Erkan Alpsoy

Cutting Edge: A Common Polymorphism Impairs Cell Surface Trafficking and Functional Responses of TLR1 but Protects against Leprosy

TLRs constitute an essential family of pattern recognition molecules that, through direct recognition of conserved microbial components, initiate inflammatory responses following infection. In this role, TLR1 enables host responses to a variety of bacteria, including pathogenic species of mycobacteria. In this study, we report that I602S, a common single nucleotide polymorphism within TLR1, is associated with aberrant trafficking of the receptor to the cell surface and diminished responses of blood monocytes to bacterial agonists. When expressed in heterologous systems, the TLR1 602S variant, but not the TLR1 602I variant, exhibits the expected deficiencies in trafficking and responsiveness. Among white Europeans, the 602S allele represents the most common single nucleotide polymorphism affecting TLR function identified to date. Surprisingly, the 602S allele is associated with a decreased incidence of leprosy, suggesting that Mycobacterium leprae subverts the TLR system as a mechanism of immune evasion.

Clinical features and natural course of Behçet’s disease in 661 cases: a multicentre study

Background  Behçet’s disease (BD) is a systemic inflammatory disease with unpredictable exacerbations and remissions. The natural course of BD is not fully known.

Cimetidine therapy for warts: a placebo-controlled, double-blind study.

BACKGROUND Cimetidine, an H2-receptor antagonist, has been used successfully to treat patients with mucocutaneous candidiasis, common variable immunodeficiency, herpes simplex, and herpes zoster because of its immunomodulatory effects. Recently, some trials have suggested that cimetidine may also be useful for the treatment of warts. OBJECTIVE The aim of the present study was to determine whether cimetidine is effective in the treatment of warts. METHODS Seventy patients with multiple warts were included in a placebo-controlled, double-blind study. Patients were randomly allocated to treatment groups equally. The groups received cimetidine, 25 to 40 mg/kg daily, or placebo for 3 months. Patients were examined at monthly intervals. RESULTS At the end of the therapy, 28 cimetidine-treated and 26 placebo-treated patients were examined to determine the efficacy of treatment. Cure rates obtained were 32% (9 of 28) in the cimetidine-treated group and 30.7% (8 of 26) in the placebo-treated group. No significant difference was found between cimetidine and placebo in effectiveness (p = 0.85). CONCLUSION Our results show that cimetidine is no more effective than placebo in the treatment of patients with common warts.

Identification of multiple independent susceptibility loci in the HLA region in Behçet's disease

Behçets disease is an inflammatory disease characterized by recurrent oral and genital ulcers and significant organ involvement. Localizing the genetic association between HLA-B*51 and Behçets disease and exploring additional susceptibility loci in the human leukocyte antigen (HLA) region are complicated by the strong linkage disequilibrium in this region. We genotyped 8,572 variants in the extended HLA locus and carried out imputation and meta-analysis of 24,834 variants in 2 independent Behçets disease cohorts from 2 ancestry groups. Genotyped SNPs were used to infer classical HLA alleles in the HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1 and HLA-DRB1 loci. Our data suggest that the robust HLA-B*51 association in Behçets disease is explained by a variant located between the HLA-B and MICA genes (rs116799036: odds ratio (OR) = 3.88, P = 9.42 × 10−50). Three additional independent genetic associations within PSORS1C1 (rs12525170: OR = 3.01, P = 3.01 × 10−26), upstream of HLA-F-AS1 (rs114854070: OR = 1.95, P = 7.84 × 10−14) and with HLA-Cw*1602 (OR = 5.38, P = 6.07 × 10−18) were also identified and replicated.

Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo-controlled double-blind study

Background  Encouraging results of previous uncontrolled trials suggest that calcipotriol may potentiate the efficacy of psoralen plus ultraviolet (UV) A (PUVA) therapy in patients with vitiligo.

TNF-α gene 1031 T/C polymorphism in Turkish patients with Behçet's disease

Background  Genetic factors that predispose individuals to Behçets disease (BD) are considered to play an important role in development of the disease. The tumour necrosis factor (TNF)‐α gene, which is closely linked to the HLA‐B51 gene, is involved in susceptibility for BD. Recently, a polymorphism at position −1031 within the TNF‐α promoter region was demonstrated to be responsible for susceptibility to BD in a British population. However, the functional effects of this polymorphism have not yet been determined.

Specific interleukin‐1 gene polymorphisms in Turkish patients with Behçet's disease

Abstract:  Genetic factors that predispose individuals to Behçets disease (BD) are considered to play important roles in the development of the disease. The pro‐inflammatory cytokine interleukin‐1 (IL‐1) has been implicated in the pathogenesis of BD. Our aim was to determine a possible association of specific polymorphisms of IL‐1α, IL‐1β, and IL‐1 receptor antagonist genes with susceptibility for BD. We genotyped 72 patients with BD and 163 healthy controls for IL‐1α−889, IL‐1β−511, and +3953 (nt5887) single‐nucleotide polymorphisms besides IL‐1 receptor antagonist variable number of tandem repeat polymorphism (for five different alleles). Comparison of the IL‐1β+3953 T allele and TT genotype frequencies showed a significant difference between patients with BD and controls (54.2 vs. 40.5%, OR = 1.74, P = 0.024, and 40.3 vs. 19.6%, OR = 2.76, P = 0.009, respectively). However, no difference was observed in the genotype or allele frequencies of IL‐1α−889, IL‐1β−511, and IL‐1 receptor antagonist between the patients with BD and the controls. Our results indicate that susceptibility to BD is increased in individuals carrying the IL‐1β+3953 T allele and TT genotype.

Intermittent Therapy with Terbinafine for Dermatophyte Toe‐Onychomycosis: A New Approach

Terbinafine, an orally active antifungal agent of the allylamine class, is effective in the treatment of dermatophyte onycomycosis. Its pharmacologic and pharmacokinetic properties give strong support to the possibility that intermittent treatment courses may be equally effective in onychomycosis in general.

The clinical course of Behçet's disease in pregnacy: A retrospective analysis and review of the literature

Although Behçets disease is mainly diagnosed during the reproductive periods of life, we know little about the influence of pregnancy on the clinical course of Behçets disease. Therefore, we analyzed the relationship between Behçets disease and pregnancy retrospectively, in order to detect any possible interaction between the two multisystemic processes, particularly in regard to the influence of pregnancy on the clinical course of Behçets disease. We studied 44 pregnancies in 28 women with Behçets disease. The diagnoses were made according to the criteria of the International Study Group for Behçets disease. The patients were observed during pregnancy and puerperium periods at monthly intervals. The existence and incidence of symptoms were recorded during these periods. There was remission of Behçets disease during 23 (52.3%) pregnancies, although the disease had been in a stage of exacerbation before pregnancy. The disease became exacerbated during 12 (27.3%) pregnancies, although it had been in a stage of remission before pregnancy. There were no changes in the clinical course of Behçets disease in 9 (20.4%) pregnancies. The most frequent manifestations of the clinical exacerbation were increases in the intensity and severity of outbreaks of oral ulcers during pregnancy. Outbreaks of genital ulcers, eye inflammations, and arthritis were other signs of exacerbation. Other than spontaneous abortion in three patients, we did not observe maternal or fetal complications. Although Behçets disease tends toward remission during pregnancy, the influence of pregnancy on its clinical course is quite variable between patients and even during different pregnancies in the same patient. On the basis of our and previous results, we speculate that pregnancy in general does not seem to markedly affect the natural course of Behçets disease.

Interferon therapy for Behçet's disease

BACKGROUND Behçets disease was first described in 1937 as a trisymptom complex. No standard therapy has been established. Its cause is presumed to be viral or immunologic. OBJECTIVE We sought to determine whether patients with Behçets disease benefit from interferon, which has antiviral, immunomodulatory, antiproliferative, and antitumoral properties. METHODS Fourteen patients were initially given 3 MU interferon alfa-2a subcutaneously three times per week. The doses were gradually increased to 12 MU. Each patient received a total dose of 216 MU during the 2-month study. Therapy with 9 MU interferon alfa-2a once a month was continued in half the patients. All patients were observed before and after treatment for 6-month periods, and all symptoms were recorded. RESULTS All patients were symptom free by the end of the 2-month treatment period. The frequencies of oral and genital ulcers as well as pustular vasculitis decreased significantly in the posttreatment period as compared with the pretreatment period. CONCLUSION The data suggest that interferon treatment appears to be effective for patients with Behçets disease.