Xiaoqing Zhao

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.

The imbalance of Th17 and regulatory T cells in pemphigus patients

UNLABELLED 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. OBJECTIVES 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). METHODS 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. RESULTS 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. CONCLUSION 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.

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

Pemphigus is an organ‐specific autoimmune bullous disease.

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.

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.

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.

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.

Recurrent fungal infections in a Chinese patient with CARD9 deficiency and a review of 48 cases

Deficiency of CARD9 (caspase recruitment domain‐containing protein 9) has been reported in individuals with recurrent and invasive fungal infections. We report on a patient who first had Trichosporon asahii affecting the skin then Candida albicans infections involving the digestive tract and knee joint, along with elevated serum IgE. After stimulation with C. albicans, peripheral blood mononuclear cells of this patient produced less tumour necrosis factor‐α, interferon‐γ and interleukin‐17 than those of healthy controls. Furthermore, the serum IgE levels of this patient were positively correlated with the severity of fungal infection during the course of treatment. Sanger sequencing identified one homozygous frameshift mutation (p.D274fsX60) in CARD9. We further performed a review including 48 cases with CARD9 deficiency. According to the data published previously, CARD9‐deficient patients demonstrated obviously elevated IgE in serum (median 1300 IU mL−1), which could distinguish them from otherwise healthy people with fungal infections (area under the curve 0·94, P < 0·001). Patients carrying the mutations Q289X and Q295X had a higher mortality rate (24% vs. 0%, P < 0·05). Patients with the mutations R18W, R35Q, R70W, G72S or Y91H in the CARD domain, and the nonsense mutation Q295X in the coiled‐coil domain, seemed to be more prone to Candida infections (90% vs. 20%, P < 0·005) and central nervous system infections (60% vs. 12%, P < 0·005).

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

False‐positive intercellular indirect immunofluorescence test due to anti‐blood group antibodies in a patient with epidermolysis bullosa acquisita

We report a case of an epidermolysis bullosa acquisita (EBA) patient with a unique immunofluorescence pattern. The patient had pruritic erythematous plaques and tense blisters. Histopathological examination showed a subepidermal blister without acantholysis. Salt‐split direct immunofluorescence demonstrated clear linear IgG and C3 deposition along the dermal side of the basement membrane zone; this deposition is characteristic of EBA. Indirect immunofluorescence (IIF) using monkey esophagus mucosa as substrate showed intercellular IgG deposition throughout the epidermis, which suggested pemphigus. After absorption with erythrocytes of blood group AB, the patient’s serum showed no deposition in IIF. We reviewed the literatures regarding false‐positive intraepidermal immunofluorescence staining due to cross‐reactivity of ABO blood group antibodies and suggest that this possibility should be considered in cases with conflicting immunofluorescence patterns.