The investigation of killer-cell immunoglobulin-like receptors (KIRs) and their HLA ligands in Iranian patients with myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a disabling disease with the underlying pathophysiology of auto-antibodies attacking the postsynaptic acetylcholine receptors of neuromuscular junctions causing muscle weakness. Natural killer (NK) cells are innate immune cells that play an important regulative role in immune responses. The human killer-cell immunoglobulin-like receptors (KIRs) family is one of the receptors on NK cells that can either activate or inhibit NK cells. This study aimed to assess the possible role of KIR and their human leukocyte antigen (HLA) ligand genes susceptibility to MG in Iranian patients. METHOD: One hundred and sixty-three patients with MG diagnosis based on the presence of clinical symptoms and laboratory tests and 400 healthy volunteers were studied. We used the polymerase chain reaction (PCR) technique for genotyping 15 KIRs and 5 HLA genes. RESULTS: The results demonstrated that there was no significant difference in the frequency of KIR genes and inhibitory KIR genotypes between controls and patients. In MG patients, HLA-C1Asn80 was significantly less frequent than in matched controls. The frequency of HLA genotype number 7 was significantly lower in MG cases, compared to the controls. Analysis of activating KIR genotypes showed that genotype number 10 was significantly less frequent in MG cases than in matched controls. CONCLUSION: Our results suggest that the presence HLA-C1Asn80 might play a protective role against the pathogenesis of MG. The significantly decreased prevalence of one activating KIR genotype and one of the HLA genotypes in MG cases suggest that these genotypes can reduce the risk of MG development. To specifically reveal the impact of KIR and HLA in MG, more studies are required.

Disease severity and response to treatment in Iranian patients with myasthenia gravis.

PURPOSE: Myasthenia gravis (MG) is a potentially fatal neuromuscular disorder if left untreated. In this study, we tried to address the possible demographic, clinical, and laboratory determinants of severity and outcome in Iranian MG patients over a follow-up period of more than 5 years. METHODS: Demographic and diagnostic data (age, age of onset, antibody status, thymus pathology, and duration of the disease) of the patients with MG were extracted. Maximal disease severity and post-intervention status were assessed according to the recommendations of the task force of the Myasthenia Gravis Foundation of America. RESULTS: In our series of 146 patients, MG was more severe in older, anti-muscle specific tyrosine kinase (MuSK) positive, and thymomatous patients. Seropositivity to the MuSK antibody and the presence of thymoma determined the need for immunosuppressive drugs. However, the number of patients requiring more than one immunosuppressive was not significantly different among various subtypes. CONCLUSIONS: The overall outcome was favorable in the majority of patients, despite differences in the disease course and severity. In contrary to the previous reports, anti-MuSK positive patients in our series did not need a more vigorous treatment regimen comparing other serologic subtypes of MG.

Association of HLA Class II Alleles with Disease Severity and Treatment Response in Iranian Patients with Myasthenia Gravis.

Myasthenia gravis is an autoimmune neuromuscular disease with a multifactorial etiology. A major part of the genetic susceptibility belongs to the HLA encoding genes. In this study, we investigated the role of HLA class II polymorphism in disease severity, and treatment response. In our 146 patients, 15 DRB1, 7 DQA1, and 9 DQB1 alleles, and 19 haplotypes were found. Adjusted p-values did not show any significant associations between these loci, disease severity and treatment outcome. Further studies in different populations with a larger number of patients are needed to determine the exact contribution of HLA class II alleles to MG prognosis.

Association of HLA class II (DRB1, DQA1, DQB1) alleles and haplotypes with myasthenia gravis and its subgroups in the Iranian population.

Heterogenic pattern of HLA associations with myasthenia gravis (MG) among different ethnicities and also among different MG subgroups has been the subject of debate in large series of many studies. One hundred and sixty Iranian MG patients were investigated for HLA class II (DRB1, DQA1, DQB1) associations compared to two hundred healthy controls from the same ethnic population. DRB1*11 DQA1*0501 DQB1*0301 haplotype was found to be protective for total (ocular plus generalized) MG (Pc=0.005, OR=0.49) and generalized MG (Pc=0.008, OR=0.49). DRB1*04 DQA1*0301 DQB1*0302 haplotype (Pc=0.03, OR=2.25) was predisposing for anti-acetylcholine receptor (AChR) antibody-positive MG, while DRB1*16 DQA1*0102 DQB1*05 (Pc=0.013, OR=4.28) was predisposing for anti-muscle specific tyrosine kinase (MuSK) antibody-positive MG. There was also a trend of positive association for DRB1*14 DQA1*0104 DQB1*05 haplotype with MuSK-positive MG (Pc=0.054, OR=3.97). Among other MG subgroups and with less significance, DRB1*0101 DQA1*0101 DQB1*05 haplotype (P=0.016, OR=3.68) had positive association with pure ocular MG, and DRB1*03 DQA1*0501 DQB1*0201 haplotype (P=0.024) had negative association with thymomatous MG. This study highlights the importance of appropriate MG subgrouping according to clinical and paraclinical characteristics in HLA studies among MG patients.