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4 ! "N* CVID!. $ IL-17 UL! ) NB </ >< $ ]B $-.$N $R # y8b >< <B 'RB 7 $! $ CVID! =N! $ IL-17 $ $.! +<! $.! $ 12 ) + "-D _! $$ 6, $ RB 7.(15) </ Y,D! =N!! * A $ CVID! =N! + IL-12 ), $,- Crohn ) $,- ) B+ </$ IFNγ $ `RB ).(16) <6 >< $ IL-23 + IL-17 $ ><# "$!! ] 'IL-17! }N3! $ IL-17 <^.</! si!! <3 - ) $N $R # a.</! RB ) $! $<R3 $! ] 4B$ CVID! =N! $ IL-17 ;! $N ><$ 6 '</ $-! * A $ %& $ $ + TH17 12 ) + "! "(!! $ [ %& + ) ) 2B$ s.</! $- ) $ 1 j(c 5/,& M2 >6$ 6+x& "+R + <-D ><j! +x& ) B N6& )J + </$ +x& )! 5 1 ><56$ ;B >+D 4& `I, + 563, >6 # + 5/,&.] +- 'Q_+ $ + -,! $!# /3! + H, $ B "(B, 3 '$S+ )!." 8 +(B "-! Tumor necrosis ) TACI ^ 15B $ '(factor receptor superfamily member 13B '(Inducible costimulatory molecule) ICOS BAFF-R 'CD81 'CD19 'CD21 ' $ ; <^ + (B cell-activating factor receptor) A 4=&! B 12, 3 + A! $ -D a $! ) BI "2 '<$.(14-15) $/ p3 6! " IL B+ n$/ <B3 TH17 12 NK J $ 4& IL-17.< <B3 IL-17, (Natural killer) 12 +!!* j?n3!jb,s >x +! '3v ]* + T ) ')J.< _! '3v %& <B ,- [S ).(14) $/ )*( $ <!+5<s $ BAFF ) +$ '1! }N3 $ + TACI >< q& +$ 1R-! $_ APRIL + <* (B-Cell maturation antigen) BCMA A #, 3 + B 12 1R- & 4I $ < ><! M& 1 BAFF A.(14) <$ BAFF >< q& l? B 12 ~2! + p3 APRIL + BAFF,.(4) </! IL-17 a!jb ><!& ).(12) <!,- ) ;! 'si +x& $ 361

5 References 1. Kopecky O, Lukesova S. Genetic defects in common variable immunodeficiency. Int J Immunogenet 2007; 34(4): Pourpak Z, Aghamohammadi A, Etemad Saeid S, Heidarzadeh M, Sedighipour L. Relative frequency humoral primary immunodeficiency in identical patients with CVID in CVID patients. Tehran Univ Med J 2005; 63(5): Olerup O, Smith CI, Bjorkander J, Hammarstrom L. Shared HLA class II-associated genetic susceptibility and resistance, related to the HLA- DQB1 gene, in IgA deficiency and common variable immunodeficiency. Proc Natl Acad Sci U S A 1992; 89(22): Bacchelli C, Buckridge S, Thrasher AJ, Gaspar HB. Translational mini-review series on immunodeficiency: molecular defects in common variable immunodeficiency. Clin Exp Immunol 2007; 149(3): Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan- American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol 1999; 93(3): Holm AM, Aukrust P, Damas JK, Muller F, Halvorsen B, Froland SS. Abnormal interleukin-7 function in common variable immunodeficiency. Blood 2005; 105(7): Holm AM, Aukrust P, Aandahl EM, Muller F, Tasken K, Froland SS. Impaired secretion of IL-10 by T cells from patients with common variable immunodeficiency--involvement of protein kinase A type I. J Immunol 2003; 170(11): Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17- producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 2005; 6(11): Vorechovsky I, Webster AD, Plebani A, Hammarstrom L. Genetic linkage of IgA deficiency to the major histocompatibility complex: evidence for allele segregation distortion, parent-of-origin penetrance differences, and the role of anti-iga antibodies in disease predisposition. Am J Hum Genet 1999; 64(4): Mechanic LJ, Dikman S, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Ann Intern Med 1997; 127(8 Pt 1): Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD, et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 2007; 8(9): Doreau A, Belot A, Bastid J, Riche B, Trescol- Biemont MC, Ranchin B, et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol 2009; 10(7): Rezaei N, Aghamohammadi A, Notarangelo LD. Primary immunodeficiency diseases: Definition, diagnosis, and management. Berlin, Germany: Springer; Abbas AK, Lichtman AHH, Pillai Sh. Cellular and molecular immunology. 7 th ed. Philadelphia, PA: Saunders; Barbosa RR, Silva SP, Silva SL, Melo AC, Pedro E, Barbosa MP, et al. Primary B-cell deficiencies reveal a link between human IL-17-producing CD4 T-cell homeostasis and B-cell differentiation. PLoS One 2011; 6(8): e Mannon PJ, Fuss IJ, Dill S, Friend J, Groden C, Hornung R, et al. Excess IL-12 but not IL-23 accompanies the inflammatory bowel disease associated with common variable immunodeficiency. Gastroenterology 2006; 131(3):

6 Journal of Isfahan Medical School Received: Vol. 31, No. 230, 4 th Week, May 2013 Accepted: Evaluation of IL-17 Gene Expression in the Peripheral Blood of Patients with Common Variable Immunodeficiency Reza Yazdani 1, Mazdak Ganjalikhani Hakemi PhD 2, Roya Sherkat MD 3, Mohsen Masjedi PhD 2, Hamid Zarkesh PhD 4, Mohsen Hosseini PhD 5 Abstract Original Article Background: Producing IL-17, Th17 cells induce BAFF and APRIL, two important mediators for B- cell survival and activation. Common variable immunodeficiency (CVID) is a group of many primary immunodeficiency diseases with a common set of features (including hypo-gammaglobulinemia) and different underlying causes. The prevalence of CVID is 1 to 50,000. Hence, the aim of this study was to measure IL-17 gene expression in peripheral blood of patients with CVID. Methods: Total mrna extracted from whole blood samples of 10 patients with CVID and 10 normal controls; then, IL-17 gene was measured using qrt-pcr. Findings: There was a slight decrease in transcript levels of IL-17 in patients with CVID, even though, it was not statistically significant (P = 0.195). Conclusion: We showed that IL-17 is decreased in patients with CVID and this could be an explanation for their humoral immunity response insufficiencies. Absence of statistical significance in this IL-17 reduction may be due to our sample size and increasing the number of samples may result in statistical significance of this in future studies. Keywords: Common variable immunodeficiency, Cytokin, IL-17, Th17, Real time-pcr Citation: Yazdani R, Ganjalikhani Hakemi M, Sherkat R, Masjedi M, Zarkesh H, Hosseini M. Evaluation of IL-17 Gene Expression in the Peripheral Blood of Patients with Common Variable Immunodeficiency. J Isfahan Med Sch 2013; 31(230): * This paper is derived from a MSc thesis No in Isfahan University of Medical Sciences. 1- MSc Student, Department of Immunology, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran 2- Assistant Professor, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 3- Associate Professor, Infectious Diseases and Tropical Medicine Research Center AND Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran 4- Associate Professor, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 5- Associate Professor, Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran Corresponding Author: Roya Sherkat MD, sherkat@med.mui.ac.ir 363

( )* CVID) (Common variable immunodeficiency. IgM (Immunoglobulin A) IgA (Immunoglobulin G) $ $%&' $%&' ()* +

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