Elena Buti

The link between allergic conditions and common variable immunodeficiency (CVID) is still unclear. Only a few studies suggest allergic diseases are more prevalent in CVID patients than in the general population, and the role of IgE remains poorly defined. This study aims to evaluate the prevalence of allergic conditions in CVID and the role of serum IgE and IgA levels. This prospective, cross‐sectional, case–control study enrolled Italian adult CVID patients to investigate allergic conditions' frequency and relationships between IgE, IgA, and clinical phenotypes. Analyses of diagnostic/prognostic accuracy were performed with ROC curves. We documented an allergic disease in 26.6% of 60 CVID patients, most commonly allergic rhinitis (56.2%) and bronchial asthma (12.5%). CVID patients with allergy had higher IgE levels (+8.9 kU/L, p = 0.006) than non‐allergic ones, but lower than allergic individuals without CVID. IgE deficiency was observed in 65% of CVID patients, with a strong correlation between IgE and IgA levels ( r = 0.7, p < 0.001). Low IgE (< 2.5 kU/L) and IgA levels (< 7 mg/dL) were significantly associated with lymphoproliferative ( p < 0.001) and granulomatous phenotypes ( p = 0.005), achieving an AUC of 94% and 81% for predicting lymphoproliferation and granulomatosis, respectively. The prevalence of allergic conditions in CVID patients is lower compared with previous studies. Low IgE levels served as a good biomarker for CVID and CVID‐phenotypes. Combined serum IgE and IgA assessment improved prognostic stratification.

Intravenous immunoglobulin (IVIg) is a pooled product containing polyclonal IgG collected from the plasma of thousands of healthy donors. Originally developed as a replacement therapy for patients with humoral immunodeficiencies, IVIg has since been widely adopted in the treatment of several autoimmune and inflammatory conditions, owing to its extensive immunomodulatory and anti-inflammatory effects. IVIg exerts a wide range of actions by influencing multiple components of both the innate and adaptive immune systems. These include modulation of Fcγ receptor expression and function, inhibition of complement activation, neutralization of autoantibodies, regulation of cytokine networks, control of pro-inflammatory monocytes, and regulation of multiple immune cells, also through epigenetic modulation. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) represents one of the most complex conditions in pediatric neuropsychiatry, involving the basal ganglia and characterized by a broad range of abrupt-onset neuropsychiatric symptoms, irrespective of the underlying infectious trigger. Recent clinical and translational studies indicate that IVIg can attenuate neuropsychiatric symptoms and restore immune balance in children with PANS. Randomized trials have produced variable results. Converging clinical and mechanistic evidence supports the potential therapeutic value of IVIg in selected patients with moderate-to-severe or relapsing disease. In this overview, we examine current data on IVIg use in PANS, emphasizing its immunological rationale, emerging clinical benefits, and the need for biomarker-guided studies to better identify responders and optimize treatment outcomes.

Autoimmune diseases are heterogeneous, multifactorial disorders defined by a loss of immunological tolerance to self-antigens, resulting in chronic inflammation and tissue damage. Even though the immune system dysregulation most commonly elicits physical symptoms, neuropsychiatric manifestations are frequently observed in autoimmune diseases and are associated with increased morbidity, elevated mortality, and a marked decline in health-related quality of life. Although extensively characterized in systemic lupus erythematosus (SLE) due to its epidemiological relevance and diagnostic complexity, neuropsychiatric involvement holds clinical significance across a wider spectrum of rheumatologic disorders. The frequent co-occurrence of connective tissue disorders with mood and anxiety symptoms suggests shared etiological mechanisms. The early identification of neuropsychiatric manifestations in patients with chronic autoimmune diseases represents the cornerstone of clinical management, given the substantial impact these symptoms have on individuals already burdened by debilitating conditions. We reviewed the principal neuropsychiatric manifestations associated with selected systemic autoimmune diseases: the novelty of this research lies not only in its approach to autoimmune-related neuropsychiatric symptoms but also in the special emphasis placed on the immunopathogenic mechanisms potentially responsible for these manifestations and, more significantly, on therapeutic decision-making, including an evaluation of treatment strategies targeting immune dysregulation and their potential impact on the neuropsychiatric profile, to optimize clinical outcomes and ensure patients have a comprehensive cure.

Background: Common variable immunodeficiency (CVID) is the most frequent symptomatic inborn error of immunity (IEI) in adulthood. Other than recurrent infections, CVID may present with non-infectious complications such as enteropathy, lymphoproliferation, malignancy, and autoimmune diseases. Patients could have a single autoimmune disease (monoautoimmunity) or two or more autoimmune diseases (overt polyautoimmunity). “Latent polyautoimmunity” corresponds to the presence of autoantibodies without a clinically evident autoimmune disease. Methods: The aim of this retrospective study was to describe autoimmunity and polyautoimmunity in a population of 81 CVID adult patients, enrolled from January 2008 to July 2022 (mean follow-up: 8.5 years). Results: We documented at least one autoimmune disorder in 40 patients (49.4%). Moreover, 15 subjects (37.5% of patients with autoimmunity and 18.5% of all CVID population) presented polyautoimmunity. Despite the humoral immune deficiency, we detected different autoantibodies in CVID patients with or without a concomitant autoimmune disease. In both groups with monoautoimmunity and polyautoimmunity, cytopenias were the most common manifestation. Conversely, enteropathy was recorded only in patients with polyautoimmunity (27%, p = 0.006). Patients with polyautoimmunity showed a significantly lower mean age at diagnosis (−12 years, p = 0.018) compared to those with monoautoimmunity. We documented a higher frequency of autoimmunity in CVID patients who had increased diagnostic (+5.6 years) and therapeutic (+7.2 years) delay (p = 0.093 and 0.054, respectively). Conclusions: Polyautoimmunity is a frequent condition in patients affected by CVID. An early start of Ig replacement therapy could help prevent autoimmune complications.