Introduction Sarcoidosisisacomplexsystemicinflammatory disorder of unknown etiology characterized patho- logicallybynoncaseatinggranulomasthatcanman- ifest in virtually any organ system (1). Extra-pul- monarysarcoidosisrepresentsasignificantchallenge bothinitsdiagnosisandmanagement.Itmayalsobe amajorcauseofmorbidityandmortality,aswell(2). Racial and gender differences are reported in pa- tientswithextra-pulmonarysarcoidosisandtheclin- icalcourseisunpredictable(2-4). The exact immunopathogenesis of sarcoidosis still remains an enigma despite there has been tremendous evolution in the past decade. The hy- pothesis is that; some antigen(s) enter the host and are phagocytosed by antigen presenting cells Could HLA-DR B1*11 allele be a clue for predicting extra- pulmonary sarcoidosis? Ezgi Ozyilmaz 1 , Ozlem Goruroglu Ozturk 2 , Dilek Yunsel 1 , Ali Deniz 3 , Ismail Hanta 1 , Sedat Kuleci 1 , Gulsah Seydaoglu 4 , Eren Erken 5 , Ali Kocabas 1 1 Cukurova University Faculty of Medicine, Department of Pulmonary Disease, 01330, Adana,Turkey; 2 Cukurova University Faculty of Medicine,DepartmentofMedicalBiochemistry,01330,Adana,Turkey; 3 CukurovaUniversityFacultyofMedicine,DepartmentofCardi- ology, 01330, Adana,Turkey; 4 Cukurova University Faculty of Medicine, Department of Biostatistics, 01330, Adana,Turkey; 5 Cukurova UniversityFacultyofMedicine,DepartmentofRheumatologyandImmunology,01330,Adana,Turkey Abstract. Background: Several HLA-DR alleles have been described as a potential risk factor for sarcoidosis be- tween distinct ethnic groups however the relationship between HLA-DR alleles and extra-pulmonary sarcoidosis (EPS)isstillscarce. Objectives: Theaimofthisprospectivestudyistoinvestigatetherelationshipbetweenextra-pul- monaryinvolvementandHLA-DRgeneticanalysisinTurkishpatientswithsarcoidosis. Methods: Inthisstudy,we HLA-typedsarcoidosispatientswithandwithoutextra-pulmonaryinvolvement,andcomparedwithhealthycontrol subjects.ThepresenceofEPSwasevaluatedwithpreviouslydefinedstandardcriteria(ACCESS)andonlypatients withdefiniteandprobableinvolvementwereacceptedaspositive.SequenceSpecificOligonucletideProbesmethod was used for typing of HLA-DRB1 alleles from DNA samples in both groups. Results: The frequency of HLA DRB1*15 allele was more frequent in patients with sarcoidosis than controls (% 20.4 vs % 9.6)(pcorr=0.017). Ac- cordingtomultivariateanalysis(MVA),thepresenceofHLADRB1*15wasindicatedasanindependentriskfactor for sarcoidosis (OR:2.37; 95% CI: 1.31-4.30, p=0.004). Extra-pulmonary involvement was present in 39 patients (42.9%).Whenthepatientswithandwithoutextra-pulmonaryinvolvementcompared,HLADRB1*11allelewas significantlyhigherinpatientswithoutextra-pulmonarysarcoidosiswhichmaybeconcludedasaprotectiveallelefor systemic involvement (%30.8 vs. %15.4)(p<0.05).This result was also confirmed with the MVA (OR:0.35, %95 CI:0.15-0.84,p=0.018). Conclusions: WedemonstratedastrongpositivelinkbetweenthehaplotypeHLADRB1*15 andsarcoidosisinaTurkishCaucasianpopulationandapotentialprotectiveeffectofHLADRB1*11fromextra- pulmonaryinvolvementofdisease. (Sarcoidosis Vasc Diffuse Lung Dis 2014; 31: 154-162) Key words: Sarcoidosis,HLA-DRalleles,extra-pulmonaryinvolvement Received:18October2013 Correspondence:Dr.EzgiOzyilmaz CukurovaUniversityFacultyofMedicine DepartmentofPulmonaryDisease,Balcali,Adana,Turkey Phone:00905053841435 E-mail:ezgiozyilmaz@hotmail.com Original article: Clinical Research SARCOIDOSISVASCULITISANDDIFFUSELUNGDISEASES2014;31;154-162 ©Mattioli1885