Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic sclerosis (SSc) is a rare multisystem connective tissue disease characterized by skin and internal organs fibrosis and vascular abnormalities, along with the presence of autoantibodies. Basophils, which have long been associated with allergy and parasitic infections, are now identified as having the ability to promote fibrosis, stimulate B cells and increase autoantibodies production. Herein we investigated the potential role of basophils in SSc.
Methods: Peripheral basophils from patients with SSc who did not receive glucocorticoids or immunosuppressants and healthy controls (HC) were analyzed using flow cytometry and basophil activation test. The impact of the KU812F basophil cell line on both B cells and fibroblasts isolated from SSc patients were assessed using flow cytometry and xCelligence assay.
Results: Sixty-five consecutive SSc patients and 38 HC were recruited. The proportion of CD203c-positive basophils was higher in SSc patients than in HC (37.5 % [24.3 – 59.0] vs 25.6% [13.6 – 41.7]; p < 0.001). Compared to HC, basophils from SSc patients had higher mean fluorescence intensity (MFI) quantifications of CD154 (854 [541 – 1334] vs 485 [147 – 871]; p < 0.05) and intracellular B cell activating factor (1551 [1001 – 4373] vs 857 [722 – 1498]; p < 0.05). Activated KU812F basophils were able to decrease the proportion of CD95-positive B cells (10.5% [8.4 – 12.6 vs 14.8% [14.4 – 21.5]; p < 0.05), to increase the production of interleukine-6 (21.2% [16.5 – 29.9] vs 14.9 [12.3– 16.7]; p < 0.05) and transforming growth factor-β (5.6% [4.7 – 7.2] vs 4.1 [2.6– 5.4]; p < 0.05) producing B cells and to enhance the proliferation of fibroblasts from patients with SSc. Lastly, the expression of CRTH2 on basophils correlated with patients’ disease characteristics and was able to discriminate those with or without pulmonary hypertension (PAH). Indeed, CRTH2 MFI quantification among basophils positively correlated with patients’ diffusing capacity of the lungs for carbon monoxide (r = 0.60, p < 0.05), negatively correlated with patients’ modified Rodnan skin score (r = – 0.77, p < 0.01) and was lower in SSc patients with PAH than in SSc patients without PAH (31476 [30213 – 31633] vs 59576 [41312 – 67788]; p < 0.001).
Conclusion: Peripheral basophils are activated and are able to simulate both B cells and fibroblasts in patients with SSc, suggesting a key role of basophils in the pathophysiology of SSc.
To cite this abstract in AMA style:Chaigne B, Dumoitier N, Regent A, Terrier B, London J, Groh M, Thieblemont N, Mouthon L. Basophils Are Activated and Stimulate Both B Cells and Fibroblasts in Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/basophils-are-activated-and-stimulate-both-b-cells-and-fibroblasts-in-systemic-sclerosis/. Accessed September 20, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/basophils-are-activated-and-stimulate-both-b-cells-and-fibroblasts-in-systemic-sclerosis/