Objective: 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.Methods: 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.Results: 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 (r² = 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 were resistant to the treatment and died of respiratory failure in a short period of time.Conclusion: 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.

Pemphigus is a complex dermatologic autoimmune bullous disease whose pathogenic mechanism is not fully understood. Anti-desmoglein-1 (Dsg1) and anti- Dsg3 autoantibodies play an important role in the pathogenesis of pemphigus. To investigate the role of T-helper17 (Th17) and regulatory T (Treg) cells in the pathogenesis of pemphigus in fifty-one patients and twenty-six healthy individuals (control group). Levels of CD3(+)CD8(-) IL-17 expressing Th cells and CD4(+)CD25(hi)Foxp3(+) Treg cells were determined by FACS in both groups, along with anti-Dsg1 and Dsg3 antibody titers. An analysis of the correlation between Th17 and Treg cells was performed. Th17 cell numbers were significantly higher in pemphigus patients than in normal controls (P = 0.014), especially in the acute onset and chronic active stages (P = 0.004 and 0.022). Conversely, Treg cells in pemphigus patients were significantly fewer than in the control group (P<0.001). The same trend was observed between the acute onset and the remittent stage patients (P = 0.006). We found a negative correlation between Th17 and Treg cell populations (r = -0.532, P<0.001). Anti-Dsg1 and Dsg3 antibody titers were higher in patients in the active stage than in the remittent stage, with an increased IgG4/IgG1 subclass ratio. There was no statistically significant correlation between Th17/Treg ratios and anti-Dsg1 or Dsg3 antibody titers. These findings show an imbalance of Th17 and Treg cell populations in pemphigus patients, which might result in the activation and proliferation of effector T cells, further up-regulating B cell activity and antibody production.

Objective.: Gottron papules and Gottron sign are characteristic and possibly pathognomonic cutaneous features of classic dermatomyositis and clinically amyopathic dermatomyositis (DM/CADM). However, the Gottron papules/Gottron sign with cutaneous ulceration (ulcerative Gottron papules/Gottron sign) are less common. We aimed to clarify the clinical characteristics of patients with DM/CADM who have ulcerative Gottron papules/Gottron sign.Methods.: Clinical features, laboratory findings, and prognosis of patients with DM/CADM who had Gottron papules/Gottron sign with or without ulceration were analyzed and compared.Results.: Occurrences of acute interstitial pneumonia/subacute interstitial pneumonia (AIP/SIP) were significantly higher in patients with ulcerative Gottron papules/Gottron sign (19/26) versus patients with Gottron papules/Gottron sign without ulceration (2/66, p < 0.001). We also observed that the white blood cell counts (mean ± SD 4.2 ± 1.6 vs 6.9 ± 2.9; p < 0.001) and creatine kinase (CK) levels (198.0 ± 377.7 vs 1364.0 ± 2477.0; p = 0.019) were significantly lower, whereas the positive rate of antimelanoma differentiation-associated gene 5 antibody (anti-MDA5; 88.5% vs 6.1%, p < 0.001) and serum ferritin levels (665.2 ± 433.5 vs 256.2 ± 279.0, p < 0.001) were significantly higher in the patients with ulcerative Gottron papules/Gottron sign. Moreover, the cumulative survival rate of the group with ulcerative Gottron papules/Gottron sign was significantly lower (p < 0.001).Conclusion.: Patients with DM/CADM who have ulcerative Gottron papules/Gottron sign, positive anti-MDA5 antibody, and significantly lower baseline CK level are at increased risk of interstitial lung disease, especially AIP/SIP. A new designation for this subgroup of patients should be established to draw more attention to this clinical entity.

Background/Aims: Acute and chronic leukemia are severe malignant cancers worldwide, and can occur in pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia (PL) remains challenging. Autophagy is essential for the regulation of cell survival in the harsh environment. However, the role of autophagy in the survival of PL cells under the oxidative stress, e.g. chemotherapy, remain ill-defined. In the current study, we addressed these questions. Methods: We analyzed the effects of oxidative stress on the cell viability of PL cells in vitro, using a CCK-8 assay. We analyzed the effects of oxidative stress on the apoptosis and autophagy of PL cells. We analyzed the levels of Beclin-1 and microRNA-93 (miR-93) in PL cells. Prediction of binding between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The relationship between levels of miR-93 and patients' survival was analyzed in PL patients. Results: We found that oxidative stress dose-dependently increased autophagy in PL cells. While low-level oxidative stress did not increase apoptosis, high-level oxidative stress increased apoptosis, seemingly from failure of autophagy-mediated cell survival. High-level oxidative stress appeared to suppress the protein levels of an autophagy protein Beclin-1 in PL cells, possibly through induction of miR-93, which inhibited the translation of Beclin-1 mRNA via 3'-UTR binding. Conclusion: Beclin-1-mediated autophagy plays a key role in the survival of PL cells against oxidative stress. Induction of miR-93 may increase the sensitivity of PL cells to oxidative stress during chemotherapy to improve therapeutic outcome.