Background/Purpose:

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.

Methods:

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.

Results:

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.

 Conclusion:

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/