-cell ratio within LSG. Also the percentage of BAFF positive cells significantly decreased, that could be interpreted as a decrease of the BAFF expressing cells, but also as a decrease in B cells expressing BAFF receptors linked to soluble BAFF passively stained by the anti-BAFF antibody.
The patients with a higher number of foci and a higher number of NK cells at the periphery of the foci had a poor response to Belimumab, suggesting that these forms of the disease may be more linked to the IL-12/IFNg TH1/ NK axis and less linked to BAFF/B-cell axis than others
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/salivary-gland-lymphocyte-pattern-associated-with-response-to-belimumab-in-primary-sjogrenssyndrome-results-of-the-beliss-study/