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This study aims to investigate genetic susceptibility to early-onset and late-onset anti-acetylcholine receptor antibody positive myasthenia gravis (EOMG and LOMG) and anti-muscle specific kinase antibody positive MG (MuSK-MG) at genome-wide level in a single population. Using a custom-designed array and imputing additional variants and the classical HLA alleles in 398 patients, we detected distinct associations. In EOMG, rs113519545 in the HLA class I region (OR = 5.71 [3.77-8.66], P = 2.24 x 10(-16)), HLA-B*08:01 (OR = 7.04 [3.95-12.52], P = 3.34 x 10(-11)) and HLA-C*07:01 (OR = 2.74 [1.97-3.81], P = 2.07(-9)), in LOMG, rs111256513 in the HLA class II region (OR = 2.22 [1.59-3.09], P = 2.48 x 10(-6)) and in MuSK-MG, an intronic variant within HLA-DQB1 (rs68081734, OR = 5.86, P = 2.25 x 10(-14)) and HIA-DQB1*05:02 (OR = 8.56, P = 6.88 x 10(-13)) revealed the most significant associations for genome-wide significance. Differential genetic susceptibility within the HLA to EOMG, LOMG and MuSK-MG has been established in a population from Turkey. (C) 2016 Elsevier Inc. All rights reserved.

Regulatory T cells were investigated in early-onset (EO) and late-onset (LO) myasthenia gravis patients with anti-acetylcholine receptor antibody (AChR-MG). Alterations in PD-1 and PD-L1 on CD4(+)CD25(++) (Treg) and responder T cells (Tresp, CD4(+)CD25(-)) were observed in LOMG patients. GITR was decreased on CD4(+)CD25(++) of all patients. Decrease of FOXP3 was associated with lower phosphorylation of STAT5.1,25-dihydroxyvitamin D3 (VitD3) increased suppression in co-culture with a stronger effect in patients by acting possibly both on cell groups. Changes in surface molecules and intracellular pathways contribute to the defects of Treg in non-thymomatous AChR-MG and VitD3 can have modulatory effects. (C) 2015 Elsevier B.V. All rights reserved.