The Association Between HLA-DRB1 Alleles Polymorphism, ANCA And Susceptibility To Antithyroid Drug Induced Leucocytopenia In Patients With Graves Disease

Objective To investigate the relationship between HLA-DRB1 alleles polymorphism, antineutropil cytoplasmic antibody (ANCA) and susceptibility to Antithyroid drug-ind- uced leucocytopenia in patients with Graves disease (GD) in Anhui Han Chinese.Methods①The HLA-DRB1*08032, DRB1*1501 and DRB1*0901 allele frequencies were determined by the polymerase chain reaction based sequence-specific primer (PC- R-SSP) method in 76 patients with Graves disease who had Antithyroid drug(ATD) induced leucocytopenia and 98 patients with Graves disease treated with ATD, who were free from leucocytopenia and 230 healthy Controls.②Indirect immu- nofluorescence assay (IIF) was used to detect ANCA;Positive, then further EUROA- SSAY were used to detect anti-Myeloperoxidase(MPO) antibody and anti-Proteinase- 3(PR3) antibody in sera from 76 patients with Graves disease who had Antithyroid drug(ATD) -induced leucocytopenia and 98 patients with Graves disease treated with ATD, who were free from leucocytopenia.Result①compared with controls,The allele frequencies of DRB1*08032 and DRB1*1501 were obviously increased(p=0.00,OR=3.06;p=0.042,OR=1.77),while that of HLA-DRB1*0901 were significantly decreased (p=0.01,OR=0.33)in Antithyroid drug-induced leucocytopenia patients.②compared with GD patients without leucocynt- openia, The allele frequencies of DRB1*08032 and DRB1*1501 were obviously increased(p=0.001,OR=4.03;p=0.016,,OR=2.28),while that of HLA-DRB1 *0901 were significantly decreased (p=0.023,OR=0.43) in Antithyroid drug-induced leucocytopenia patients.③compared with controls,the allele frequencies of HLA-DRB1*0803- 2,DRB1*1501 and DRB1*0901 had no statistically significant diff- erence in GD patients without leucocytopenia (p>0.05).④compared with GD patients treated with MMI who were free from leucocytopenia, the ANCA frequencies were obviously increased in GD patients who had MMI-induced leucocytopenia (x~2=4.878,p=0.027) ; compared with GD patients treated with PTU who were free from leucocytopenia, the ANCA frequencies were increased in GD patients who had PTU-induced leucocytopenia,but the difference was not statistically significant (p=0.404); Whether in GD patients with leucocytopenia or in GD patients without leucocytopenia,compared with GD patients treated with MMI , the ANCA frequencies were increased in GD patients treated with PTU, but the difference was not statistically significant (x~2=0.287,p=0.592;x~2=0.141,p=0.707).⑤Whether in GD patients with leucocytopenia or in GD patients without leucocytopenia,compared with GD patients who is not carrying DRB1 *08032, DRB1*1501,DRB1*0901 allele, the ANCA frequencies were significantly increased in GD patients who is carrying it(p<0.05); compared with GD patients who is carrying DRB1 *0901allele, the ANCA frequencies were decreased in GD patients who is carrying it,but the difference was not statistically significant (p>0.05).⑥The difference in thyroxine between GD patients with leuc- ocytopenia and GD patients without leucocytopenia was not statistically significant (p>0.05); The difference in the thyroid-ralated antibodies between GD patients with leucocytopenia and GD patients without leucocytopenia was not statistically significant(p>0.05).Conclusion①The DRB1*08032,HLA-DRB1*1501 alleles may be susceptible genes to Antithyroid drug -induced leucocytopenia in Anhui; while HLA-DRB1*0901 alleles may be protective genes or resistant genes.②Immune response may be involved in its development.③ANCA may be associated with whether the patient carrys a certain allele.The occurrence of immune response is based on the genetic susceptibili- ty.④There may be no correlation between Antithyroid drug -induced leucocytopenia and the elevation in thyoxine and the positive thyroid-related antibodies in GD patients.