Systemic lupus erythematosus (SLE) is caused by a combination of genetic and environmental factors. Recently, analysis of a functional genome database of genetic polymorphisms and transcriptomic data ...from various immune cell subsets revealed the importance of the oxidative phosphorylation (OXPHOS) pathway in the pathogenesis of SLE. In particular, activation of the OXPHOS pathway is persistent in inactive SLE, and this activation is associated with organ damage. The finding that hydroxychloroquine (HCQ), which improves the prognosis of SLE, targets toll-like receptor (TLR) signaling upstream of OXPHOS suggests the clinical importance of this pathway. IRF5 and SLC15A4, which are regulated by polymorphisms associated with SLE susceptibility, are functionally associated with OXPHOS as well as blood interferon activity and metabolome. Future analyses of OXPHOS-associated disease-susceptibility polymorphisms, gene expression, and protein function may be useful for risk stratification of SLE.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Rheumatic diseases differ in severity and outcome across ethnic groups. Although genetic predisposition is an important factor influencing the development of rheumatic diseases, genomic data to date ...have been accumulated mainly in Europeans. However, East Asia has become an influential center for genetic studies worldwide, and there is also a growing need for a functional genome database for East Asians. Expression quantitative trait locus data for immune cell subsets can be extremely useful in interpreting the function of disease‐associated genetic polymorphisms. The development of a functional genome database for East Asians is expected to make a significant contribution to the understanding and stratification of the pathogenesis of rheumatic diseases in this population in the future.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Both genetic predisposition and environmental factors are involved in the development of rheumatoid arthritis（RA）. Based on epidemiological studies such as twin studies, the influence of genetic ...factors on the development of RA has been estimated to be about 50%. Among the genes associated with RA, the human leukocyte antigen（HLA）gene demonstrates the largest contribution. The HLA-DRB1 allele, which encodes an HLA-DR beta chain containing a five-amino acid sequence motif called a “shared epitope”（SE）, has traditionally been associated with RA. Recent genetic analysis has identified five amino acids in the HLA molecule that are particularly important in the association with RA, and the understanding of the association is steadily progressing. Interpreting the contribution of HLA is an important step in translating genomic information to clinical practice in RA. This review summarizes the relationship between HLA molecules and pathological or clinical parameters in RA.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive synovitis. It is significantly associated with disability, impaired quality of life, and premature mortality. Recently, ...the development of biological agents (including tumor necrosis factor-α and interleukin-6 receptor inhibitors) and Janus kinase inhibitors have advanced the treatment of RA; however, it is still difficult to predict which drug will be effective for each patient. To break away from the current therapeutic approaches that could be described as a “lottery,” there is an urgent need to establish biomarkers that stratify patients in terms of expected therapeutic responsiveness. This review deals with recent progress from multi-faceted analyses of the synovial tissue in RA, which is now bringing new insights into diverse features at both the cellular and molecular levels and their potential links with particular clinical phenotypes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Systemic lupus erythematosus (SLE) is characterized by immune system dysfunction and is clinically heterogeneous, exhibiting renal, dermatological, neuropsychiatric, and cardiovascular symptoms. ...Clinical and physiological assessment is usually inadequate for diagnosing and assessing pathophysiological processes in SLE. Clinical and immunological biomarkers could play a critical role in improving diagnosis, assessment, and ultimately, control of SLE. This article reviews clinical and immunological biomarkers that could diagnose and monitor disease activity in SLE, with and without organ-specific injury. In addition, novel SLE biomarkers that have been discovered through “omics” research are also reviewed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In the middle of the 20th century, biologists focused on investigating the mechanism of gene regulation and signal transduction in cells, which led to the concept that metabolites were products of ...gene expression and signal transduction pathways. In the 1920s, the importance of cellular metabolism was shown in the Warburg effect, in which cancer cells are characterized by a mitochondrial defect that shifts towards aerobic glycolysis. Recently, it is accepted that each organ and cell subset needs specific metabolic conditions and metabolic regulatory systems.
Immunometabolism is a relatively new field of metabolism studies. The immune system consists of various cell subsets that have unique requirements and functions. The metabolic reprogramming in each immune cell causes different effects on different cell subsets. For example, resting lymphocytes generate energy through oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO), whereas activated lymphocytes rapidly shift to the glycolytic pathway. A detailed understanding of metabolic regulation has progressed rapidly, especially in T cells during their differentiation from naïve to effector T cells.
Metabolism is now considered to play a key role in autoimmune diseases. Metabolic changes in autoimmune diseases might be due to inflammation as well as being involved in autoimmune pathogenesis. Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogenous clinical presentations whose precise pathophysiological mechanism is largely unknown. In this report, we review the altered metabolism in SLE and discuss the potential of metabolomics for accelerating the discovery of novel cellular autoimmune therapies and novel disease biomarkers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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