Meng Pan

Clinical manifestations of dermatomyositis and clinically amyopathic dermatomyositis patients with positive expression of anti-melanoma differentiation-associated gene 5 antibody.

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.

Impaired function of CD19+CD24hiCD38hi regulatory B cells in patients with pemphigus

Pemphigus is an organ‐specific autoimmune bullous disease.

Enhanced Proliferation and Activation of Peripheral Blood Mononuclear Cells in Patients with Psoriasis Vulgaris Mediated by Streptococcal Antigen with Bacterial DNA

Streptococcal infection is believed to have an intimate relationship with psoriasis, although the pathogenic role of streptococcal DNA is not fully understood. To gain a clearer understanding of these dynamics, we investigated the effect of streptococcal DNA on lymphocyte proliferation and activation as well as cytokine secretion in psoriasis. Peripheral blood mononuclear cells (PBMCs) from psoriatic patients had higher proliferative responses upon stimulation by streptococcal antigen (SA) when compared with those from healthy individuals. Strikingly, this enhanced proliferation of PBMCs was attenuated after administration of SA treated with DNase-I. In addition, CD69 expression levels on T cells, including skin-homing lymphocyte cutaneous lymphocyte-associated antigen positive T cells, and IFN-alpha secretion by PBMCs were also attenuated in patients after stimulation with SA without nucleic acid (non-nucleic acid SA, non-NASA) compared with stimulation with untreated SA. However, activation marker CD86 expression levels on B cells as well as the secretion of IFN-gamma and tumor necrosis factor (TNF)-alpha following stimulation with SA or non-NASA were not significantly altered. Interestingly, the attenuated T-cell activation and IFN-alpha secretion in psoriatic patients could be reconstituted when stimulated by non-NASA combined with synthetic CpG-A, but not when combined with synthetic CpG-B. This study demonstrates the integral function of SA, particularly streptococcal DNA, in the pathogenesis of psoriasis.

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.

Establishment of the Mouse Model by Rabbit Antiserum Specific to EC1-2 or EC3-4 Epitopes for Studying the Pathogenesis of Pemphigus Vulgaris

The research goal was to establish the neonatal mouse model by specific rabbit anti EC1-2 or EC3-4 antiserum for the purpose of studying pemphigus vulgaris (PV) pathogenesis. RNA was extracted from human keratinocytes. The cDNAs was synthesized by reverse transcription. Amplified EC1-2 or EC3-4 genes were inserted into pGEX-4T expression plasmids to constitute the recombinant plasmids, and transformed into E.coli. for the expression of the fusion proteins. The purified fusion proteins were used to immunize New Zealand white rabbits to obtain the specific anti EC1-2 or EC3-4 antisera. IgG fractions from the antisera were purified and passively transferred intradermally into the upper back skin of neonatal BALB/c mice. Histologic, ultrastructural, and immunofluorescence features of PV were evaluated in these mice. PV features were shown in the mice injected with anti EC1-2 antibody, erythema on the flanks and positive Nikolsky sign. The histology showed intraepidermal vesicle formation and acantholytic cells within. Acantholysis, but no clinical symptoms, was seen in the mice treated with the antibody specific to EC3-4. Additionally, skin sections from the abdomen from these neonatal mice were cryo-sectioned for direct-immunofluorescence. FITC-conjugated IgG antibody deposit between the keratinocytes throughout the epidermis. The indirect immunofluorescence with monkey esophagus showed the presence of anti-intracellular antibody with a titer of 1:40. On electronic microscopy, intercellular spaces (ICS) were widened and the desmosomes were split or dissolved. A novel PV mouse model was established by treatment with the specific rabbit antiserum. These data confirmed that both EC1-2 and EC3-4 are pathogenic epitopes in PVA, but EC1-2 is more dominant.

Novel heterozygous mutation of protoporphyrinogen oxidase gene in a Chinese patient with variegate porphyria

Dear Editor, Porphyrias are a group of rare diseases caused by the abnormal functioning of enzymes involved. For example, it was known that X-linked protoporphyria is caused by a gain of function mutation in ALAS2. Variegate porphyria (VP) is caused by decreased activity in the seventh enzyme protoporphyrinogen oxidase (PPOX). Here, we report a novel PPOX mutation in a VP patient who suffered from an unusual liver dysfunction. A 16-year-old male adolescent had a 2-year summer seasonal history of skin photosensitivity and fragility at sun-exposed areas (Fig. 1a–c). Histopathology with hematoxylin–eosin showed subepidermal bullae (Fig. 1d). Coproporphyrin in both urine and feces were strongly positive. The plasma fluorescence emission peak was detected at 628 nm which favored the diagnosis of VP. Following this diagnosis, he was advised to avoid inducing factors such as exposure to sunlight, metabolic stress, alcohol and sulfonamides (full list in www.porphyria-eur ope.com) and prescribed medication (fusidic acid and physical sunscreen). The lesions subsided quickly. Nine months later, he revisited us due to strong abdominal pain, vomiting and constipation without tenderness or other peritoneal signs. The porphobilinogen qualitative determination of urine was strongly positive. The routing biochemical indices were also examined. They were within normal range except the liver panel and

Modulation of desmoglein-3-specific T cell response and pathogenic antibody generation in mice

Pemphigus is a severe blistering disease of the skin and mucous membranes caused by pathogenic autoantibodies to desmosomal adhesion proteins desmoglein-3 (Dsg3) and desmoglein-1 (Dsg1). The antibody titer and the distinct isotype patterns correlated with the disease activity. To identify their functional properties and pathogenic potential, we immunized C57BL/6 and Balb/c mice with recombinant Dsg3 fusion protein plus complete Freunds adjuvant (CFA) or Aluminum Hydroxide hydrate (Alum). After immunization, the cytokine profiles on T cells, the antibody titers, and the isotypes were analyzed. The pathogenicity of different autoantibody isotypes was evaluated by antibody passive transfer approach. It was found that Th1 type cytokine interferon gamma (IFN gamma) was elevated in the CFA-treated group, while Th2 type cytokine interleukin-4 (IL-4) was increased in the Alum-treated group. IgG1 expression was persistent in the Alum group while IgG2a was predominant in the CFA group. Neonatal mice transferred with sera from the Alum group, but not the CFA group, developed skin lesions clinically and histologically with IgG deposition on the epidermal keratinocytes. Our findings suggest that distinct T cell responses could be switched after active immunization combined with different adjuvants, resulting in distinct anti-Dsg3 antibody isotypes with different pathogenic activities in disease development. These findings shed new light on the immunopathogenesis of PV and offer a new therapeutic strategy for this potentially fatal disorder.

Normal human skin is superior to monkey esophagus substrate for detection of circulating BP180-NC16A-specific immunoglobulin G antibodies in bullous pemphigoid

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering skin disease. Two antigens have been identified as targets of circulating autoantibodies (autoAbs) – BP180 and BP230 – with BP180 being a critical transmembrane adhesion protein of basal keratinocytes of the epidermis. The noncollagenous domain 16A (NC16A) of BP180 is the immunodominant epitope in patients with BP, and anti‐BP180‐NC16A IgG antibodies (Abs) correlate to disease activity. Routine serological testing and follow‐up of BP relies on indirect immunofluorescence (IIF) of serum Abs, commonly performed on monkey oesophagus (ME), and/or enzyme‐linked immunosorbent assay (ELISA) testing on recombinantly produced fragments of BP180 and BP230 (BP180‐NC16A, BP230‐C/N).

Endoscopic characteristics of oesophagus involvement in mucous membrane pemphigoid

allele frequencies > 15% as in this study, but future investigations testing rarer variants might uncover more risk loci to further delineate underlying oncogenic pathways in cSCC. Although this is a preliminary study, Wei et al. demonstrate that risk prediction models can be extended to incorporate a transplant patient’s genetic susceptibility to cSCC to better identify individuals at higher risk of early cSCC development post-transplant and tailor screening intensity. This personalized strategy could improve on and ultimately even replace risk stratification based on conventional phenotypic risk factors, which are currently used to guide dermatological screening and evaluations. Thus, augmenting risk-prediction models with genomic risks can pave the way for precision medicine, and provide new opportunities to translate genetic information to early clinical interventions and ultimately improve clinical outcomes.

Location of oral lesions predicts treatment resistance in pemphigus vulgaris

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