Soluble IL-2 Receptor in Dermatomyositis: Its Associations with Skin Ulcers and Disease Activity.
To investigate the role of soluble interleukin-2R (sIL-2R) in idiopathic inflammatory myopathies (IIM).
Serum sIL-2R levels were measured in 74 dermatomyositis (DM), 16 immune-mediated necrotizing myopathy (IMNM), 24 rheumatoid arthritis (RA), 20 systemic lupus erythematosus (SLE), and 20 healthy controls (HCs) by chemiluminescent immunometric assay. Clinical features and laboratory data were collected from electronic medical record. Disease activity was evaluated by using physician global disease activity and myositis disease activity assessment visual analog scale (MYOACT) on admission. 20 DM patients were followed. Serum sIL-2R levels were analyzed and compared with clinical features, laboratory data, and measures of disease activity.
Serum sIL-2R levels were significantly higher in DM patients than in IMNM patients and HCs (648.8 ± 433.1 U/ml vs. 352.3 ± 126.0 U/ml and 648.8 ± 433.1 U/ml vs. 285.8 ± 101.9 U/ml, respectively; all P < 0.001), while there was no significant difference between IMNM and HCs. There were also no significant differences of sIL-2R levels in DM, SLE, and RA. Importantly, serum sIL-2R levels were significantly higher in treatment-naïve or active DM patients than those that are not (1100.9 ± 550.4 U/ml vs. 615.6 ± 330.4 U/ml, P = 0.006; 808.8 ± 421.6 U/ml vs. 339.8 ± 103.4 U/ml, P < 0.001). DM patients with skin ulcers had significantly higher sIL-2R levels than those without (889.3 ± 509.9 U/ml vs. 640.0 ± 368.7 U/ml, P = 0.023). Cross-sectional analysis in DM showed that sIL-2R levels positively correlated with CK, ESR, CRP, ferritin, physician VAS, and MYOACT scores (rho = 0.278, rho = 0.474, rho = 0.469, rho = 0.454, r = 0.646, and r = 0.600, respectively; all P < 0.05), negatively correlated with T cell counts and MMT8 scores (r = -0.380, P = 0.002; rho = -0.394, P = 0.001). Follow-up study showed that changes in sIL-2R levels after treatment correlated with changes in physician VAS and MYOACT scores (r = 0.823 and r = 0.695, respectively; all P < 0.01).
Serum sIL-2R levels were elevated in DM but not in IMNM. Serum sIL-2R could act as a disease activity marker and be associated with ulcerative skin lesions in DM.
He L
,Shu X
,Liu X
,Ge Y
,Li S
,Lu X
,Wang G
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Increased serum soluble interleukin-2 receptor levels in dermatomyositis are associated with Th17/Treg immune imbalance.
Dermatomyositis (DM) represents a multifaceted chronic inflammatory myopathy, primarily manifesting as progressive deterioration of muscular and cutaneous tissues. Despite an incomplete comprehension of DM's etiology and pathogenesis, current evidence implicates the involvement of T lymphocyte infiltration, extensive cytokine release, myositis-specific antibodies, and myositis-associated antibodies in disease development. Serum soluble interleukin-2 receptor (sIL-2R) frequently serves as a marker for T cell activation; however, its role remains elusive. Consequently, this investigation sought to elucidate the association between sIL-2R levels, peripheral blood lymphocyte subset counts, and related cytokines in DM patients, with the aim of uncovering the intricate mechanisms underlying DM and establishing a theoretical foundation for the implementation of precise, targeted, individualized immunomodulatory therapy. In this study, a cohort of 60 dermatomyositis (DM) patients, comprising 32 with inactive DM and 28 with active DM, was enrolled and stratified into inactive and active groups based on the Myositis Disease Activity Visual Analogue Scale (MYOACT). Flow cytometry was employed to quantify the absolute counts of peripheral lymphocyte subsets and CD4+T cell subsets in each group, while a flow cytometry bead array was utilized to measure serum cytokine levels. In a comparative analysis between healthy individuals and patients diagnosed with DM, we observed a marked elevation in serum sIL-2R concentrations (P < 0.001) and T-helper 17 cell/regulatory T cell (Th17/Treg) ratios (P < 0.01) within the latter group. A positive correlation was identified between serum sIL-2R levels and various parameters, including ESR, CRP, VAS, AST, CKMB, LDH, HBDH, PT, APTT, DDi, IL-6, IL-10, and IFN-γlevels (P < 0.05). In contrast, serum sIL-2R levels demonstrated a negative correlation with LY, HGB, ALB, Th17 cell populations, and Th17/Treg cell ratios (P < 0.05). Employing multivariate logistic regression, we identified serum sIL-2R concentrations as an independent risk factor for both disease activity and hepatic involvement in DM patients. Moreover, receiver operating characteristic (ROC) curve analyses revealed that serum sIL-2R levels significantly contributed to the differentiation of disease activity and the detection of liver involvement in DM patients, with areas under the ROC curve (AUC) of 0.757 (95% CI 0.630-0.884, P = 0.001) and 0.826 (95% CI 0.717-0.935, P < 0.001), respectively. This study highlights the potential utility of serum sIL-2R levels as a valuable biomarker for assessing disease activity and liver involvement in dermatomyositis. Elevated serum concentrations of sIL-2R were observed in patients with DM, exhibiting significant associations with Th17 cell populations and Th17/ Treg ratios. These findings indicate that sIL-2R may be implicated in the immunopathogenesis of DM, thereby warranting further investigation to elucidate its role in the disease process.
Xie Y
,Zhang T
,Su R
,Liu L
,Jiang L
,Xue H
,Gao C
,Li X
,Wang C
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