Distribution of anti-melanoma differentiation associated gene 5 (MDA5) IgG subclasses in MDA5+ dermatomyositis.

OBJECTIVES: The anti-melanoma differentiation-associated gene 5 (MDA5) antibody is the main predictor of interstitial lung disease (ILD) in DM and clinically amyopathic DM (CADM). Nevertheless, a subset of MDA5+ patients have a favourable prognosis. We aimed to determine the possibility of using anti-MDA5 antibody isotypes and IgG subclasses for evaluating ILD risk. METHODS: The isotypes (IgG, IgA and IgM) of anti-MDA5 were detected in serum samples of 36 anti-MDA5+ patients with DM/CADM using ELISA. IgG subclasses of anti-MDA5 antibodies were further investigated. Laboratory findings and cumulative survival were analysed based on the isotypes of anti-MDA5 and subclasses of anti-MDA5 IgG. RESULTS: Among the MDA5+ patients with DM/CADM, the positive rates of anti-MDA5 IgG, IgA and IgM were 100, 97 and 6%, respectively. The positive rates of anti-MDA5 IgG1, IgG2, IgG3 and IgG4 were 72, 25, 0 and 28%, respectively. The incidence of acute interstitial pneumonia, mortality rate and serum ferritin were significantly higher in anti-MDA5 IgG1+ patients than in anti-MDA5 IgG1- patients with DM/CADM (P = 0.0027, 0.015, 0.0011, respectively). The sensitivity and specificity of anti-MDA5 IgG1 for predicting mortality were 100 and 41.7%, respectively. A combination of anti-MDA5 IgG1 and IgG4 for predicting mortality yielded better specificity (87.5%). CONCLUSION: IgA and IgG are the primary anti-MDA5 antibody isotypes. Anti-MDA5 IgG1 is the primary component of MDA5 IgG subclasses and anti-MDA5 IgG1 and IgG4 might serve as useful biomarkers for predicting mortality in DM-ILD.

Local immune microenvironment of skin may play an important role in the development of pretibial myxedema.

Pretibial myxedema (PTM), characterized by the accumulation of glycosaminoglycans in dermis is an autoimmune skin disorder, which is almost always associated with Graves' disease (GD). Although fibroblast stimulated by thyroid-stimulating hormone receptor (TSHR) antibody, cytokines and growth factors have been postulated as target of the autoimmune process in the dermopathy, the pathogenesis of PTM remains unclear. We hypothesize that the local immune microenvironment of the skin including the antigens and antibodies, T cells, B cells, plasma cells and fibroblasts may play an important role in the development of PTM. Results obtained on PTM patients indicate increased thyroid-stimulating hormone receptor antibodies (TRAb) in the blood positively correlate with the dermal thickness of the lesions. Further analysis shows that there were more CD3+ T cells and CD20+ B cells in the skin lesions. These T and B cells are in close contact, indicating that inducible skin-associated lymphoid tissue (iSALT) may be formed in the area. In addition, we found that the infiltrating plasma cells can secrete TRAb, proving that B cells in the skin other than the thyroid are an additional source of TSHR antibodies. Meanwhile, the T and B cells in the skin or skin homogenate of patients can promote the proliferation of pretibial fibroblasts. In conclusion, our results provide evidence that the local immune microenvironment of the skin may play an important role in the development of PTM.

Local production of prolactin in lesions may play a pathogenic role in psoriatic patients and imiquimod-induced psoriasis-like mouse model.

Human prolactin (PRL) is a well-known hormone for pituitary of lactation and reproduction, but it also has immunostimulatory effect in some inflammatory or autoimmune diseases including psoriasis, which has not been well elucidated. This study aimed to determine the relationship between PRL and psoriasis through clinical case-control studies, and explore the function of PRL in the pathogenesis of imiquimod (IMQ)-induced psoriasis-like mouse model. Serum from patients with psoriasis vulgaris (PsV), patients with erythrodermic psoriasis, and healthy controls (HCs) were collected for PRL test. Skin biopsies were collected for PRL, PRL receptors (PRLRs), cytokines mRNA level determination, PRL immunohistochemistry and PRL Western blotting. Mice were divided into four groups (each n = 6): control group (CON), IMQ group, anti-PRL group and solvent group. Anti-PRL group and solvent group mice were treated with PRL antagonist (cabergoline) and the solvent (0.25% methylcellulose) separately. The serum PRL level of PsV patients was significantly higher than that of HCs (P < 0.001). Compared with HCs, the mRNA levels of PRL and Th1/Th17 cytokines in skin lesions increased significantly (P < 0.05), and the PRL protein level was also significantly elevated in the epidermis and dermis of PsV patients. In IMQ-induced psoriasis-like mouse model, the mRNA and protein levels of PRL in skin lesions were significantly higher than CON group (P < 0.01). Comparing to solvent group, serum PRL level and PRL, cytokines mRNA levels in skin lesions all decreased significantly and the skin inflammatory condition was also alleviated obviously in anti-PRL group. This study suggests that local production of PRL is the main resource of PRL in skin lesions and may play an important role in skin inflammatory of psoriasis.

Mobile emergency (surgical) hospital: Development and application in medical relief of "4.20" Lushan earthquake in Sichuan Province, China.

In the 21st century, natural disasters and emergencies occur frequently worldwide, which leads to the loss of hundreds of thousands of lives as well as the direct and indirect economic losses. China has a vast territory frequently struck by natural disasters. However, the reality is not optimistic. Poor organization and management during the rescue actions, the lack of large-scale, systematic medical rescue equipment were all great barriers to the outcomes. Mobile hospitals are expected to provide better health care. We were inspired by the concept of mobile hospital. Chongqing Emergency Medical Center, has set up trauma care system since 1988, in which prehospital care, intensive care, and in-hospital treatment is fully integrated. As a major advantage, such a system provided assurance of "golden hour" rescue treatment. Providing mobile intensive care and prehospital surgical service for severe trauma patients could reduce mortality significantly. Based on the civilian experiences in Chongqing Emergency Medical Center, the mobile emergency (surgical) hospital was developed.

Cytophagic Histiocytic Panniculitis Presenting as Subcutaneous Nodules and Generalized Edema - A Case Report.

Background: Cytophagic histiocytic panniculitis (CHP) is a rare form of nodular panniculitis characterized by clinical manifestations such as skin erythema, nodules, fever, pancytopenia, liver failure, plasmacytosis, and hepatosplenomegaly. We report a case of CHP that was initially misdiagnosed as subcutaneous panniculitis-like T-cell lymphoma (SPTCL) but achieved complete remission with a favorable prognosis. Methods: A 38-year-old female presented to the dermatology department with a 15-day history of subcutaneous nodules, generalized edema, and continuous fever. Results: The patient was diagnosed as CHP combined with hemophagocytic syndrome by typical clinical manifestations, low value of SUVmax in positron emission tomography/computed tomography (PET/CT), benign differentiated T cells, negative TCR gene rearrangement, pancytopenia, abnormal coagulation, hypertriglyceridemia, decreased NK cell count, impaired liver function, and the presence of hemophagocytic cells observed in bone biopsy smears. Conclusion: In our case, the patient presented with hemophagocytic syndrome with hemodynamic instability, indicating an intensive treatment is needed. The diagnosis of SPTCL necessitates a meticulous process of differential diagnosis, along with the cautious administration of an aggressive chemotherapy regimen. Extended follow-up is imperative to ascertain the long-term outcomes.

MicroRNA Signatures in Diagnosis and Prognosis of Cutaneous T-Cell Lymphoma.

Cutaneous T cell lymphoma (CTCL) can have clinical and histological features resembling benign inflammatory dermatosis and can be difficult to diagnose. Very limited biomarkers are available for CTCL prognosis. We aimed to identify microRNA (miR) signatures to facilitate diagnostic and prognostic evaluations of CTCL. A cross-platform miR microarray identified 10 miRs that were differentially expressed between CTCL and benign inflammatory dermatosis patients. Subsequent reverse transcription polymerase chain reaction validation was used to generate a 5-miR-based diagnosing classifier, which showed high diagnostic accuracy in CTCL (area under the curve = 0.985 and 0.956 for training and testing set, respectively). Association between miR expressions and patient prognosis was studied. miR-155 and miR-200b were significantly associated with overall survival in CTCL patients, outperformed Ki-67. miR expressions were combined with Ki-67 to create a classifier for 5-year overall survival in CTCL patients. Our work provided miR signatures to facilitate CTCL diagnosis and prognosis with satisfying accuracy.

Gottron Papules and Gottron Sign with Ulceration: A Distinctive Cutaneous Feature in a Subset of Patients with Classic Dermatomyositis and Clinically Amyopathic Dermatomyositis.

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.

SRSF1 facilitates cytosolic DNA-induced production of type I interferons recognized by RIG-I.

BACKGROUND: Evidence has shown that psoriasis is closely associated with infection; however, the mechanism of this association remains unclear. In mammalian cells, viral or bacterial infection is accompanied by the release of cytosolic DNA, which in turn triggers the production of type-I interferons (IFNs). Type I IFNs and their associated genes are significantly upregulated in psoriatic lesions. RIG-I is also highly upregulated in psoriatic lesions and is responsible for IFN production. However, RIG-I mediated regulatory signaling in psoriasis is poorly understood. METHODS: We screened a cDNA library and identified potential RIG-I interacting partners that may play a role in psoriasis. RESULTS: We found that serine/arginine-rich splicing factor 1 (SRSF1) could specifically interact with RIG-I to facilitate RIG-I mediated production of type-I IFN that is triggered by cytosolic DNA. We found SRSF1 associates with RNA polymerase III and RIG-I in a DNA-dependent manner. In addition, treatment with a TNFα inhibitor downregulated SRSF1 expression in peripheral blood mononuclear cells (PBMCs) from psoriasis vulgaris patients. DISCUSSION: Based on the abundance of pathogenic cytosolic DNA that is detected in psoriatic lesions, our finding that RIG-I interacts with SRSF1 to regulate type-I IFN production reveals a critical link regarding how cytosolic DNA specifically activates aberrant IFN expression. These data may provide new therapeutic targets for the treatment of psoriasis.

Expression of T-helper 17 cells and signal transducers in patients with psoriasis vulgaris of blood-heat syndrome and blood-stasis syndrome.

OBJECTIVE: To investigate the levels of cytokines related to T-helper (Th) 17 cells in serum and signal transducers in the psoriatic lesions of patients with psoriasis vulgaris of blood-heat syndrome (BHS) and blood-stasis syndrome (BSS). METHODS: Sixty patients with psoriasis vulgaris were divided into the BHS and BSS groups according to the syndrome differentiation of Chinese medicine (CM). Ten healthy subjects were considered as the control group. Cytokine levels of interleukin (IL)-17, IL-23 and IL-6 in serum were determined by enzyme-linked immunosorbent assay. Expression levels of signal transducer and activator of transcription 3 (STAT3), p38-mitogen-activated protein kinase (MAPK) and STAT6 in the psoriatic lesions were determined using immunohistochemistry (IHC), Western blot, and real-time quantitative reverse transcription polymerase chain reaction, respectively. RESULTS: Production of IL-17, IL-23 and IL-6 in the BHS group and BSS group were significantly increased compared with those in the control group (P<0.05). Levels of IL-17 and IL-23 in the BHS group were higher than those in the BSS group (P<0.05). Compared with the control group, IHC positive expressions and protein expressions of STAT3 and p38-MAPK, and the STAT3 mRNA expressions in the BHS and BSS groups were significantly higher (P<0.05 or P<0.01). The protein expression of STAT3 in the BHS group was significantly higher than that in the BSS group (P<0.05). CONCLUSIONS: Cytokines in serum and signal transducers in the psoriatic lesions alter with various CM syndromes of psoriasis. The results provide scientific basis for the treatment based on syndrome differentiation of CM in treating psoriasis vulgaris.

Confirmation of PSORS psoriasis susceptibility loci in a Chinese population.

We investigated 38 Chinese psoriasis families with 19 reported microsatellite markers. Families comprised a total of 96 affected and 92 unaffected individuals. Genotyping results were analyzed using parametric and nonparametric linkage analysis. Our results confirmed the published linkage with the PSORS1 locus, as well as the PSORS2 locus, which has not been previously shown in the Chinese population. Significant two-point LOD scores were obtained in a parametric linkage analysis with markers D6S1610 and D17S944. Nonparametric linkage values greater than 1.6 ( P<0.05) were obtained with markers D6S1610, D17S944 and D17S785.

[Searching for the susceptibility loci of psoriasis in Chinese].

OBJECTIVE: To search for the susceptibility genes of patients with psoriasis in Chinese. METHODS: 38 psoriasis families were determined to search for the susceptibility loci by selecting 19 reported polymorphic microsatellite DNA markers and making use of fluorescein-labeled PCR with Mega BACE sequencer. RESULTS: The significant two-point Lod score values of parametric linkage analysis were obtained with D6S1610 marker (1.18 at theta; = 0.2) and D17S944 marker (1.60 at theta; = 0.1); the NPL values greater than 1.6 (P < 0.05) of non-parametric analysis were obtained with D6S1610 marker, D17S944 marker and D17S785 marker. CONCLUSION: A putative linkage to D6S1610 marker, D17S944 marker and D17S785 marker.

Potential synergy between SNP and CpG-A or IL-1ß in regulating transcriptional activity of IL-20 promoter.

Psoriasis is a multifactorial cutaneous disorder that in many aspects is influenced by both genetic and environmental elements. IL-20, a member of IL-10 family, is found to be involved in the development of psoriasis. In our previous study, a single-nucleotide polymorphism (SNP) of IL-20-1723CG (rs1713239) was found to be associated with psoriasis progression, especially in those induced by upper respiratory tract infection. To further explore the underlying mechanism, we investigated the function of this specific variant and its cooperative effect with bacterial-like DNA or IL-1ß on regulating IL-20 expression. We found that in HaCat cells, both IL-1ß and CpG-A triggered a stronger IL-20 promoter activity with the risk-associated G allele in comparison with the nonrisk C allele of rs1713239. Furthermore, on stimulation with IL-1ß or CpG-A, an increased level of IL-20 expression was also observed in psoriatic lesions of patients carrying the risk-associated G allele. This study demonstrates that rs1713239 and infection may have potential synergetic effect on modulating the transcriptional activity of IL-20.

[Myocardial regeneration was promoted by injected Oct4 adenovirus eukaryotic expression vector].

OBJECTIVE: To construct octamer-binding transcription factor-4 (Oct4) adenoviruse eukaryotic expression vector pAV.Ex1d.-CMV>mOCT4/IRES/eGFP, and study its effect on myocardial regeneration in mice. METHODS: We constructed eukaryotic expression vector pAV.Ex1d.-CMV>mOCT4/IRES/eGFP using Gateway(R);technology and then packaged the vector with adenoviruses. After adenovirus packaging, the vector was injected into the mouse myocardium by microsyringe. The expression of Oct4 was determined by the methods of immunofluorescence and RT-PCR, and hematoxylin-eosin (HE) staining was used to detect whether the myocardial tissue was changed after the expression of Oct4. We also constructed mouse myocardial infarction model and identified the infarct area using HE staining for injecting the Oct4 adenovirus vector into the area surrounding the infarct area, Four weeks later, we detected the expression of cardiac troponin T in the infact area by Western blotting. RESULTS: Immunofluorescence showed red fluorescence indicating that Oct4 was expressed in the myocardial cell nucleus, but it could not be detected in the control group and the the control virus group. RT-PCR also proved the expression of Oct4 in Oct4 adenovirus vector group but not in the control virus group and the control group. There was no pathological changes in the myocardial tissues after Oct4 was expressed in vivo. Four weeks after the adenovirus vector was injected around the infarct area, the expression level of cardiac troponin T in Oct4 group was significantly different from that in the control group or the control empty virus group (P<0.5). CONCLUSION: Exogenous Oct4 can be expressed in the mature myocardial tissues in vivo and promote myocardial regeneration.

Propylthiouracil-induced ANCA-positive erythema nodosum treated with thalidomide.

BACKGROUND: Propylthiouracil (PTU), one of the mainstays of antithyroid therapy drugs, can lead to antineutrophil cytoplasmic antibody (ANCA) positivity and skin lesions. PTU-induced ANCA-positive vasculitis is rare and even more rare is erythema nodosum. OBJECTIVE: To report a case of a 57-year-old woman with hyperthyroidism who developed myeloperoxidase (MPO)-ANCA erythema nodosum after PTU treatment for 11 months. METHODS: Skin biopsy demonstrated septal panniculitis without vasculitis. PTU-induced ANCA-positive erythema nodosum was made. RESULTS: With discontinuation of PTU and initiation of thalidomide, skin lesions resolved completely in three weeks, and after three months, the titers of MPO-ANCA and perinuclear-ANCA (p-ANCA) had decreased remarkably. At 14-month follow-up, the patient was asymptomatic, but low levels of ANCA titers persisted. CONCLUSIONS: This report indicated that ANCA positive erythema nodosum could develop following PTU treatment. Thalidomide has been proven to be helpful and averted the adverse effects from systemic corticosteroids and other immunosuppressive drugs in this patient.