Z. Song

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.

Primary localized histoplasmosis with lesions restricted to the mouth in a Chinese HIV-negative patient

Histoplasmosis is a deep mycosis caused by Histoplasma capsulatum, which is endemic in many areas of the world but is relatively rare in China. Although the majority of cases present as a mild to moderate flu-like disease requiring only supportive therapy, approximately 1% of patients experience more serious pulmonary and extrapulmonary disease, which can be life-threatening if diagnosis is delayed or the treatment is not initiated rapidly. Definitive diagnosis is usually made by a combination of culture, detection of the organism in tissues, measurement of antibodies, and detection of antigen. We present the case of a 51-year-old patient who presented with histoplasmosis only, with several ulcerated lesions in the oral cavity and without HIV infection, who did not show any detectable signs and symptoms of systemic disease or extra-oral manifestations. Histopathological analysis indicated a chronic inflammatory process with granulomas with yeast-like organisms. Isolation of H. capsulatum and molecular identification provided the definitive diagnosis. Treatment with oral itraconazole led to remission of the oral lesions. This is the first Chinese case report of localized histoplasmosis with lesions restricted to the mouth in an HIV-negative patient.

Downregulation of TNIP1 Expression Leads to Increased Proliferation of Human Keratinocytes and Severer Psoriasis-Like Conditions in an Imiquimod-Induced Mouse Model of Dermatitis

Psoriasis is a chronic, inflammatory skin disease involving both environmental and genetic factors. According to genome-wide association studies (GWAS), the TNIP1 gene, which encodes the TNF-α–induced protein 3-interacting protein 1 (TNIP1), is strongly linked to the susceptibility of psoriasis. TNIP1 is a widely expressed ubiquitin sensor that binds to the ubiquitin-editing protein A20 and restricts TNF- and TLR-induced signals. In our study, TNIP1 expression decreased in specimens of epidermis affected by psoriasis. Based on previous studies suggesting a role for TNIP1 in modulating cancer cell growth, we investigated its role in keratinocyte proliferation, which is clearly abnormal in psoriasis. To mimic the downregulation or upregulation of TNIP1 in HaCaT cells and primary human keratinocytes (PHKs), we used a TNIP1 specific small interfering hairpin RNA (TNIP1 shRNA) lentiviral vector or a recombinant TNIP1 (rTNIP1) lentiviral vector, respectively. Blocking TNIP1 expression increased keratinocyte proliferation, while overexpression of TNIP1 decreased keratinocyte proliferation. Furthermore, we showed that TNIP1 signaling might involve extracellular signal-regulated kinase1/2 (Erk1/2) and CCAAT/enhancer-binding protein β (C/EBPβ) activity. Intradermal injection of TNIP1 shRNA in BALB/c mice led to exaggerated psoriatic conditions in imiquimod (IMQ)-induced psoriasis-like dermatitis. These findings indicate that TNIP1 has a protective role in psoriasis and therefore could be a promising therapeutic target.

Single-nucleotide Polymorphism and Haplotypes of TNIP1 Associated with Systemic Lupus Erythematosus in a Chinese Han Population

Objective. To determine the association of systemic lupus erythematosus (SLE) with single-nucleotide polymorphisms (SNP) in the TNIP1 gene and compare the expression of this gene in cases and controls from a Chinese Han population in this replication study. Methods. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to genotype 19 SNP in TNIP1 in Chinese Han patients with SLE (n = 341) and controls (n = 356). Genotypes were analyzed by codominant, dominant, and recessive models. Analysis of allele frequencies and linkage disequilibrium was also performed. Western blotting and qRT-PCR were used to measure the expression of these genes in peripheral blood mononuclear cells of SLE cases and controls. Results. Seven SNP loci were significantly associated with SLE in our population (p < 0.05 for all comparisons). Two TNIP1 gene haplotypes (ATTGCGC and GTCCTAT) were associated with SLE (p = 0.0246 and p = 0.0024, respectively). Western blotting and qRT-PCR results provide evidence that patients with SLE had significantly reduced expression of TNIP1/ABIN-1 relative to controls. Conclusion. Analysis of SNP in the TNIP1 gene and expression of this gene in peripheral blood lymphocytes indicated these SNP were associated with the occurrence of SLE in Han Chinese patients. Future studies should examine the roles of these SNP in the pathogenesis of SLE.

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.

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.

Four new cases of stiff skin syndrome with unusual presentations

Editor, Stiff skin syndrome (SSS) is a rare cutaneous connective tissue disorder which is highly heterogeneous and has distinct variants. Although SSS is characterized by stone-hard indurations and thickening of the skin and subcutaneous tissues and is accompanied by limited joint mobility and mild hypertrichosis, the phenotypes of SSS may be variable and sometimes unexpected. Herein we report four cases of SSS with unusual clinical presentations, including bilateral involvement, hernial sac-like changes, concomitant herpes zoster and low levels of immunoglobulins. The first case was a 20-year-old man who presented with a 17-year history of extensive muscle rigidity and limited joint mobility. Physical examination showed that the skin on the waist and joints of all four limbs was indurated and resistant to extension when pulled up in a pinch. On the lumbar area, there were brown plaques with clear boundaries. Hypertrichosis was noted

Symmetrical acral keratoderma revisited: proposal for a new term, ‘pigmented carpotarsal hyperkeratosis’

First reported from Taiwan mistakenly as acral acanthosis nigricans in 1991, pigmented carpotarsal hyperkeratosis or hyperkeratosis nigricans carpi et tarsi displays a peculiar distribution of velvety brown‐grey hyperpigmented plaques symmetrically on the flexural side of the wrists and ankles and on the dorsal sides of the hands and feet. A marked epidermal hyperkeratosis with typically mild acanthosis and papillomatosis is observed in histology. Whitish maceration upon perspiration or water exposure, with exacerbation in summer but remission in winter, is common. The association with obesity, endocrine disorders, atopic dermatitis, ichthyosis or malignancy is unknown. Familial occurrence and hereditary patterns are ill‐defined. There is preliminary evidence indicating a pathogenic role of missense mutation in the transcription factor 4 gene. Treatment is empirical, with good outcome with topical retinoids and keratolytic agents. Recurrence is common, and long‐term prognosis is unclear. To be distinguished are acral acanthosis nigricans, palmoplantar keratoderma of the Nagashima type, palmoplantar keratoderma of the Bothnian type and aquagenic palmoplantar keratoderma. Most reported cases are from Southern China and are predominantly observed in men between the ages of 20 and 40 years. The currently used term ‘symmetrical acral keratoderma’ is non‐specific and misleading and may lead to global unawareness, underreporting or misdiagnosis of this phenomenon. Further genetic and molecular studies are required to clarify its pathogenesis and relation to palmoplantar keratoderma.

Cutaneous tuberculosis in China – A multicentre retrospective study of cases diagnosed between 1957 and 2013

China has one of the largest populations with tuberculosis worldwide. Cutaneous tuberculosis (CTB) is a rare manifestation of mycobacterial infection. Although CTB is well described, it is important to periodically revisit the prevailing clinical and epidemiological features in most populated countries such as China, India, and Indonesia, where tuberculosis is still a major health problem.