Elevated circulating levels of the interferon-γ–induced chemokines are associated with disease activity and cutaneous manifestations in adult-onset Still’s disease

Abstract

C-X-C motif chemokine 9 (CXCL9), CXCL10, and CXCL11 are produced in response to interferon-γ (IFN-γ) and trigger inflammation with the accumulation of activated lymphocytes. It appears that these chemokines could play a role in the pathogenesis of adult-onset Still’s disease (AOSD). Therefore, we investigated the associations between the levels of these chemokine and clinical manifestations in patients with active AOSD. Serum levels of IFN-γ, CXCL9, CXCL10 and CXCL11 were determined using enzyme-linked immunosorbent assays. IFN-γ levels were higher in AOSD patients than in rheumatoid arthritis (RA) patients (p = 0.001) or healthy controls (HCs) (p = 0.032). AOSD patients also exhibited higher levels of CXCL9, CXCL10, and CXCL11 compared with RA patients (p < 0.001) and HCs (p < 0.001). In follow-up AOSD patients after treatment with corticosteroid, the levels of CXCL9, CXCL10 and CXCL11 fell significantly, whereas IFN-γ levels were not significantly different. On immunohistochemistry, the percentage of CXCL10-positive inflammatory cells was higher in skin biopsy samples from AOSD patients than in those from normal control (p = 0.012), eczema (p = 0.019), and psoriasis (p = 0.009) groups. Levels of the IFN-γ–induced chemokines, CXCL9, CXCL10 and CXCL11, were elevated and correlated with several disease activity markers. These interferon-γ–induced chemokines may contribute to inflammatory responses and skin manifestations in AOSD.

PTPN22 1858C>T polymorphism is associated with increased CD154 expression and higher CD4+ T cells percentage in rheumatoid arthritis patients

“…Activated CD4+ T cells release high IFN‐γ levels; this cytokine enhances chemokine expression for leukocyte recruitment by facilitating their transfer through the endothelial layer, increases antigen presentation, and promotes Th1 differentiation, all of these functions are preponderant in the pathophysiology of RA. We observed a borderline significant increase in the IFN‐γ serum levels of RA patients in relation to CS, which is in agreement with previous studies …”

“…We observed a borderline significant increase in the IFN-γ serum levels of RA patients in relation to CS, which is in agreement with previous studies. 37,38 Respecting to 1858C>T genotype, we observed that in the RA group, the presence of the risk allele favors a significant decrease in IFN-γ but intriguingly, in CS it is associated with an increase in IFN-γ levels. In this respect, a group of researchers documented that after in vitro antigen stimulation, CD4 + T cells from healthy donors carriers of 1858 T risk allele produced significantly higher amounts of IFN-γ and TNF-α than subjects carrying wild-type allele.…”

Severe pyrexia from nivolumab‐resistant advanced melanoma after successful combined therapy with encorafenib plus binimetinib

“…To investigate the soluble factors that may correlate with the onset of fever spike, we measured sCD163, CXCL9, CXCL10 and CXCL11 before and after the administration of E + B combined therapy at the time of onset of a fever spike. These soluble factors were reported to correlate with the AE of anti‐PD‐1 antibody 6,10 and with the spike of fever in patients with AOSD 5 . Serum sCD163, CXCL9, CXCL10 and CXCL11 were increased in all three cases in parallel with their fever spike, but not in another three patients who had been treated with immune checkpoint inhibitors previously but did not develop pyrexia by E + B combined therapy (Fig.…”

“…Spike of fever is a well‐known symptom in AOSD 5 . Recently, sCD163 and IFN‐γ‐induced chemokines (CXCL9, CXCL10 and CXCL11) have been reported to correlate with the onset of pyrexia in AOSD 5,6 .…”

“…In this report, we describe three cases of advanced melanoma treated with E + B combined therapy, followed by anti‐programmed death 1 (PD‐1) antibody monotherapy. In addition, we investigated the serum levels of soluble (s)CD163, C‐X‐C motif chemokine (CXCL)9, CXCL10 and CXCL11, which have been reported to be biomarkers of adult‐onset Still’s disease (AOSD) 5,6 …”