Immuno

Sjögren’s syndrome (SS) is a chronic autoimmune disease primarily affecting the lacrimal and salivary glands, characterized by ocular and oral dryness. Beyond exocrine dysfunction, SS may also involve multiple organs and systems, contributing to systemic complications that impair a patient’s quality of life. Among these, ocular inflammation represents a significant clinical challenge, manifesting as dry eye disease and other vision-affecting complexities. Despite advances in SS understanding, the inflammatory mechanisms driving ocular manifestations remain incompletely elucidated. This review aims to clarify the key inflammatory pathways underlying ocular complications in SS and the clinical implications. Additionally, it discusses both conventional and novel therapeutic strategies focusing on mitigating SS-associated ocular inflammation, including targeted immunomodulatory agents, regenerative medicine, and innovative drug delivery systems. By integrating current knowledge from recent studies, this review attempts to provide researchers and clinicians with a comprehensive resource for optimizing SS treatment approaches. The advancement of targeted therapies and emerging mitigation strategies holds promise for improving patient outcomes and enhancing SS management. Full article

Background: High-grade serous ovarian cancer (HGSOC) is a highly aggressive malignancy with poor prognosis due to late-stage diagnosis and limited treatments. Identifying differentially expressed genes (DEGs), and immune cell infiltration patterns may improve prognostic assessment and therapeutic strategies. Methods: We conducted a meta-analysis of gene expression data from the GEO (Gene Expression Omnibus, NCBI). DEGs were identified, functionally enriched, and analyzed for protein-protein interactions. Overlaps with oncogenes and tumor suppressor genes were examined. Cox survival analysis and a gene expression-based risk stratification model were developed. Immune infiltration differences were assessed using deconvolution methods. Results: A total of 11 studies (291 HGSOC, 96 controls) identified 892 DEGs, mainly involved in mitochondrial function, vesicle trafficking, and immune regulation. Key oncogenes (EZH2, PDK1, ERBB2) and tumor suppressor genes (BRCA1, DUSP22) were identified. Survival analysis associated the expression of SEC24B, TGOLN2, TRAK1, and CAST with poor prognosis. Low-risk patients had higher activated dendritic cells and CD4+ memory T cells while high-risk patients were enriched in common lymphoid progenitors and megakaryocyte-erythroid progenitors. Conclusions: This study identifies key DEGs in HGSOC progression and presents a risk stratification model predicting patient outcomes. Full article

The sympathetic nervous system (SNS) is crucial for stress response regulation and immune modulation. Prolonged SNS activation, often induced by stress exposure, disrupts immune homeostasis and intensifies inflammatory processes, contributing to periodontal disease progression. This study investigates the relationship between SNS activity and periodontitis severity, utilizing salivary biomarkers chromogranin A (CgA) and alpha-amylase (sAA) alongside pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6). Saliva samples from 67 patients, categorized by periodontitis severity (Stages I/II and III/IV), were analyzed using enzyme-linked immunosorbent assay (ELISA). The results revealed significantly higher median levels of CgA (9.45 vs. 3.93 pmol/mL) and IL-1β (257.81 vs. 220.11 pg/mL) in patients with Stage III/IV periodontitis compared with those with Stage I/II, indicating heightened SNS activity and inflammatory response. Correlations between these biomarkers and clinical periodontal parameters, such as probing depth and clinical attachment loss, further support these findings. Despite elevated sAA levels in severe cases, statistical significance was not achieved. IL-6 levels also showed no significant variation across disease stages, although trends aligned with increased severity. This study highlights the interplay between SNA activation and periodontal inflammation, as evidenced by elevated salivary levels of CgA and IL-1β in patients with advanced periodontitis. By integrating neuroendocrine and inflammatory biomarkers into the diagnostic process, clinicians may be able to better identify patients at increased risk for periodontal breakdown and to consider adjunctive interventions such as stress management, thereby supporting more personalized approaches to periodontitis treatment. Full article

Background: A novel and highly effective strategy for tumor immunotherapy involves enhancing host immune responses against tumors through the blockade of checkpoint molecules. The most common toxicities associated with checkpoint blockade therapies include autoimmune damage to various organs. Purpose: This study aims to investigate hematological markers derived from complete blood counts (CBCs)—including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (dNLR), white blood cell-to-hemoglobin ratio (WHR), neutrophils, lymphocytes, platelets, hemoglobin, red blood cell (RBC) count, neutrophil-to-RBC ratio (NRR), and neutrophil-to-hemoglobin ratio (NHR)—as potential prognostic biomarkers for the early identification of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 immune checkpoint inhibitors. Materials and Methods: A prospective observational study was conducted on 44 patients with stage III-IV solid tumors treated with immune checkpoint (PD-1 or PD-1/CTLA-4) inhibitors. Thyroid function tests and CBC-derived biomarkers were collected at baseline, before immunotherapy. In the immunotherapy cohort, 15 of the 44 patients developed immune-related hypothyroidism, defined as overt autoimmune thyroiditis (TSH > 4.0, FT4 < 12, and anti-TPO antibodies > 30 IU/mL and/or anti-TG antibodies > 95 IU/mL) (Group 1). In comparison, 29 patients maintained normal thyroid function (Group 2). The control group comprised 14 age- and sex-matched healthy volunteers (Group 3). Statistical analyses were performed using analysis of variance (ANOVA) to compare blood parameters among the three groups (Group 1, Group 2, and Group 3) before treatment, with statistical significance set at a p-value < 0.05. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic power of the potential prognostic biomarkers areas. The area under the curve (AUC), sensitivity, and specificity were calculated for the 44 immunotherapy patients. Results: The PLR was significantly higher (262.25 ± 162.95), while WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes were lower (2.07 ± 0.66, 0.54 ± 0.19, 0.96 ± 0.28, 0.36 ± 0.14, 6.36 ± 2.07, 4.29 ± 1.55, and 1.23 ± 0.41, respectively) at baseline in Group 1 in comparison to Group 2. ROC curve analysis revealed that the areas under the curve (AUC) for WBCs, neutrophils, lymphocytes, WBCs-neutrophils, the PLR, the WHR, the NRR, and the NHR were 0.9, 0.87, 0.83, 0.85, 0.84, 0.92, 0.89, and 0.87, respectively. These values exceeded the threshold, indicating the high prognostic potential of each marker. Conclusions: Lower baseline levels of WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes, along with a higher PLR, were associated with an increased risk of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 inhibitors. These CBC-derived biomarkers represent simple, accessible, and potentially useful tools for predicting hypothyroidism in cancer patients undergoing immunotherapy. Further studies in bigger cohorts are needed to validate our findings. Full article

Antibody-dependent enhancement (ADE) is a well-established mechanism of pathology in several viral diseases, but its relevance in COVID-19 is not yet recognized. Although several studies in humans have shown an association between antibody responses and disease severity, long term studies addressing the presence of antibodies before infection and their neutralization capacity are needed to establish ADE. Mechanistic studies have determined that the entry of SARS-CoV-2 into host cells can be mediated by immune complexes through Fcγ receptors or by favoring ACE2 conformation. However, the impact on viral replication is not clear. There is evidence for enhancing effects of immune complexes on Fcγ receptor-mediated effector mechanisms and cytokine secretion after modulation of cell signaling in immune cells, specially by antibodies with altered glycosylation, which points to ADE that can contribute to COVID-19 pathology. However, more studies are needed to determine the impact of antibodies both in naturally infected and vaccinated subjects, which can lead to their use as a prognostic marker and increase vaccine safety. Full article

Honey and other bee products, including propolis, royal jelly, and bee pollen, are widely recognized for their medicinal properties. Among their numerous biological activities, their anti-inflammatory and immunomodulatory effects have gained significant attention in recent years. Immune and inflammatory disorders contribute significantly to the development of chronic conditions, including cancer and diabetes. Bee-derived products, along with their bioactive compounds such as polyphenols, have shown promising therapeutic effects in modulating inflammatory mediators. Studies indicate that these products help regulate tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), and interleukin-7 (IL-7) levels while reducing reactive oxygen species (ROS) production. Additionally, both in vitro and in vivo research, along with clinical studies, highlight their role in enhancing immune responses by activating B and T lymphocytes. This review explores the molecular mechanisms underlying these properties, emphasizing the role of bioactive compounds such as flavonoids, phenolic acids, and proteins in modulating immune responses and reducing inflammation. Evidence from in vitro, in vivo, and clinical studies suggests that honey and bee products influence cytokine production, regulate immune cell activity, and mitigate oxidative stress, making them potential therapeutic agents for inflammatory and immune-related disorders. To gather relevant information, databases such as Google Scholar, PubMed, and ScienceDirect were searched using various keyword combinations, including immunomodulatory, anti-inflammatory, bee products, honey, propolis, royal jelly, bee venom, and bee pollen. Given their anti-inflammatory, immune-protective, antioxidant, anti-apoptotic, and antimicrobial properties, bee products remain a subject of interest for further clinical evaluation. Full article

This review aims to explore the role of immunotherapeutic strategies—primarily intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and selected immunomodulatory agents—in the treatment of neurological and psychiatric disorders with suspected or confirmed autoimmune mechanisms. A central focus is placed on understanding the immunopathology of these conditions through the identification and characterization of disease-associated autoantibodies. Disorders such as autoimmune encephalitis, myasthenia gravis, limbic epilepsy, neuropsychiatric systemic lupus erythematosus (NPSLE), and certain forms of schizophrenia have shown clinical responses to immunotherapy, suggesting an underlying autoimmune basis in a subset of patients. The review also highlights the diagnostic relevance of detecting autoantibodies targeting neuronal receptors, such as NMDA and AMPA receptors, or neuromuscular junction components, as biomarkers that guide therapeutic decisions. Furthermore, we synthesize findings from published randomized controlled trials (RCTs) that have validated the efficacy of IVIG and PLEX in specific diseases, such as Guillain–Barré syndrome, and myasthenia gravis. Emerging clinical evidence supports expanding these treatments to other conditions where autoimmunity is implicated. By integrating immunological insights with clinical trial data, this review offers a comprehensive perspective on how immunotherapies may be tailored to target autoimmune contributors to neuropsychiatric disease. Full article

Recurrent COVID-19, defined as two or more distinct episodes, may reflect an impaired immune response to SARS-CoV-2. In this case–control study, we compared three groups: individuals with recurrent COVID-19, those with a single episode, and SARS-CoV-2-naïve controls. We genotyped six immune-related SNPs, including TLR7 rs179008, and measured CD4⁺ and CD8⁺ T cell responses to SARS-CoV-2 antigens using flow cytometry. The T allele of TLR7 rs179008, previously linked to reduced receptor expression, was significantly overrepresented in the recurrent COVID-19 cohort. At baseline, frequencies of IFN-γ⁺, IL-2⁺, and TNF-α⁺ cells among CD4⁺ and CD8⁺ T cells did not differ between groups. However, stratification by the rs179008 genotype revealed that T allele carriers displayed diminished IFN-γ production in both CD4⁺ and CD8⁺ T cells and reduced IL-2 production in CD4⁺ T cells. Following vaccination, T cell responses were comparable across all genotypes. The T allele of TLR7 rs179008 is associated with recurrent COVID-19 and may contribute to impaired T cell-mediated immunity. Further studies are warranted to elucidate the mechanistic role of TLR7 variation in SARS-CoV-2 reinfection risk. Full article

BK virus (BKV) reactivation is a significant complication in renal transplant recipients, often leading to BK viremia and BK virus-associated nephropathy (BKVAN), which can compromise graft survival. While the routine monitoring of BKV DNA in blood aids in early detection, identifying pre-transplant risk factors remains a challenge. This study investigates the role of pre- and post-transplant anti-BKV IgG levels and human leukocyte antigen (HLA) alleles in predicting BKV reactivation. The hospital-based cross-sectional study was conducted on 38 renal transplant recipients, stratified into viremic, non-viremic, and BKVAN groups. Anti-BKV IgG levels were measured pre-transplant, at viremia onset, and post-viremia using ELISA. BKV DNA was detected via qPCR, and HLA typing was performed using sequence-specific oligonucleotide probe (SSOP) hybridization. Statistical analyses included Kaplan–Meier survival curves and Cox regression models. Pre-transplant anti-BKV IgG seropositivity was higher in viremic (94%) and BKVAN (100%) patients than in non-viremic recipients (66.6%). Post-transplant IgG levels increased significantly in viremic recipients (p < 0.05). HLA-B44 and HLA-DR15 were significantly associated with increased BKV viremia risk (p = 0.02 and p = 0.01, respectively). Pre-transplant anti-BKV IgG levels and specific HLA alleles influence BKV reactivation risk. These findings highlight the potential for integrating serological and genetic screening into pre-transplant assessments to improve risk stratification and post-transplant monitoring strategies. Full article

Disruption in macrophage polarization is linked to inflammatory diseases and metabolic disorders. Our study aimed to investigate how AHR activation by I3C and TCDD could impact glucose transporters and macrophage phenotypes and functions in human macrophages. Human monocyte-derived macrophages (hMDMs) and THP-1 cell-derived macrophage-like cells were treated for 24 h with 100 ng/mL LPS, 100 nM TCDD, and 10 ng/µL I3C. CYP1A1 and CYP1B1 expression was significantly increased in the I3C and TCDD treatments, with CYP1B1 showing a higher fold change in I3C compared to TCDD. The AHRR expression was the highest in the TCDD group. For macrophage polarization, I3C significantly elevated CD163 expression while reducing CD16 and CD86, indicative of M2-like polarization. Additionally, I3C promoted ARG1 expression and reduced NOS2 levels, while TCDD increased NOS2. A cytokine analysis revealed I3C-induced upregulation of IL-10 and TGF-β, while TCDD significantly elevated TNF-α and IL-12. I3C upregulated glucose transporter genes (GLUT1, GLUT3, GLUT6), in contrast to the downregulation observed in TCDD-treated cells. Our findings demonstrated that I3C distinctly modulates AHR activation genes, macrophage polarization, cytokine expression, and glucose transporter levels in THP-1 cells compared to the TCDD and LPS treatments. Our findings suggest that I3C favors an anti-inflammatory M2-like macrophage polarization coupled with enhanced metabolic activity. Full article

Aims: Patients with Turner syndrome (TS) may have a higher risk of psoriasis as suggested by some reports. Data on this association are still limited. We investigated the association between TS and the risk of prevalent and incident psoriasis by combining results from available studies using systematic reviews and meta-analysis techniques. Methods: Potentially eligible studies were identified from Medline and EMBASE databases from inception to December 2023 using a search strategy that comprised of terms for “Turner syndrome” and “psoriasis”. An eligible cohort study must comprise of two groups of participants—those with and without TS. It must report our outcome of interest—incidence and/or prevalence of psoriasis in each group. The pooled effect estimates were generated using the generic inverse variance method, which assigns weight to each study in reversal to its variance. Meta-analyses of the prevalent and incident psoriasis were conducted separately. Results: A total of 4919 articles were retrieved. After two rounds of independent review by two investigators, five cohort studies (two incident studies and three prevalent studies) met the eligibility criteria and were included in the meta-analyses. The meta-analyses found a significantly elevated risk of both incident and prevalent psoriasis in patients with TS compared to individuals without TS, with the pooled risk ratio of 5.58 (95% CI, 3.73–8.35; I² 0%) and 5.66 (95% CI, 1.52–21.03; I² 19%), respectively. Conclusions: An increased risk of both incident and prevalent psoriasis among patients with TS was demonstrated in this study. Full article

Chronic obstructive pulmonary disease (COPD) is a chronic, debilitating condition that affects the lungs and airways. It is characterized by persistent bronchitis, a condition exemplified by the inflammation of the bronchial tubes, the hypersecretion of mucus, emphysema, and the destruction of the airway parenchyma. The combination of these conditions leads to persistent tissue damage, pulmonary fibrosis, and ongoing inflammation of the airways. The inflammatory response in COPD is a complex process that is orchestrated by a wide range of immune cells. These include lung epithelial cells, monocytes, macrophages, neutrophils, eosinophils, and T and B lymphocytes, among others. These cells work together to produce a wide range of inflammatory biomarkers that are involved in the pathogenesis of COPD. Some of the key inflammatory biomarkers that have been identified in COPD include a variety of cytokines, the C-reactive protein/serum albumin ratio, fibrinogen, soluble receptor for advanced glycation endproducts, club/clara cells in the lungs with a molecular weight of 16 kDa, surfactant protein D, adiponectin, reactive oxygen species, and proteases. This review aims to provide a comprehensive overview of the role of immune cells and key inflammatory biomarkers in the development and progression of COPD. It will delve into the intricacies of the inflammatory response in COPD, exploring the various cell types and biomarkers that are involved in this process. By understanding the underlying mechanisms that drive COPD, we can better develop targeted treatments that can help to alleviate the symptoms of COPD. Full article

Hepatitis B virus (HBV) infection is a major public health risk. Despite the introduction of successful vaccines, which are normally single adjuvanted, there are still some drawbacks, including non-responsiveness in certain groups, short durability of immunity, inadequate protection, and the need for additional doses to be addressed. This study aimed to develop an optimized combination of Cytosine-phosphate-Guanine Oligonucleotides (CPG-ODN2395, CPG-ODN-18281-2 23 mer) and calcium phosphate, and to assess its immunogenicity and toxicity when co-administrated with the commercial HBV vaccine (BEVAC, containing aluminum hydroxide) and an in-house aluminum hydroxide-adjuvanted HBs purified antigen in Balb/c mice. Tail blood was collected from vaccinated Balb/c mice on days 14 and 28 post-immunization to determine the antibody secretion level using an enzyme-linked immunosorbent assay (ELISA). The Tumor Necrosis Factor (TNF-a) and interleukin-6 (IL-6) cytokine expression levels were assessed through real-time PCR, and the safety profile was checked through biochemical and hematological analysis. Our results showed that the combination of CPG-ODN2395, CPG-ODN 18281-2 23 mer, and CAP significantly enhanced the IgG antibody secretion level (p < 0.0001), which also showed a significant increase in IL-6 expression (p < 0.0001). The safety evaluations revealed no adverse impact on liver and kidney function, with normal ALT, AST, urea, and creatinine levels (p < 0.55). Hematological assessments revealed stable parameters across all groups. This study concludes that combining CpG ODNs and calcium phosphate adjuvants with hepatitis B vaccinations has the potential to enhance a stronger immunological response to hepatitis B infection than single adjuvants. These results highlight the promise of this innovative adjuvant system, necessitating more research in clinical environments to increase vaccine effectiveness and sustained protection against HBV. Full article

Type 2 diabetes mellitus (T2DM) is a chronic and progressive dysmetabolic condition related to several complications, including cardiovascular disease, whose incidence is increasing worldwide. Sodium–glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) are two new molecules recently made available for T2DM treatment, with the aim of reducing hyperglycemia. Recent evidence has also highlighted that in addition to the glucose-lowering action, both SGLT2i and GLP1-RAs ensure significant beneficial effects in reducing cardiovascular damage in T2DM patients. Interestingly, these benefits cannot be exclusively attributed to the improved glycemic control. Indeed, experimental and clinical studies have shed light on the protective role of SGLT2i and GLP-1RAs against inflammation and oxidative stress, especially in the heart and vasculature. In our review we elucidate the potential cardiovascular benefits provided by SGLT2i and GLP1-RAs to T2DM subjects by exploring the molecular pathways involved in the process of cardiovascular protection. Full article

Hematopoietic stem cell transplantation is one of the most intricate immune therapies used for patients with hematological diseases or immune disorders. In addition to the inherent immunosuppression from their primary condition, many of these patients usually receive cytotoxic chemotherapy, radiation therapy, broad-spectrum antibiotics, or experience extended nutritional perturbations. These factors collectively lead to inflammation and the disruption of gut microbiota. Additionally, about 40–60% of patients undergoing fully HLA-matched allogeneic transplantation are expected to develop acute graft-versus-host disease (aGVHD), even with prophylactic measures such as calcineurin inhibitors, methotrexate/mycophenolate, or post-transplant cyclophosphamide treatment. Recent research has elucidated the complex interplay between immune effectors in the gastrointestinal tract and microbial populations within a proinflammatory peri-transplant environment, revealing its significant effect on survival and post-transplant complications such as aGVHD. This review will explore the relationship between dysbiosis during allogeneic transplantation and mechanisms that can help clarify the link between gut microbiota and the risk of GVHD, along with emerging therapeutic strategies aimed at addressing dysbiosis during hematopoietic stem cell transplantation. Full article

The immune system’s ability to detect and eliminate transformed cells is a critical factor in suppressing cancer development. However, immune surveillance in tumors is often disrupted by various immune escape mechanisms, many of which remain poorly understood. The Natural Killer Group 2D (NKG2D) receptor is an activating receptor expressed on natural killer (NK) cells and cytotoxic T lymphocytes. It can recognize and bind with varying affinities to a wide range of structurally diverse ligands, including MHC class I chain-related proteins A and B (MICA and MICB) and members of the ULBP family (ULBP1-6). The expression of these ligands plays a crucial role in immune antitumor responses and cancer immunoevasion mechanisms. Some evidence suggests that functional polymorphisms in the NKG2D receptor and the genes encoding its ligands significantly influence HLA-independent cancer immunosurveillance. Consequently, the NKG2D-NKG2D ligands (NKG2DLs) axis represents a promising target for developing novel therapeutic strategies. This review aims to provide a general overview of the role of NKG2D and its ligands in various malignancies and explore their potential in advancing personalized cancer treatment protocols. Full article

NK cells have traditionally been classified as effectors of innate immunity, even though they also exhibit some features of adaptive immunity such as memory. NK cells contribute to the lysis and growth inhibition of cancer, mediating direct cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) and regulating the functions of other immune cells, respectively. NK cells regulate the function of other immune cells via the release of inflammatory cytokines and chemokines. Currently, NK cell therapeutics in oral cancer have been less efficient due to several limitations, as follows: (a) lower percentages of NK cells in peripheral blood immune cells; (b) limited survival and decreased function of NK cells, especially in the tumor microenvironment; and (c) a lack of tools or methodologies to expand and activate NK cells to the levels that are required for the effective targeting of oral cancer. To overcome these limitations, we established and demonstrated a novel technology for activating and expanding highly functional NK cells coined as supercharged NK (sNK) cells. This review summarizes the characteristics of sNK cells and highlights their superior anti-cancer activity when compared to primary activated NK cells. Full article

T cell phenotypes and kinetics are emerging as crucial factors associated with immunotherapeutic responses in a wide range of solid cancer types. However, challenges remain in understanding the spatial and temporal profiles of T cells with differential phenotypes due to difficulties in single-cell analysis with preserved tissue structures. Here, we provide an optimized 12-marker multiplex immunohistochemical (IHC) panel and single-cell-based quantitative assessment to identify the spatial distributions of T cell phenotypes in formalin-fixed paraffin-embedded sections. This panel revealed differential T cell populations with spatial localizations in human tonsil tissue, where the percentages of CD8⁺ T cell-expressing programmed death receptor-1 (PD-1), T cell immunoglobulin and mucin domain 3 (TIM3), and other T cell phenotypic markers vary by tonsillar tissue components such as follicles, parenchyma, and epithelium. A specimen from salivary gland adenocarcinoma during hyper-progression, followed by anti-PD-1 treatment, exhibited the exclusion of CD8⁺ T cells from the intratumoral regions. Although the vast majority of peritumoral CD8⁺ T cells exhibited proliferative effector T cell phenotypes with PD-1⁻TIM3⁻Ki67⁺CD45RA⁺, intratumoral CD8⁺ T cells showed exhausted phenotypes with PD-1⁺TIM3⁻ and increased Eomes expression, which might be related to poor therapeutic response in this case. To verify these findings in the context of temporal changes, we analyzed six longitudinal samples from a single patient with maxillary sinus cancer, observing increased T cell exhaustion along with metastasis and progression. Together, highly multiplexed IHC can be applied to analyze the spatiotemporal phenotypes of T cells, potentially contributing to the understanding of the mechanisms of resistance to immunotherapy. Full article

Systemic autoimmune diseases (SAIDs) affect millions worldwide, presenting significant clinical challenges due to their complex pathogenesis and limited treatment options. Traditional immunosuppressive therapies, while effective, often lack precision, leading to significant side effects and inadequate disease control. Recent advances in synthetic immunology offer promising avenues for precise, targeted interventions in SAIDs. This review examines the latest innovations in synthetic immunology for treating autoimmune diseases, focusing on engineered immune cells, synthetic biologics, and gene-editing technologies. It explores the therapeutic potential of these approaches to modulate immune tolerance, reduce systemic inflammation, and enhance patient-specific treatment efficacy. However, despite these promising developments, challenges remain, including immune system complexity, safety concerns, and regulatory hurdles that may hinder clinical translation. This review aims to consolidate current advancements, address existing barriers, and outline potential future directions for synthetic immunology in autoimmune disease management, highlighting synthetic immunology’s role in transforming the therapeutic landscape for SAIDs. Full article