The Role of Macrophages in Connective Tissue Disease-Associated Interstitial Lung Disease: Focusing on Molecular Mechanisms and Potential Treatment Strategies.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a severe manifestation of CTD that leads to significant morbidity and mortality. Clinically, ILD can occur in diverse CTDs. Pathologically, CTD-ILD is characterized by various histologic patterns, such as nonspecific interstitial pneumonia, organizing pneumonia, and usual interstitial pneumonia. Abnormal immune system responses have traditionally been instrumental in its pathophysiology, and various changes in immune cells have been described, especially in macrophages. This article first briefly overviews the epidemiology, clinical characteristics, impacts, and histopathologic changes associated with CTD-ILD. Next, it summarizes the roles of various signaling pathways in macrophages or products of macrophages in ILD, helped by insights gained from animal models. In the following sections, this review returns to studies of macrophages in CTD-ILD in humans for an overall picture of the current understanding. Finally, we direct attention to potential therapies targeting macrophages in CTD-ILD in investigation or in clinical trials, as well as the future directions regarding macrophages in the context of CTD-ILD. Although the field of macrophages in CTD-ILD is still in its infancy, several lines of evidence suggest the potential of this area.

HLA-DR genotypes in patients with systemic lupus erythematosus in Taiwan.

BACKGROUND: Different human leukocyte antigen (HLA)-DR genotypes have been known to be associated with the risk of development of systemic lupus erythematosus (SLE) in different populations, although Lu et al. have reported previously that no correlation exists between the HLA-DR genotype and disease manifestation in SLE patients in Taiwan. We investigated the effects different HLA-DR genotypes had on SLE incidence in Taiwanese patients as to whether risk alleles were associated with different clinical manifestations, and the effects risk alleles had on the age of disease onset. METHODS: Two hundred thirty-four SLE patients and 346 healthy controls were enrolled. HLA-DR genotyping was performed with the HLA FluoGene DRDQ kit for each subject. Chi-square tests and t tests were performed for statistical analysis. RESULTS: HLA-DR2 was significantly more frequently found in SLE patients than in controls (odds ratio [OR] = 2.05, 95% CI, 1.44-2.92, p < 0.001). Notably, HLA-DR6 appeared to trend toward negative correlation with SLE, whereas HLA-DR8 appeared to trend toward positive correlation. HLA-DR2 patients had an earlier onset of disease as well as a higher prevalence of oral ulcer, avascular necrosis of bone, and renal involvement (lupus nephritis). CONCLUSION: HLA-DR2 was associated with SLE susceptibility in this Taiwanese population as well as lower age of disease onset and more severe clinical manifestations.

Next-Generation Sequencing Profiles of the Methylome and Transcriptome in Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis.

Using next-generation sequencing to decipher methylome and transcriptome and underlying molecular mechanisms contributing to rheumatoid arthritis (RA) for improving future therapies, we performed methyl-seq and RNA-seq on peripheral blood mononuclear cells (PBMCs) from RA subjects and normal donors. Principal component analysis and hierarchical clustering revealed distinct methylation signatures in RA with methylation aberrations noted across chromosomes. Methylation alterations varied with CpG features and genic characteristics. Typically, CpG islands and CpG shores were hypermethylated and displayed the greatest methylation variance. Promoters were hypermethylated and enhancers/gene bodies were hypomethylated, with methylation variance associated with expression variance. RA genetically associated genes preferentially displayed differential methylation and differential expression or interacted with differentially methylated and differentially expressed genes. These differentially methylated and differentially expressed genes were enriched with several signaling pathways and disease categories. 10 genes (CD86, RAB20, XAF1, FOLR3, LTBR, KCNH8, DOK7, PDGFA, PITPNM2, CELSR1) with concomitantly differential methylation in enhancers/promoters/gene bodies and differential expression in B cells were validated. This integrated analysis of methylome and transcriptome identified novel epigenetic signatures associated with RA and highlighted the interaction between genetics and epigenetics in RA. These findings help our understanding of the pathogenesis of RA and advance epigenetic studies in regards to the disease.

Effects of virtual reality-augmented balance training on sensory organization and attentional demand for postural control in people with Parkinson disease: a randomized controlled trial.

BACKGROUND: There is a lack of studies related to virtual reality (VR)-augmented balance training on postural control in people with Parkinson disease (PD). OBJECTIVE: The purposes of this study were: (1) to examine the effects of VR-augmented balance training on the sensory integration of postural control under varying attentional demands and (2) to compare the results with those of a conventional balance training (CB) group and an untrained control group. DESIGN: A longitudinal, randomized controlled trial was used. SETTING: The intervention was conducted in the clinic, and the assessment was performed in a research laboratory. PATIENTS: Forty-two people with PD (Hoehn and Yahr stages II-III) were recruited. INTERVENTION: The VR and CB groups received a 6-week balance training program. MEASUREMENTS: The sensory organization tests (SOTs) of computerized posturography with single- and dual-task conditions were conducted prior to training, after training, and at follow-up. Equilibrium scores, sensory ratios, and verbal reaction times (VRTs) were recorded. RESULTS: There were no significant differences in equilibrium scores or VRTs between the VR and CB groups. However, the equilibrium scores in SOT-6 (ie, unreliable vision and somatosensation) of the VR group increased significantly more than that of the control group after training. The equilibrium scores in SOT-5 (ie, unreliable somatosensation with eyes closed) of the CB group also increased significantly more than that of the control group after training. LIMITATIONS: The functional significance of the improvements in equilibrium scores in the SOTs was not known, and the sample size was small. CONCLUSIONS: Both VR and CB training improved sensory integration for postural control in people with PD, especially when they were deprived of sensory redundancy. However, the attentional demand for postural control was not changed after either VR or CB training.