Serum CXCL4 increase in primary Sjögren’s syndrome characterizes patients with microvascular involvement and reduced salivary gland infiltration and lymph node involvement

Abstract

CXCL4 is an antiangiogenic and immunomodulatory chemokine. We aimed to investigate serum levels of CXCL4 in primary Sjögren's syndrome (pSS), looking for associations with disease features. Thirty-nine consecutive pSS patients underwent clinical-serological assessment and nailfold videocapillaroscopy (NVC). Thirty-six patients and 30 controls affected by osteoarthritis were also investigated for serum levels of CXCL4 and soluble E-selectin (sE-selectin). CXCL4 was higher in pSS patients than in controls (1.79 [0.2-11.18] vs 1.023 ng/ml [0.02-14.45], p < 0.05), particularly in those without anti-La/SSB antibodies (2.89 [1.01-11.18] vs 1.69 ng/ml [0.2-2.72], p < 0.05), while it was lower in pSS patients with a focus score ≥1 at lip biopsy (1.44 [0.86-2.1] vs 2.24 ng/ml [1.64-3.25], p < 0.05) and clinically evident lymphadenopathy (1.53 [0.38-1.7] vs 2.08 ng/ml [1.45-3.03], p < 0.05). CXCL4 correlated with disease duration (r = 0.35, p < 0.05) and sE-selectin (r = 0.45, p < 0.01). Patients with Raynaud's phenomenon (RP) had more frequently abnormal CXCL4 levels than patients without RP (11/15 vs 3/21, p < 0.001), enlarged capillaries (14/16 vs 7/23, p < 0.001) and capillary loss at NVC (14/16 vs 6/23, p < 0.001). The hitherto unknown association of increased serum CXCL4 with features of microvascular impairment in pSS, along with the negative association with features of lymphocytic response (i.e., the absence of subset disease-specific autoantibodies, a low focus score, and the absence of lymphadenopathy) suggest clarifying the possible implication of this chemokine in pSS pathogenesis in larger studies.

CXCL4 assembles DNA into liquid crystalline complexes to amplify TLR9-mediated interferon-α production in systemic sclerosis

“…For isolation of human peripheral blood pDCs, blood buffy coats of healthy donors (HD) were obtained from “Centre de Transfusion sanguine of Hopitaux Universitaire”, Geneva, CH, and Blood Center of Policlinico Umberto I, Rome, IT. After separation of PBMCs by Ficoll centrifugation, pDCs were purified as described 23,41 by using Diamond Plasmacytoid Dendritic Cell Isolation Kit (Miltenyi Biotec). Cell purity was evaluated by staining the cells with anti-CD123-APC and anti-HLADR-PerCPcy5.5 antibodies (both from BD Pharmingen) and flow cytometry acquisition (Supplementary Fig.…”

CXCL4 is a novel inducer of human Th17 cells and correlates with IL‐17 and IL‐22 in psoriatic arthritis

“…Besides the crucial role of CXCL4 in maintaining homeostasis, it has been implicated in many inflammatory conditions [11]. We and others reported elevated levels of CXCL4 in various Th17associated rheumatic diseases [12][13][14][15][16], yet the role of CXCL4 in driving the Th17 pathway is largely unexplored. While it has been indicated previously that blocking CXCL4 in human platelet-CD4 + T cells co-cultures led to a reduction of IL-17 production [17,18], direct effects of CXCL4 on Th17 responses have never been studied.…”

Characterisation of macrophage infiltration and polarisation based on integrated transcriptomic and histological analyses in Primary Sjögren’s syndrome

“…This finding indicates that inflammatory macrophages may interact with damaged vessels in pSS. Upregulated serum CXCL4 in patients with pSS inhibits endothelial cell proliferation, which is closely related to microvascular injury (73). Macrophages produce vascular endothelial growth factor-A (VEGF-A), stimulating angiogenesis during chronic inflammation (74).…”