Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2016
Human Leucocyte Antigen B50 Is Associated with Conversion to Generalized Myasthenia Gravis in Patients with Pure Ocular Onset.
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Tiftikcioglu Bedile Irem, Uludag Irem Fatma, Zorlu Yasar, Pirim İbrahim, Sener Ufuk, Tokucoglu Figen, Korucuk Meltem
Аннотация
OBJECTIVES: The aim of this study was to investigate the associations between major histocompatibility complex (MHC) class I and II alleles and disease characteristics in Turkish patients with myasthenia gravis (MG).
SUBJECTS AND METHODS: The MHC class I and II alleles of 108 unrelated MG patients were genotyped. The human leucocyte antigen (HLA) distribution of all MG patients and subgroups of MG patients (grouped according to disease characteristics) was compared to that of 250 healthy controls.
RESULTS: Overall distributions of HLA-B*61 and C*05 were more frequent in MG patients (7.4 vs. 2.0% and 14.8 vs. 6.8%, respectively) than in non-MG patients. Subgroup analyses revealed that HLA-DRB1*14 and DQB1*02 alleles were more frequent in early-onset MG [n = 10 (20.8%) vs. n = 25 (10.0%) and n = 21 (43.8%) vs. n = 59 (23.6%)]. In patients seropositive for anti-AchR antibodies, the frequencies of HLA-B*50 and C*05 were higher. HLA-C*05, DRB1*01, and DRB1*11 were higher in patients with ocular MG. In addition, HLA-A*01, A*31, B*08, and DRB1*14 were higher among patients with thymic hyperplasia, whereas DQB1*03 was lower. However, all of these differences lost significance after correction of the p value for multiple comparisons. No allele association was found among patients with thymoma. Strikingly, patients with generalized MG who had pure ocular symptoms at disease onset had significantly increased HLA-B*50 compared to the controls (corrected p < 0.001, OR = 9.92; 95% CI 3.05-32.22).
CONCLUSION: The HLA-B*50 allele was associated with conversion to generalized disease in patients with pure ocular symptoms at disease onset. This finding could extend our understanding of the complex interactions between the pathogenesis of MG and genetic heritage.
SUBJECTS AND METHODS: The MHC class I and II alleles of 108 unrelated MG patients were genotyped. The human leucocyte antigen (HLA) distribution of all MG patients and subgroups of MG patients (grouped according to disease characteristics) was compared to that of 250 healthy controls.
RESULTS: Overall distributions of HLA-B*61 and C*05 were more frequent in MG patients (7.4 vs. 2.0% and 14.8 vs. 6.8%, respectively) than in non-MG patients. Subgroup analyses revealed that HLA-DRB1*14 and DQB1*02 alleles were more frequent in early-onset MG [n = 10 (20.8%) vs. n = 25 (10.0%) and n = 21 (43.8%) vs. n = 59 (23.6%)]. In patients seropositive for anti-AchR antibodies, the frequencies of HLA-B*50 and C*05 were higher. HLA-C*05, DRB1*01, and DRB1*11 were higher in patients with ocular MG. In addition, HLA-A*01, A*31, B*08, and DRB1*14 were higher among patients with thymic hyperplasia, whereas DQB1*03 was lower. However, all of these differences lost significance after correction of the p value for multiple comparisons. No allele association was found among patients with thymoma. Strikingly, patients with generalized MG who had pure ocular symptoms at disease onset had significantly increased HLA-B*50 compared to the controls (corrected p < 0.001, OR = 9.92; 95% CI 3.05-32.22).
CONCLUSION: The HLA-B*50 allele was associated with conversion to generalized disease in patients with pure ocular symptoms at disease onset. This finding could extend our understanding of the complex interactions between the pathogenesis of MG and genetic heritage.