Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10(-9); and rs189754752, OR = 2.47, p = 4.22 × 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10(-8)).

Objective Takayasu’s arteritis is a rare large vessel vasculitis with incompletely understood etiology. We performed the first unbiased genome-wide association study (GWAS) in Takayasu’s arteritis. Methods Two independent Takayasu’s arteritis cohorts from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 European-derived patients and 1,047 controls. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu’s arteritis. Results We identified genetic susceptibility loci for Takayasu’s arteritis with a genome-wide level of significance in IL6 (rs2069837, OR= 2.07, P= 6.70×10−9), RPS9/LILRB3 (rs11666543, OR= 1.65, P= 2.34×10−8), and an intergenic locus on chromosome 21q22 (rs2836878, OR= 1.79, P= 3.62×10−10). The genetic susceptibility locus in RPS9/LILRB3 is located within the leukocyte receptor complex (LRC) gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P= 2.29×10−8). In addition, we identified candidate susceptibility genes with suggestive levels of association (P <1×10−5) including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B in Takayasu’s arteritis. Conclusion This study identified novel genetic susceptibility loci for Takayasu’s arteritis and uncovered potentially important aspects in the pathophysiology of this form of vasculitis.

The objective was to investigate the predictive factors for avascular necrosis (AVN) of bone in patients with systemic lupus erythematosus (SLE). The records of 868 patients with SLE from four centers were reviewed retrospectively. Forty-nine patients with AVN were identified. A total of 154 patients with SLE who did not have clinically apparent AVN during the follow-up were evaluated as a control group. The demographic, clinical, laboratory and management characteristics of these two groups of patients were recorded according to predefined protocol and compared. The prevalence of AVN was detected 6% in our SLE population. The highest dose corticosteroid administered within 4 months and total cumulative prednisolone dose were significantly higher in the SLE patients with AVN. The use of cytotoxic agent significantly higher proportion of patients with AVN. AVN tends to develop more frequently in male gender and younger patients. Oral ulcer, pleuritis, Raynaud's phenomenon, cutaneous vasculitis, lymphadenopathy, autoimmune thyroiditis, peripheral neuropathy and Sjögren's syndrome were higher incidence in SLE patients with AVN. The bilateral femoral heads were the commonest site of involvement of AVN in our patients with SLE.

The authors have proposed a control system of a quadruped locomotion robot by using nonlinear oscillators. It is composed of a leg motion controller and a gait pattern controller. The leg motion controller drives the actuators of the legs by using local feedback control. The gait pattern controller involves nonlinear oscillators with mutual interactions. In this paper, capability of adaptation of the proposed control system against variance of the environment is verified through numerical simulations and hardware experiments: With the input signals from the touch sensors at the tips of the legs, the nonlinear oscillators tune the phase differences among them through mutual entrainments. As a result, a gait pattern corresponding to the states of the system or to the properties of the environment emerges. And the robot changes its gait pattern adaptively to variance of the environment and establishes a stable locomotion while suppressing the energy consumption.