F. Hao

Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.

Mutations in POFUT1, encoding protein O-fucosyltransferase 1, cause generalized Dowling-Degos disease.

Dowling-Degos disease (DDD), or reticular pigmented anomaly of the flexures, is a type of rare autosomal-dominant genodermatosis characterized by reticular hyperpigmentation and hypopigmentation of the flexures, such as the neck, axilla, and areas below the breasts and groin, and shows considerable heterogeneity. Loss-of-function mutations of keratin 5 (KRT5) have been identified in DDD individuals. In this study, we collected DNA samples from a large Chinese family affected by generalized DDD and found no mutation of KRT5. We performed a genome-wide linkage analysis of this family and mapped generalized DDD to a region between rs1293713 and rs244123 on chromosome 20 [corrected]. By exome sequencing, we identified nonsense mutation c.430G>T (p.Glu144(∗)) in POFUT1, which encodes protein O-fucosyltransferase 1, in the family. Study of an additional generalized DDD individual revealed the heterozygous deletion mutation c.482delA (p.Lys161Serfs(∗)42) in POFUT1. Knockdown of POFUT1 reduces the expression of NOTCH1, NOTCH2, HES1, and KRT5 in HaCaT cells. Using zebrafish, we showed that pofut1 is expressed in the skin and other organs. Morpholino knockdown of pofut1 in zebrafish produced a phenotype characteristic of hypopigmentation at 48 hr postfertilization (hpf) and abnormal melanin distribution at 72 hpf, replicating the clinical phenotype observed in our DDD individuals. At 48 and 72 hpf, tyrosinase activities decreased by 33% and 45%, respectively, and melanin protein contents decreased by 20% and 25%, respectively. Our findings demonstrate that POFUT1 mutations cause generalized DDD. These results strongly suggest that the protein product of POFUT1 plays a significant and conserved role in melanin synthesis and transport.

Chronic urticaria in Chinese population: a hospital-based multicenter epidemiological study.

The epidemiologic profiles of chronic urticaria (CU) vary considerably among regions, and few such data are available from China.

Increased circulating follicular helper T cells and activated B cells correlate with disease severity in patients with psoriasis

Follicular Helper T (TFH) Cells are a population of recently discovered CD4+ T cells involved in autoimmune diseases. However, the contribution of TFH cells in patients with psoriasis remains unknown.

Efficacy and safety of adalimumab in Chinese patients with moderate-to-severe plaque psoriasis: results from a phase 3, randomized, placebo-controlled, double-blind study

This phase 3 trial is the first to evaluate the efficacy and safety of treatment with the systemic TNF‐α inhibitor, adalimumab, for Chinese patients with moderate‐to‐severe plaque psoriasis.

Toll‐like receptor 2 agonist Pam3CSK4 up‐regulates FcεRI receptor expression on monocytes from patients with severe extrinsic atopic dermatitis

Both microbial antigens and allergens are important factors that can trigger atopic dermatitis (AD). Monocytes from patients with AD have been found to express increased and sustained levels of high‐affinity IgE receptor (FcεRI) and Toll‐like receptor 2 (TLR2). We hypothesized that putative interactions exist between TLR2 and FcεRI on monocytes in the pathogenesis of AD.

Basophil CD63 expression in chronic spontaneous urticaria: correlation with allergic sensitization, serum autoreactivity and basophil reactivity

The underlying causes and factors contributing to the disease severity of chronic spontaneous urticaria (CSU) are unknown.

A child case of hyper-IgE syndrome.

Hyper-IgE syndrome (HIES) is a rare and complex primary immunodeficiency disorder characterized by recurrent staphylococcal infection of the skin and lung, chronic eczema/atopic dermatitis, defective granulocyte chemotaxis and markedly high serum IgE level (1–3). We report the case of a 10-year-old girl with generalized molluscum contagiosum, oral candidiasis and pneumonia. She suffered from multiple episodes of generalized papules and pruritic eczematous lesions, recurrent infections since her early childhood. Physical examination showed numerous sessile, dome-shaped, umbilicated, flesh-colored to dull red and mildly tender nodules on her scalp, face, trunk and perinaeum, gluteal areas, varying in size from 5 mm to more than 2 cm (Fig. 1). Craniofacial features included a broad nasal bridge, bulky nasal tip and rough facial skin. Intra-oral examination revealed 10 deciduous teeth, gingival hypertrophy, irregular and carious teeth. Mycotic infections of nails are apparent. Marked growth retardation (height 120 cm, weight 22 kg) was noticed. There was no evidence of scoliosis or hyperextensibility of joints. Serum IgE levels were determined by using UniCAP/Pharmacia CAP System (Fully automated UniCAP(r) 100E Instrument. Phadia AB, Sweden.). Results showed the total serum IgE level was 5000 IU/ml (normal value 0–100 IU/ ml), but Phadiatop and fx5E were negative. Complete blood count yielded a white blood cell count of 10.34/ml with 73% of granulocytes, 5.4% of eosinophils. Although levels of immunoglobulins A and G were normal, the immunoglobulin M level was slightly low, at 0.535 g/l (normal, 0.63–2.77 g/l). Levels of CD3 was low at 55.1% and CD8 was low at 19.3% (normal, 20–35 g/l); CD4 and CD4/CD8 were within the normal range. Serum anti-HIV antibody detected by enzyme-linked immunosorbent assay was negative. Pathologic periodontal changes presented as inflammatory granuloma. Diagnosis of molluscum contagiosum was confirmed by pathohistology of her skin lesion. Chest radiographs showed pneumonia. Candida albicans was identified from culture of pseudomembranousc plaques in her oral cavity and finger nail. Dual-energy X-ray absorptiometry of the lumbar spine (L1-4) showed low bone mineral density (BMD 756 mg/cm; T-3.0, Z-1.3) which tells us she also had osteoporosis. Because a tendency toward osteoporosis and increased risk of spontaneous fractures has been reported (4), we measured bone density although the patients did not have a history of fractures. Markedly low bone density in relation to bone area (BMDa) has been found. We did not find hyperextensibility of joints or scoliosis, which have been found among as many as 68% and 76% of patients with hyper-IgE syndrome. Poor oral hygene, gingivitis, retention of teeth and prolonged exfoliation of deciduous teeth were detected in oral examination of this patient. We also confirmed the presence of typical facial features, such as a prominent forehead and broad nasal bridge in our patient. HIES has been classified into type 1 and type based on clinical and Hyper-IgE syndrome is not only an immunodeficiency but also is a multisystem disorder. ALLERGY Net

Different expression patterns of plasma Th1‐, Th2‐, Th17‐ and Th22‐related cytokines correlate with serum autoreactivity and allergen sensitivity in chronic spontaneous urticaria

Clinical features and basophil activation levels correlate with serum autoreactivity and allergen sensitivity in patients with chronic spontaneous urticaria (CSU).

Dissection of a circulating CD3+CD20+ T cell subpopulation in patients with psoriasis: CD3+CD20+ T cells in psoriasis

CD3+CD20+ T cells are a population of CD3+ T cells that express CD20 and identified in healthy donors and autoimmune diseases. However, the nature and role of these cells in patients with psoriasis remain unclear. In this study, we aimed to investigate the level, phenotype, functional and clinical relevance of CD3+CD20+ T cells in the peripheral blood of patients with psoriasis. We found that a small subset of CD3+ T cells expressed CD20 molecule in the peripheral blood of patients with psoriasis, and their levels were similar to those in healthy donors. Circulating CD3+CD20+ T cells in patients with psoriasis were enriched in CD4+ cells and displayed an activated effector phenotype, as these cells contained fewer CD45RA+‐naive and CCR7+ cells with increased activity than those of CD3+ T cells lacking CD20. In addition, compared with healthy donors, circulating CD3+CD20+ T cells in patients with psoriasis produced more cytokines, interleukin (IL)‐17A, tumour necrosis factor (TNF)‐α and IL‐21, but not IL‐4 and IFN‐γ. Furthermore, a significantly positive correlation was found between the levels of IL‐17A, TNF‐α and IL‐21‐production CD3+CD20+ T cells with Psoriasis Area and Severity Index scores. Our findings suggest that CD3+CD20+ T cells may play a role in the pathogenesis of psoriasis.