Introduction: Ankylosing spondylitis (AS) is a familial, heritable disease specified by syndesmophyte formation leading to an ankylosed spine. Endoplasmic reticulum aminopeptidase 1 (ERAP1) genetic variations have been widely proved to be associated with AS in several ethnic populations. The aim of this study was to investigate whether ERAP1 single nucleotide polymorphisms (SNPs) are associated with AS susceptibility and disease severity in Taiwanese.Methods: Four ERAP1 SNPs (rs27037, rs27980, rs27044 and rs30187) were genotyped in 797 Taiwanese AS patients and 1,150 healthy controls. Distributions of genotype and alleles were compared between AS patients and healthy controls, and among AS patients stratified by clinical parameters.Results: The SNP rs27037T allele appeared to be a risk factor for AS susceptibility (P= 5.5 × 10^-5, OR 1.30, 95% CI: 1.15 to 1.48; GT+TT vs. GGP= 9.3 × 10^-5, OR 1.49, 95% CI: 1.22 to 1.82). In addition, the coding SNP (cSNP) rs27044G allele (P= 1.5 × 10^-4, OR 1.28, 95% CI: 1.13 to 1.46; CG+GG vs. CC,P= 1.7 × 10^-3, OR 1.44, 95% CI: 1.15 to 1.81) and the cSNP rs30187T allele (P= 1.7 × 10^-3, OR 1.23, 95% CI: 1.08 to 1.40; CT+TT vs. CCP= 6.1 × 10^-3, OR 1.38, 95% CI: 1.10 to 1.74) were predisposing factors for AS. Notably, the rs27044G allele carriers (CG+GG vs. CC,P= 0.015, OR 1.59, 95% CI: 1.33 to 2.30) and rs30187T allele carriers (CT+TT vs. CC,P= 0.011, OR 1.63, 95% CI: 1.12 to 2.38) were susceptible to syndesmophyte formation in AS patients. Furthermore, two cSNPs (rs27044 and rs30187) strongly associated with HLA-B27 positivity in AS patients. Finally, the ERAP1 SNP haplotype TCG (rs27037T/rs27980C/rs27044G) is a major risk factor for AS (adjustedP<0.00001, OR 1.38, 95% CI: 1.12 to 1.58) in Taiwanese.Conclusions: This study provides the first evidence of ERAP1 SNPs involving syndesmophyte formation. The interactions between ERAP1 SNPs and HLA-B27 play critical roles in pMHC I pathway processing contributing to the pathogenesis of AS in multiple populations.

Background: Oropharyngeal dysphagia is common after a stroke. Understanding the physiology of swallowing and its coordination with respiration in stroke recovery is crucially important.Methods: A non‐invasive swallowing assessment method was used to detect oropharyngeal swallowing and respiration coordination simultaneously during the swallowing process. This system detected movement of the larynx, submental muscle activity, and nasal airflow. Six different sizes of water boluses (maximum of 20 mL) were swallowed and assessed for each subject.Key Results: We recruited 59 healthy participants and 38 first ever unilateral stroke patients completed baseline and follow‐up assessments at 3, 6, and 9 months poststroke. The results showed that oropharyngeal swallowing parameters in unilateral stroke deviate from normal patterns. For respiration coordination, the unilateral stroke group had longer swallowing apnea duration but similar frequencies of pre‐ and postswallowing respiratory phase patterns compared with the healthy controls. The probability of piece‐meal deglutition was higher in the stroke group than in the control group. Additionally, there were gradually decreasing piece‐meal deglutition probabilities among the stroke patients at follow‐up, and none differed statistically from those of the controls at 6 months poststroke.Conclusions & Inferences: The non‐invasive swallowing and respiration assessment method applied in this study detected the changes manifested in swallowing and respiration during the subacute phase of recovery in 6 months after a unilateral stroke. The study results serve as a baseline for further research and help advance dysphagia research methodologies. These assessments may be combined with bedside evaluations for clinical application.

HCMV phosphoprotein 65 (HCMVpp65) is a putative immunogen that acts as an accelerator, inducing autoantibody and exacerbating autoimmune response in susceptible animals. The immunity to pp65336-439 instigates autoimmunity, suggesting that pp65336-439 contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65422-439 for immunization of BALB/c mice and mapping of B cell epitope. The target epitope pp65422-439 reactivity and B cell epitope mapping was examined in serum from pp65422-439-immunized mice and patients with systemic lupus erythematosus (SLE). Kidney tissue from immunized mice was examined for signs of immune complex nephritis. Anti-pp65422-439 antibody in serum either from patients with SLE or from pp65422-439-immunized mice exhibited cross-reactivity to several nuclear components such as double-stranded DNA (dsDNA). Moreover, the pp65422-439-immunized mice developed initial signs of glomerulonephritis such as deposition of immunoglobulin G/M (IgG/IgM) and third complement component (C3). With B cell epitope mapping by pp65422-439-derived decapeptides, one dominant epitope, pp65428-437, was identified in serum from pp65422-439-immunized mice and patients with SLE with anti-pp65422-439 antibody. Epitope spreading from pp65428-437 to pp65430-439 was found in pp65422-439-immunized mice in which we generated monoclonal antibodies to pp65425-434 and pp65430-439. However, dsDNA positive reactivity was exclusively observed in Crithidia luciliae stains with pp65430-439-reactive monoclonal antibody. Additionally, we observed the amelioration of autoimmunity following the elevation of IgM targeting pp65428-437. Our data suggest that pp65428-437 may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that leads to spinal ankylosis. The receptor activator of the nuclear factor-kappa (RANK), RANK ligand, and osteoprotegerin (OPG) (RANK/RANKL/OPG) pathway plays critical roles in bone metabolism and the immune system. The current study was aimed at investigating whether six single-nucleotide polymorphisms (SNPs) within the RANK, RANKL, and OPG genes essential for bone homeostasis are associated with AS. Genotype distributions, allele and haplotype frequencies, were compared between 1120 AS patients and 1435 healthy controls and among AS patients with stratification by syndesmophyte formation, onset age, and HLA-B27 positivity. We found that RANKL SNPs were associated with AS syndesmophyte formation. Notably, the RANKL SNP haplotype rs7984870C/rs9533155G/rs9525641C was negatively associated with AS susceptibility and appeared to protect against syndesmophyte formation in AS. Functionally, RANKL promoter SNPs (rs9525641 C/T and rs9533155 G/C) affected DNA-protein complex formation and promoter activity in promoter reporter analyses. The OPG SNP haplotype rs2073618G/rs3102735T was significantly associated with HLA-B27 negativity in AS patients. Furthermore, AS patients with syndesmophyte formation had significantly lower levels of soluble RANKL levels than those without syndesmophyte formation. Our data suggested a role for RANKL in AS susceptibility and severity.

To illustrate the clinical presentation, diagnosis, management, and outcome of unilateral right occipital condyle to C2 level spinal cord infarction. A teaching hospital in Taiwan. A 37-year-old man presented with acute-onset severe right neck pain before weakness developed in both right limbs. Early diagnosis was delayed due to mild intervertebral herniation of the C4-C5 disk. Magnetic resonance imaging revealed unilateral right occipital condyle to C2 level infarction. Angiography showed stenosis of the right vertebral artery (foraminal and intradural segments), and dissection of the left vertebral artery at the C1-C2 level. At discharge, he walked with assistance; 2 weeks later, he walked independently. An early diagnosis is difficult but important, as it facilitates appropriate treatment for better functional and survival outcomes. Accurate early diagnosis can be made with adequate knowledge of spinal cord infarction and high index of suspicion for this condition.

MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (P_FDR = 2.25 × 10⁻¹¹⁵; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (P_FDR = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and HLA-B27 positivity (P_FDR = 1.45 × 10⁻³³; OR, 28.79; 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.