HLA-B*1502 in Iranian Children with Anticonvulsant Drugs-Induced Skin Reactions

How to Cite This Article: Tonekaboni SH, Jafari N, Mansouri M, Jabbehdari S, Eftekhari R, Chavoshzadeh Z, Abdollah Gorji F, Mesdaghi M. HLA-B*1502 in Iranian Children with Anticonvulsant Drugs-Induced Skin Reactions. Iran J Child Neurol. Spring 2017; 11(2):26-30. AbstractObjectiveAnticonvulsant drugs can cause various forms of skin drug reactions, ranging from exanthema to severe blistering reactions. An association between HLA-B*1502 allele and severe skin reactions have been reported.Materials & Methods Fifteen patients with severe skin reactions following treatment with anticonvulsant drugs (Carbamazepine, lamotrigine, phenobarbital, primidone) and 15 controls (age-matched epileptic patients taking similar anticonvulsants without drug eruption) were included. They were referred to Mofid Children’s Hospital in Tehran, Iran, between Jan 2012 to Jan 2014. Genomic DNA was extracted from peripheral blood of all patients and HLA- B*1502 genotype was detected by real-time PCR.Results None of the patients was positive for HLA- B*1502, but two patients in control group had positive HLA- B*1502.Conclusion The HLA- B*1502 is not correlated with severe anticonvulsant drugs -induced skin reactions in Iranian children. References 1.Roujeau JC. Clinical heterogeneity of drug hypersensitivity. Toxicology 2005; 209: 123 –9.2.McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, Kasperavičiūtė D, Carrington M, et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 2011; 364(12):1134-43.3.Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe’er I, Floratos A, et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genetic 2009; 41:816–9.4.Amstutz U, Ross CJ, Castro-Pastrana LI, Rieder MJ, Shear NH, Hayden MR, Carleton BC. CPNDS Consortium; HLA-A 31:01 and HLA-B 15:02 as genetic markers for carbamazepine hypersensitivity in children. Clin Pharmacol Ther 2013; 94(1):142-9.5.Man CB, Kwan P, Baum L, Yu E, Lau KM, Cheng AS, Ng MH. Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia 2007; 48(5):1015-8.6.Zeng T, Long YS, Min FL, Liao WP, Shi YW. Association of HLA-B*1502 allele with lamotrigine-induced Stevens– Johnson syndrome and toxic epidermal necrolysis in Han Chinese subjects: a meta-analysis. Int J Dermatol 2015; 54(4):488-93.7.Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol 1993; 129(1):92-6.8. Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, Lee WR, et al. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics 2006; 16(4):297-306.9. Wang Q, Zhou JQ, Zhou LM, Chen ZY, Fang ZY, Chen SD, et al. Association between HLA-B*1502 allele and carbamazepine-induced severe cutaneous adverse reactions in Han people of southern China mainlan. Seizure 2011; 20 (6):446-8.10. Li LJ, Hu FY, Wu XT, An DM, Yan B, Zhou D. Predictive markers for carbamazepine and lamotrigine-induced maculopapular exanthema in Han Chinese. Epilepsy Res 2013; 106 (1-2):296-300.11. Kim SH, Lee KW, Song WJ, Kim SH, Jee YK, Lee SM, et al; Adverse Drug Reaction Research Group in Korea. Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans. Epilepsy Res 2011; 97 (1-2):190-7.12. Criado PR, Criado RFJ, Avancini JM, Santi CG. Drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS): a review of current concepts. An Bras Dermatol 2012; 87(3):435–49.13. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, et al. Medical genetics: a marker for Stevens– Johnson syndrome. Nature 2004; 428: 486.14. Man CB, Kwan P, Baum L, Yu E, Lau KM, Cheng AS, Ng MH. Association between HLA-B*1502 allele and antiepileptic drug induced cutaneous reactions in Han Chinese. Epilepsia 2007; 48: 1015–8.15. Locharernkul C, Loplumlert J, Limotai C, Korkij W, Desudchit T, Tongkobpetch S, et al. Carbamazepine and phenytoin induced Stevens–Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia 2008; 49:2087–91.16. Kaniwa N, Saito Y, Aihara M, Matsunaga K, Tohkin M, Kurose K, et al. HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens– Johnson syndrome and toxic epidermal necrolysis. Pharmacogenomics 2008; 9: 1617–22.17. Alfirevic A, Jorgensen AL, Williamson PR, Chadwick DW, Park BK, Pirmohamed M. HLA-B locus in Caucasian patients with carbamazepine hypersensitivity. Pharmacogenomics 2006; 7: 813–8.18. Tangamornsuksan W, Chaiyakunapruk N, Somkrua R, Lohitnavy M, Tassaneeyakul W. Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens- Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA Dermatol 2013; 149(9):1025-32

The frequency of HBeAg and relation with serum level of aminotransferase in chronic hepatitis B

زمینه و هدف: ویروس هپاتیت B (HBV) شایع ترین علت بیماری کبدی حاد و مزمن در جهان به شمار می رود. در افراد ناقل HBV می بایست وضعیت تکثیر ویروسی با استفاده از مارکرهای مناسب از جمله HbeAg مورد بررسی قرار گیرد تا در صورت مثبت بودن و همچنین بالا بودن آنزیم های کبدی افراد مبتلا به هپاتیت مزمن شناسایی شده و سپس تحت درمان قرار گیرند. لذا این مطالعه با هدف تعیین فراوانی مارکر HBeAg و ارتباط آن با سطح ترانس آمینازهای کبدی در افراد HBsAg مثبت انجام گرفت. روش بررسی: در این مطالعه توصیفی – تحلیلی 144 فرد آلوده به ویروس هپاتیت B در مراجعین به بیمارستان امام رضا(ع) شهر مشهد در سال 1385 انتخاب و سپس در سرم این افراد، HBeAg و آنزیم های کبدی با روش الایزا و تست های بیوشیمیایی اندازه گیری شدند. داده ها با استفاده از آزمون های آماری من ویتنی و کای دو تجزیه و تحلیل شد. یافته ها: فراوانی افراد 94 نفر مذکر و 50 نفر مونث بود. این افراد در محدوده سنی 85-2 با میانگین 3/2±4/37 سال قرار داشتند. 18 (26 نفر) دارای HBeAg در سرم بودند. میانگین آنزیم آسپارتات آمینو ترانسفراز (AST) در گروه HBeAg مثبت IU/L 83 و در گروه HBeAg منفی IU/L 2/56 بود (01/0

Study of the tumor microenvironment during breast cancer progression

Abstract Background Different cells and mediators in the tumor microenvironment play important roles in the progression of breast cancer. The aim of this study was to determine the composition of the microenvironment during tumor progression in order to discover new related biomarkers and potentials for targeted therapy. Methods In this study, breast cancer biopsies from four different stages, and control breast biopsies were collected. Then, the mRNA expression of several markers related to different CD4+ T cell subsets including regulatory T cells (Treg), T helper (Th) type 1, 2 and 17 were determined. In addition, we investigated the expression of two inflammatory cytokines (TNF-α and IL-6) and inflammatory mediators including FASL, IDO, SOCS1, VEGF, and CCR7. Results The results showed that the expression of Th1 and Th17 genes was decreased in tumor tissues compared to control tissues. In addition, we found that the gene expression related to these two cell subsets decreased during cancer progression. Moreover, the expression level of TNF-α increased with tumor progression. Conclusion We conclude that the expression of genes related to immune response and inflammation is different between tumor tissues and control tissues. In addition, this difference was perpetuated through the different stages of cancer