Background/Purpose

CXCL4 is a pleiotropic antiangiogenic and immunomodulatory chemokine. We aimed to investigate CXCL4 serum levels in primary Sjögren’s syndrome (pSS) and looked for associations with disease features, with a focus on parameters of microvascular involvement.

Methods

Thirty-nine consecutive pSS patients meeting the 2012 classification criteria for the disease were enrolled and underwent clinical assessment, nailfold videocapillaroscopy (NVC), and autoantibody profiling. Additional serum to measure levels of CXCL4 and soluble E-selectin (sE-selectin) was available from 36 pSS patients and 30 healthy controls (HC). At NVC, enlargement, density, and tortuosity of capillaries, and microhemorrhages were scored on a 0 to 3 scale (0 = normal, 3 = high grade). Plexus visualization and neoangiogenesis were also considered as present/absent. Autoantibodies were assayed by ELISA, while CXCL4 and sE-selectin were measured by multiplex suspension immunoassay. 

Results

Serum levels of CXCL4 were increased in pSS patients (median 1.79 ng/ml [0.2-11.18], vs 1.023 ng/ml [0.02-14.45] in HC, p < 0.05), the highest found in anti-La/SSB autoantibody-negative patients (2.89 mg/ml [1.01-11.18] vs 1.69 [0.2-2.72] ng/ml, p < 0.05), and correlating with a longer disease duration (r = 0.35, p < 0.05). Most interestingly, we found a higher prevalence of CXCL4 levels above the 95° percentile of the HC group (10.91 ng/ml) in pSS patients with Raynaud’s phenomenon (RP) (11/14 vs 4/18, p < 0.001). This prompted us to look for associations of serum CXCL4 with microvascular abnormalities at NVC and/or correlations with serum levels of sE-selectin, a marker of endothelial activation. Indeed CXCL4 positively correlated with sE-selectin (r = 0.45, p < 0.01), but was not associated with any NVC finding. However, a reduced capillary density and high grade enlarged capillaries were more prevalent in patients with RP (14/15 vs 6/21 and 16/16 vs 8/23, respectively; both p < 0.0001). An NVC “scleroderma pattern” was observed only in 3 patients (megacapillaries), and neoangiogenesis in 2 (both p > 0.05).

Conclusion

Here we show for the first time that pSS patients have increased serum CXCL4 levels, which correlate with disease duration and serum sE-selectin  levels, and are associated with the presence of RP. These data suggest that CXCL4 might be implicated in microvascular/endothelial impairment in pSS. Actually, our pSS patients with RP had microvascular damage, as a reduced capillary density and high grade enlarged capillaries showed. Lastly, we detected higher CXCL4 levels in anti-La/SSB autoantibody-negative patients. This negative association might be related to the role played by pSS specific autoantibodies in promoting pathological angiogenesis in human salivary glands. Taken together this data provide preliminary evidence of a role for circulating CXCL4 as a marker of microvascular damage in pSS on larger cohorts of patients.

---

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-cxcl4-is-increased-in-patients-with-primary-sjogrens-syndrome-and-is-associated-with-features-of-microvascular-impairment/