ABSTRACT Objectives To assess belimumab efficacy in patients from North East Asia (NEA) with systemic lupus erythematosus (SLE) in baseline demographic/disease characteristic subgroups. Methods This analysis of patient subgroups from BLISS-NEA (GSK Study 113750; NCT01345253) studied adults with SLE randomized to belimumab (10 mg/kg intravenous) or placebo. Primary endpoint, SLE Responder Index 4 (SRI-4) response rate at Week 52, was analysed in subgroups defined by gender, country, prednisone-equivalent dose, concomitant medications, Safety of Estrogens in Lupus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score, complement (C) levels, anti-double-stranded deoxyribonucleic acid (dsDNA) positivity, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score. Results Patients (overall population: N = 677; belimumab: n = 451, placebo: n = 226) were from China (76.4%), Korea (14.8%), and Japan (8.9%). The mean age was 32.1 years; 92.9% were female. In the overall population, more belimumab (53.8%) than placebo (40.1%) patients were SRI-4 Week 52 responders (p = .0001). SRI-4 response rates by subgroups were generally consistent with the overall population. A greater response with belimumab was seen in patients with a baseline SELENA-SLEDAI score ≥10 versus ≤9 and patients with low C3/C4 levels and anti-dsDNA positive at baseline versus those ‘NOT’ (low C3 and/or C4 and anti-dsDNA positive). Conclusions These findings continue to support the efficacy of belimumab in SLE.
Dermatomyositis (DM) is an autoimmune disease affecting primarily the skin, muscle and lung. Dysregulations of cytokines and chemokines are commonly found in inflammatory disorders.To investigate the association between serum cytokines and chemokines and clinical severity, especially cutaneous lesions and interstitial lung disease (ILD) in patients with DM and clinically amyopathic DM (CADM).Clinical features, laboratory findings and serum of 40 patients with DM or CADM were collected and analysed. Serum cytokines and chemokines were measured by enzyme-linked immunosorbent assay or cytometric bead array. A multiple unpaired t-test was performed to compare cytokines and chemokines in patients with DM and healthy controls. Correlations of serum cytokines and chemokines with disease severity were evaluated by Spearman's rank correlation test.Serum interferon (IFN)-β [rs = 0·37, 95% confidence interval (CI) 0·078-0·62; P = 0·019] and CXCL10 (rs = 0·32, 95% CI to -0·004 to 0·57; P = 0·045) were significantly correlated with the Cutaneous Dermatomyositis Disease Area and Severity Index activity score in the subset of patients with DM or CADM. Serum levels of interleukin (IL)-6, IL-10, IL-18 and IFN-β were significantly higher in the patients with acute/subacute interstitial pneumonia (A/SIP) than in the subset without A/SIP (P < 0·05). IL-6 (rs = 0·54, 95% CI 0·27-0·72; P < 0·001) and IL-18 (rs = 0·46, 95% CI 0·21-0·65; P = 0·003) were significantly correlated with the serum level of anti-melanoma differentiation-associated protein 5 antibody.Serum levels of IFN-β and CXCL10 may be useful biomarkers for assessing cutaneous disease activity in patients with DM and CADM. In addition, serum IL-6, IL-10, IL-18 and IFN-β were highly correlated with the occurrence of A/SIP. These cytokines may play a role in the pathogenesis of DM and CADM.
Objective
To determine serum ferritin levels in patients with idiopathic inflammatory myopathies(IIM), including dermatomyositis(DM), clinical amyopathic dermatomyositis(CADM)and polymyositis(PM), and to evaluate their association with disease activity, especially with interstitial lung disease(ILD).
Methods
Clinical data and laboratory results were collected from 120 patients with IIM. A double-site enzyme immunoassay was conducted to measure serum ferritin levels in 120 patients with IIM and 63 healthy human controls. Statistical analysis was carried out to assess the relationship of serum ferritin levels with inflammatory biomarkers, autoantibodies, serum muscle enzymes, and severity of ILD in patients with IIM.
Results
Serum ferritin levels were elevated in 36 out of the 120 patients, but normal in the other 84 patients. Compared with patients with normal serum ferritin levels, those with elevated serum ferritin levels showed increased levels of C-reactive protein(14.1 ± 6.5 vs. 3.6 ± 1.7 mg/L, P < 0.01), aspartate aminotransferase(111.8 ± 44.6 vs. 46.0 ± 9.0 U/L, P< 0.01), lactate dehydrogenase(388.6 ± 81.5 vs. 260.7 ± 29.1 U/L, P< 0.01), as well as erythrocyte sedimentation rate(34.8 ± 8.2 vs. 15.4 ± 2.7 mm/h, P< 0.01). However, no significant difference was observed in the level of creatine kinase between patients with elevated and normal serum ferritin levels. Moreover, serum ferritin levels were significantly higher in both IIM patients complicated with acute/subacute interstitial pneumonia(A/SIP, 650.5 ± 268.5 ng/ml)and those with chronic interstitial pneumonia(CIP, 489.9 ± 157.3 ng/ml)than in those without ILD(155.7 ± 90.8 ng/ml)and those with imageological changes but no clinical symptoms of ILD(193.3 ± 62.1 ng/ml)(all P < 0.01). Moreover, compared with patients with normal serum ferritin levels, those with elevated serum ferritin levels showed a significant increase in the incidence of CIP(52.8% vs. 25.9%, P < 0.01), A/SIP(22.2% vs. 3.5%, P < 0.01), as well as appearance of ground-glass opacity(67.6% vs. 43.4%, P < 0.05)and honeycomb-like changes(14.7% vs. 2.6%, P < 0.05)on high-resolution CT scans.
Conclusion
Serum ferritin levels are highly correlated with erythrocyte sedimentation rate, C-reactive protein, aspartate aminotransferase, lactate dehydrogenase, ILD and high-resolution CT findings, and may be of great clinical significance for the evaluation of disease activity, especially the severity of ILD.
Key words:
Myositis; Dermatomyositis; Ferritins; Lung diseases, interstitial; Idiopathic interstitial pneumonias
Objective
To explore the association of serum cytokine levels with disease activity in patients with dermatomyositis (DM) and clinically amyopathic dermatomyositis (CADM) , especially their association with skin lesions and interstitial lung disease (ILD) .
Methods
Enzyme-linked immunosorbent assay (ELISA) and cytometric beads array (CBA) were performed to detect the serum levels of interleukin (IL) -2, IL-4, IL-6, IL-10, IL-17A, IL-18, tumor necrosis factor (TNF) and interferon (IFN) -γ in 40 patients with DM or CADM, as well as in 16 health checkup examinees (healthy control group) . Then, the association of serum cytokine levels with skin lesions, inflammatory biomarkers and severity of ILD was analyzed.
Results
The patients with DM/CADM showed significantly higher serum levels of IL-6 (37.8 ± 45.8 pg/ml) , IL-10 (16.1 ± 7.2 pg/ml) and IL-18 (492.0 ± 193.1 pg/ml) compared with the healthy controls (12.0 ± 2.7 pg/ml, 7.7 ± 1.4 pg/ml, 191.1 ± 39.2 pg/ml, respectively, all P < 0.001) , and there were no significant differences in the serum levels of the other 5 cytokines between the above 2 groups. The serum level of IL-6 was significantly higher in patients with elevated erythrocyte sedimentation rate (ESR) than in those with normal ESR (49.7 ± 46.8 pg/ml vs. 29.1 ± 45.4 pg/ml, P= 0.008) . The patients with raised C-reactive protein (CRP) levels showed significantly higher serum levels of IL-6 (68.7 ± 59.7 pg/ml) and IL-18 (635.1 ± 232.8 pg/ml) compared with those with normal CRP levels (IL-6: 30.6 ± 40.3 pg/ml, P= 0.013; IL-18: 440.2 ± 164.7 pg/ml, P= 0.020) . Moreover, the patients with elevated levels of lactate dehydrogenase (LDH) showed significantly higher serum levels of IL-10 (18.4 ± 6.9 pg/ml) , IL-17A (19.6 ± 6.7 pg/ml) and IL-18 (529.4 ± 197.2 pg/ml) compared with those with normal LDH levels (IL-10: 10.7 ± 4.8 pg/ml, P < 0.001; IL-17A: 11.4 ± 6.6 pg/ml, P= 0.001; IL-18: 404.9 ± 158.0 pg/ml, P= 0.037) . No significant difference in the cytokine levels was observed between the patients with elevated creatine kinase (CK) levels and those with normal CK levels. The patients with Gottron′s papules/sign showed significantly higher serum levels of IL-18 (513.7 ± 187.2 pg/ml) compared with those without Gottron′s papules/sign (297.1 ± 140.4 pg/ml, P < 0.05) . The serum levels of IL-10 and IL-18 were significantly higher in the patients with DM/CADM complicated by ILD (18.0 ± 6.7 pg/ml, 552.3 ± 192.8 pg/ml, respectively) than in those without ILD (11.6 ± 6.5 pg/ml, 351.4 ± 101.0 pg/ml, respectively, both P= 0.001) .
Conclusion
Serum levels of IL-6, IL-10 and IL-18 are highly associated with inflammatory biomarkers, skin lesions and ILD in patients with DM/CADM.
Key words:
Dermatomyositis; Cytokines; Lung Diseases, Interstitial; Interstitial lung disease; Clinically amyopathic dermatomyositis
To investigate the clinical features of dermatomyositis (DM) and clinically amyopathic DM (CADM) patients with the presence of anti-melanoma differentiation-associated gene 5 (anti-MDA-5) antibodies.We screened the serum anti-MDA-5 antibody levels of 140 patients with various connective tissue diseases (CTDs), including 32 with DM and 32 with CADM, or idiopathic pulmonary fibrosis (IPF). The clinical courses of DM/CADM patients with a positive expression of anti-MDA-5 antibodies were delineated.Anti-MDA-5 antibodies were detected at a significantly higher frequency in CADM patients than in DM patients (12 of 32 versus 3 of 32; P = 0.016), but were not detected in patients with other CTDs or IPF and healthy controls. Patients with a positive expression of anti-MDA-5 antibodies developed significantly more skin ulcerations (12 of 15 versus 4 of 49; P < 0.001) and interstitial lung disease (ILD; 15 of 15 versus 31 of 49 [P = 0.003]) than those without anti-MDA-5 antibodies. High-resolution computed tomography scores of the MDA-5-positive subset were increased compared with the MDA-5-negative group (mean ± SD 117.7 ± 76.3 versus 54.4 ± 50.7; P = 0.004), and the scores correlated well with anti-MDA-5 antibody levels (r(2) = 0.582, P = 0.029). The respiratory symptoms as well as skin ulcerations were dramatically improved in patients with anti-MDA-5 antibody levels <500 units/ml after treatment, whereas patients with anti-MDA-5 antibody levels >500 units/ml were resistant to the treatment and died of respiratory failure in a short period of time.Anti-MDA-5 antibody levels closely correlate with the severity of skin ulcerations, ILD, and the prognosis of the disease. Dynamic observation of serum anti-MDA-5 antibody levels would be helpful in predicting the course of ILD and facilitating better therapeutic targeting.
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