Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

Primary cutaneous CD 30 (+) ALK (-) anaplastic large cell lymphoma with dermoscopic findings: a case report

Primary cutaneous CD 30 (+) anaplastic large cell lymphoma (PCALCL) is a rare and indolent type of cutaneous T cell lymphoma, which usually presents as an asymptomatic solitary firm nodule that rapidly grows and often ulcerates without any systemic involvement. A 64-year-old female presented to our outpatient clinic with a one-year history of multiple pink nodular lesions on the chest, back and gluteal regions. Dermoscopic examination of the nodular lesions revealed pink-to-yellow structureless areas and arborizing-to-polymorphous vessels. Histopathologic examination was consistent with CD30 (+) anaplastic large cell lymphoma. Systemic involvement was not detected. Local radiotherapy for large nodules and surgical excision for small nodules were performed. The large nodules had totally regressed after 10 sessions of radiotherapy

An investigation of cytochrome p450 (CYP) and glutathione S-transferase (GST) isoenzyme protein expression and related interactions with phototherapy in patients with psoriasis vulgaris

Uzuncakmak, Tugba Kevser Ustunbas/0000-0001-8057-3463; Bozer, Busra/0000-0002-7280-4417WOS: 000393798500034PubMed: 27613512Oxidative stress may play an important role in the pathogenesis of psoriasis. Glutathione S-transferases (GSTs) make up a group of antioxidant enzymes. Cytochrome p450 (CYP) enzymes can influence oxidation and reduction reactions. We investigated the potential effects of GST and CYP enzymes in the pathogenesis of psoriasis. The study included 32 psoriasis patients and 22 healthy subjects. Psoriasis patients were administered 20 sessions of narrowband ultraviolet B phototherapy. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining. Expression levels of GSTK1, GSTM1, and GSTT1 were significantly higher in psoriasis than in control tissues (P = 0.022, P = 0.001, and P = 0.006, respectively). Pre- and post-treatment expression was similar. Expression of CYP1A1 and CYP2E1 was significantly higher in pre- (P = 0.003 and P = 0.001, respectively) and post-treatment (P = 0.003 and P = 0.001, respectively) psoriatic tissues than in control tissues. No significant differences in CYP1B1 levels between the study and control groups were detected before treatment (P > 0.05). However, CYP1B1 levels were higher in post-treatment psoriatic tissue than in control tissue (P = 0.045). The significant increases in expression of GSTK1, GSTM1, and GSTT1 in psoriasis may reflect the increased activation of GST in response to excessive free radical formation from activated neutrophils or ultraviolet exposure to maintain antioxidant capacity in psoriasis. Furthermore, expressions of CYP1A1 and CYP2E1 represent important enzymatic systems in psoriasis. These findings suggest that psoriasis is an oxidative stress condition, although phototherapy does not affect these enzymatic systems. Further investigation is required.Istanbul Medeniyet University Scientific Research Project [TTU-2013-431]This study was supported by Istanbul Medeniyet University Scientific Research Project 2013 (TTU-2013-431)

Systemic comorbidities associated with rosacea: a multicentric retrospective observational study

WOS: 000472185200024PubMed ID: 30575019BackgroundOnce considered a disorder limited to the skin, rosacea is now known to be associated with systemic disorders. The aim of this study was to determine what systemic comorbidities accompany rosacea and to determine the relationship between the type, severity, and duration of rosacea, and the presence of and type of systemic comorbidities. MethodsThis retrospective multicenter study was conducted by the Turkish Society of Dermatology Acne Study Group. Thirteen dermatology clinics throughout Turkey participated in the study. A structured physician-administered questionnaire was used to collect patient demographics, clinical findings, and lifestyle data. The principal rosacea subtype, physician global assessment of severity, and duration of rosacea were recorded. Physicians recorded each participant's medical history, including current and past comorbidities, duration of any such comorbidity, and the use of medications to treat any comorbidities. ResultsThe study included 1,195 rosacea patients and 621 controls without rosacea aged 18-85years. As compared to the controls, more of the rosacea patients had respiratory tract, gastrointestinal system, and metabolic and hepatobiliary system disorders in a rosacea's severity- and duration-dependent manner. ConclusionClinicians must be aware of the potential for systemic comorbidities in rosacea patients, which becomes more likely as disease duration and severity increase

Comparing the levels of CTLA-4-dependent biological defects in patients with LRBA deficiency and CTLA-4 insufficiency

Background Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency and cytotoxic T-lymphocyte protein-4 (CTLA-4) insufficiency are recently described disorders that present with susceptibility to infections, autoimmunity, and lymphoproliferation. Clinical and immunological comparisons of the diseases with long-term follow-up have not been previously reported. We sought to compare the clinical and laboratory manifestations of both diseases and investigate the role of flow cytometry in predicting the genetic defect in patients with LRBA deficiency and CTLA-4 insufficiency. Methods Patients were evaluated clinically with laboratory assessments for lymphocyte subsets, T follicular helper cells (T-FH), LRBA expression, and expression of CD25, FOXP3, and CTLA4 in regulatory T cells (Tregs) at baseline and 16 h post-stimulation. Results LRBA-deficient patients (n = 29) showed significantly early age of symptom onset, higher rates of pneumonia, autoimmunity, chronic diarrhea, and failure to thrive compared to CTLA-4 insufficiency (n = 12). In total, 29 patients received abatacept with favorable responses and the overall survival probability was not different between transplanted versus non-transplanted patients in LRBA deficiency. Meanwhile, higher probability of survival was observed in CTLA-4-insufficient patients (p = 0.04). The T-cell subsets showed more deviation to memory cells in CTLA-4-insufficiency, accompanied by low percentages of Treg and dysregulated cT(FH) cells response in both diseases. Cumulative numbers of autoimmunities positively correlated with cT(FH) frequencies. Baseline CTLA-4 expression was significantly diminished in LRBA deficiency and CTLA-4 insufficiency, but significant induction in CTLA-4 was observed after short-term T-cell stimulation in LRBA deficiency and controls, while this elevation was less in CTLA-4 insufficiency, allowing to differentiate this disease from LRBA deficiency with high sensitivity (87.5%) and specificity (90%). Conclusion This cohort provided detailed clinical and laboratory comparisons for LRBA deficiency and CTLA-4 insufficiency. The flow cytometric approach is useful in predicting the defective gene; thus, targeted sequencing can be conducted to provide rapid diagnosis and treatment for these diseases impacting the CTLA-4 pathway