Study On The Association Between HLA-B51 And Behcet's Disease, As Well As The Effect Of Th1,Th2 Cytokines And IL-17 In The Pathogenesis Of Behcet's Disease

Part One Clinical analysis of 128 cases with Behcet's diseaseObjective:To determine the clinical patterns of patients with Behcet's disease(BD).Methods:Clinical data of 128 cases with Behcet's disease admitted toDermatology Department of Huashan Hospital,Fudan University from January 1996to January 2008 were collected.The clinical manifestations were analyzedretrospectively,including its prevalence by gender and age,various organ and systeminvolvement,and the differences between male and female patients.Results:Meanage at onset of these 128 patients was (32.0±12.1) years,with an average length ofclinical course of 5 (1～10) years.Oral aphtha ulcer was found in all of these 128(100%) patients,and then followed by skin lesions in 115 cases (89.8%),genitalulcer in 92 cases(71.9%),positive for the pathergy test in 70 cases(54.7%),and eyesinvolvement in 38 cases (29.7%).18 of 61 cases (29.5%) were positive in HLA-B51gene test.Oral aphtha ulcer was the initial sign for 91 cases out of 128 cases,thenfollowed by skin lesions in 69 cases,genital ulcer in 61 cases,and eyes involvementin 15 cases.Significant difference between male and female patients could be seen intheir clinical manifestations,such as the incidence of BD,various types of skin lesions,eyes or nerves involvement and related lab findings.Conclusions:Multiple organsand systems could be involved in Behcet's disease with a significant difference ofclinical manifestations between male and female patients.A good knowledy about theclinical patterns of Behcet's disease should be dissemiated among clinicaldermatologists so as to decrease the rate of misdiagnosis.Part Two Study on the association between HLA-B51 and Chinesepatients of Han nationality with Behcet's diseaseObjective:To investigate the association between HLA-B51 allele and Behcet's disease (BD).Methods:61 Chinese patients of Han nationality with BD diagnosedaccording to the International Study Group (ISG) criteria were included.The controlgroup consisted of 100 healthy individuals.HLA-A and HLA-B genes wereundertaken by means of reverse PCR-sequence specific oligonucleotide (SSO)method.HLA-B51 allele (HLA-B5101～HLA-B5109) genotyping was performedwith the PCR-sequence specific primer (SSP) method.Results:Compared with thecontrol group(11 positive,11%),a significant HLA-B51 association with BD patients(18 positive,29.5%) was determined (P_c〈0.05,RR=3.39).The frequency of theHLA-B46 gene in patients with BD was also higher than that of control group.(P_c〈0.05,RR=2.39). All HLA-B51 positive patients and controls carried onlyHLA-B5101 allele,and no other alleles were found.Great differences in clinicalmanifestations have been observed in HLA-B5101 positive and negative patients.Significant association of HLA-B5101 with gender and clinical type and age of onsetof BD have been found.Conclusions:This study supports HLA-B51 is one of thesusceptible genes of BD in Chinese Han nationality and reveals strong associationbetween HLA-B5101 and Chinese male BD patients of Han nationality,clinical typeof BD,as well as the age of the onset of BD.The increased frequency of HLA-B46gene in BD patients may be due to the linkage disequilibrium of some of the HLAhaplotype combined in BD patients.Part three Study on the effect of Th1,Th2 cytokines and IL-17 inthe pathogenesis of Behcet's diseaseObjective:To analyse the expression of Th1,Th2 cytokines and IL-17 in patientswith Behcet's disease (BD) in relation to their disease activity.Methods:45 BDpatients (25 in active stage) were investigated with ELISA to determine theircytokines levels,including IL-12,IL-10,IFN-γand IL-17.Results:Active and inremission BD patients showed significant increase in their serum levels of Th1 (IFN-γ,IL-12) and Th2 (IL-10) cytokines,as well as IL-17.Active BD was characterized by a higher increase of IL- 17 (43.3±11.9pg/ml :21.2±7.5pg/ml,P〈0.05) and IFN-γ(32.1±3.7pg/ml :18.1±3.1pg/ml,P〈0.05),compared to BD patients inremission stage.There was no significant differerce between two clinical patterns ofBD in serum levels of Th1 and Th2 cytokines and IL-17.Conclusions:Our resultssuggest that both Th1 and Th2 cytokines paly a role in the pathogenesis of BD.themicroenvironment of CD4+ T cells in active BD patients may induce the productionof more cells committed to Th1 than those of BD patients in remission and healthycontrols.IL-17 could be a good indicator of disease activity and also paly a role in thepathogenesis of BD.