Advanced glycation end-products (AGEs) are a variety of endogenous and exogenous substances that play an important role in inflammation, allergies, and autoimmune diseases. AGEs’ pathogenicity, alongside advanced oxidation protein products (AOPPs) and other ligands, lies in their ability to bind the receptor for advanced glycation end-products (RAGE) and trigger pro-inflammatory signaling pathways and cytokine release. The literature reports numerous studies on the role of the AGE-RAGE axis in various allergic conditions, including bronchial asthma, atopic dermatitis, food allergies, and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, or Hashimoto’s thyroiditis, where the significant role of the AGE–RAGE axis in the immunopathogenesis of both allergic and autoimmune conditions is largely discussed and demonstrated. They suggest promising opportunities for the development of new diagnostic markers and targeted therapeutic strategies. However, further large-scale studies are needed to fully understand this multifaceted pathway and translate these insights into effective clinical interventions.

The skin is a complex immunological organ in which reactive oxygen species (ROS)-related pathways and host–microbe interactions synergically maintain immune homeostasis. Dysregulation of several oxidative mechanisms, including lipid peroxidation, mitochondrial dysfunction, ferroptosis, and impaired antioxidant defenses, alongside gut microbiome imbalance, is increasingly recognized as a key modulator of the immune response involved in disease onset and progression. However, their role in immune-mediated dermatoses remains incompletely defined. This narrative review aims to provide a comprehensive overview of the contribution of these altered pathways to the pathogenesis and prognosis of the major immune-mediated skin diseases. Across all conditions examined, elevated oxidative biomarkers, such as malondialdehyde (MDA), advanced glycation end-products (AGEs), advanced oxidation protein products (AOPPs), 8-hydroxydeoxyguanosine (8-OHdG), and reduced antioxidant capacity are consistently reported. Ferroptosis, driven by iron-dependent lipid peroxidation and dysfunction of Glutathione peroxidase 4 (GPX4), emerges as a relevant cell death pathway, particularly in psoriasis and atopic dermatitis (AD). In parallel, dysbiosis of the gut and skin microbiomes, characterized by depletion of short-chain fatty acid (SCFA)-producing taxa such as Faecalibacterium prausnitzii, Bifidobacterium, and Akkermansia muciniphila, has been reported across multiple diseases. Particular attention is given to shared molecular axes, such as the disruption of epithelial barrier integrity, activation of innate and adaptive immune responses, and the role of microbial-derived metabolites in modulating redox signaling, unraveling a bidirectional crosstalk. Emerging therapeutic strategies targeting these bidirectional crosstalks show biological plausibility and promising preliminary results. Integrating redox and microbial profiling into clinical practice may improve patient stratification and foster the development of more personalized therapeutic approaches beyond conventional immunological treatments.

Vitamin D is a fat-soluble hormone essential for bone mineralization. In addition to this role, vitamin D is known for its immunomodulatory effects through its binding to intracellular vitamin D receptors (VDRs), which translocate to the nucleus of immune cells, including antigen-presenting cells (APC), B lymphocytes, T lymphocytes and monocytes, thereby modulating the transcription of genes responsible for the immune response. Vitamin D deficiency is associated with an increased risk of developing infections and autoimmune diseases. The purpose of this review is to evaluate vitamin D deficiency in patients with primary immunodeficiency (CVID, XLA, DGS, APECED, SCID, WAS, HIES), to assess its clinical and therapeutic impact. Vitamin D deficiency, often asymptomatic, is associated with more severe clinical conditions in subjects with PID. It can be associated with osteoporosis, fractures, myelofibrosis and endocrine disorders such as hypocalcemia. These patients responded beneficially to calcitriol therapy, underscoring the need for long-term monitoring.

Sensitization to non-specific lipid transfer proteins (nsLTPs) is highly prevalent in Mediterranean countries. Pru p 3 from peach is a major allergen responsible for IgE-mediated food allergies. As a panallergen, Pru p 3 shows high sequence homology with nsLTPs from other Rosaceae fruits but also from botanically unrelated sources, including nuts and pollens, leading to extensive cross-reactivity complicating diagnosis and management. Given the worldwide prevalence of peanut and tree nut allergies, this study aimed to investigate sensitization patterns in Pru p 3-sensitized patients with tree nut allergy, using artificial intelligence (AI) to identify predictors of clinical reactivity and severity. Data from Pru p 3–sensitized patients with symptoms to peach and/or nuts were analyzed. Sensitization profiles were modeled using an XGBoost algorithm to explore associations with symptoms and severity. Patients sensitized to Pru p 3 and symptomatic for peach and nuts showed predominant sensitization to peanut and hazelnut, but AI revealed stronger associations between clinical reactivity and sensitization to hazelnut, walnut, and almond. Among patients with nut allergy and peach-asymptomatic, peanut and hazelnut sensitization were most frequent, while peach-symptomatic ones, walnut and almond sensitization predominated. Overall, walnut sensitization emerged as the main predictor of clinical severity and increasing number of sensitizations correlated with higher severity. The XGBoost algorithm identified specific allergen combinations associated with symptoms and severity, highlighting walnut sensitization as the strongest severity predictor. Machine learning approaches represent a promising tool for refining risk stratification and personalizing management in nsLTP-related food allergy.