The macrophage immunometabolism regulator (MACIR) gene, also known as C5orf30, has emerged as a potential regulator of immune responses and inflammatory processes. Increasing evidence suggests that MACIR gene expression is associated with macrophage function, cellular metabolism, and inflammatory signalling, potentially contributing to the maintenance of immune homeostasis. Dysregulation of MACIR gene expression has been associated with pathological inflammatory responses and may play a role in the development and progression of autoimmune and chronic inflammatory diseases, particularly rheumatoid arthritis. However, the molecular mechanisms underlying the biological functions of MACIR remain incompletely understood. This review summarises current knowledge regarding the structure, expression, and regulation of the MACIR gene, with particular emphasis on its potential role in immune cell function and inflammatory signalling. The involvement of MACIR in rheumatoid arthritis and other immune-mediated diseases is discussed, together with emerging evidence linking MACIR to immunometabolism and disease-associated cellular responses. Furthermore, the potential of MACIR as a biomarker and therapeutic target is considered. A better understanding of the mechanisms regulating MACIR gene expression may provide new insights into the pathogenesis of inflammatory and autoimmune diseases and contribute to the development of novel diagnostic and therapeutic strategies.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex, multifactorial aetiology, in which both environmental factors and genetic predisposition play a significant role. This narrative review summarises the genetic polymorphisms associated with RA that have been identified by genome-wide association studies (GWAS). Its aim is to synthesise the loci and single-nucleotide polymorphisms (SNPs) reported to date, to relate them to the immunological mechanisms through which they are thought to act, and to assess their emerging diagnostic, prognostic, and pharmacogenomic applications. Its scope covers large-scale GWAS and multi-ancestry meta-analyses together with the candidate-gene, functional, and pharmacogenomic studies required for their interpretation. Three principal conclusions emerge from the literature reviewed. First, the genetic architecture of RA remains dominated by the HLA-DRB1 shared epitope, which is associated primarily with seropositive, anti-citrullinated protein antibody-positive disease, whereas the numerous non-HLA loci identified to date each confer only a modest individual effect. Second, these non-HLA variants converge on a limited number of biological processes—the activation thresholds of T and B lymphocytes, NF-κB and JAK–STAT cytokine signalling, and the invasive behaviour of fibroblast-like synoviocytes—so that their value lies less in the prediction of risk by individual variants than in identifying pathways amenable to therapeutic targeting. Third, the most readily translatable findings are pharmacogenomic. Variants affecting adenosine signalling and nucleotide metabolism modulate the response to methotrexate. Several polymorphisms predict the response to TNFα inhibitors. Polygenic risk scores are beginning to support the differential diagnosis of early inflammatory arthritis. Progress remains constrained by the over-representation of European-ancestry cohorts, by the difficulty of moving from an associated locus to a causal variant and its target gene, and by the limited replication of pharmacogenomic associations. Integration of genomic with transcriptomic, epigenomic, proteomic, and metabolomic data, supported by machine learning approaches, is therefore required before genotype-guided management of RA can enter routine clinical practice.

Diabetes mellitus is a chronic and progressive metabolic disorder associated with abnormal blood glucose levels. The term involves several diseases with different pathophysiology mechanisms and treatment strategies. Stem cell-based treatments represent an emerging strategy for patients with diabetes mellitus with severe pancreatic insufficiency and poor glycemic control. Over the last 20 years, researchers have investigated mesenchymal stem cell infusion and the transplantation of stem cell-derived β cells and islet tissues. This review aims to comprehensively discuss the latest advances in the field of stem cell use in diabetes, including clinical studies and preclinical experiments aiming at improving the efficacy and safety of stem cell use.