The Burden of Non-Infectious Organ-Specific Immunopathology in Pediatric Common Variable ImmunodeficiencySzczawińska-Popłonyk, Bekalarska, Jęch
et alInt J Mol Sci (2025) 26 (6)
Abstract: The pediatric common variable immunodeficiency (CVID) is the most frequent symptomatic antibody production defect characterized by infectious and non-infectious autoimmune, inflammatory, and lymphoproliferative complications. The background for CVID-related organ-specific immunopathology is associated with immune dysregulation and immunophenotypic biomarkers with expansion of CD21low B cells, and dysfunctional memory B cell, follicular T cell, and regulatory T cell compartments. The ever-increasing progress in immunogenetics shows the heterogeneity of genetic background for CVID related to the complexity of clinical phenotypes. Multiple systemic modulatory pathways are determined by variants in such genes as TACI or TNFRSF13B gene encoding for BAFF-R, CTLA-4, LRBA, NFKB1 and NFKB2, and PIK3CD or PIK3R1. The organ-specific immunopathology encompasses a spectrum of disorders associated with immune dysregulation, such as granulomatous interstitial lung disease, hepatocellular nodular regenerative hyperplasia, enteropathy, neuropathy, endocrinopathies, and dermatoses. This review is aimed to define and delineate the organ-specific immunopathology in pediatric CVID. It is also conducted to gather data facilitating a better understanding of complex and heterogeneous immunophenotypes in the context of immune dysregulation mechanisms and genetic background determining manifestations of the disease and implicating personalized targeted therapies with biological agents.
Genetic drivers and clinical consequences of mosaic chromosomal alterations in 1 million individualsZhao, Pershad, Poisner
et almedRxiv (2025)
Abstract: Mosaic chromosomal alterations of the autosomes (aut-mCAs) are large structural somatic mutations which cause clonal hematopoiesis and increase cancer risk. Here, we detected aut-mCAs in 1,011,269 participants across four biobanks. Through integrative analysis of the minimum critical region and inherited genetic variation, we found that proto-oncogenes exclusively drive chromosomal gains, tumor suppressors drive losses, and copy-neutral events can be driven by either. We identified three novel inherited risk loci in CHI3L2, HLA class II, and TERT that modulate aut-mCA risk and ten novel aut-mCA-specific loci. We found specific aut-mCAs are associated with cardiovascular, cerebrovascular, or kidney disease incidence. High-risk aut-mCAs were associated with elevated plasma protein levels of therapeutically actionable targets: NPM1, PARP1, and TACI. Participants with multiple high-risk features such as high clonal fraction, more than one aut-mCA, and abnormal red cell morphology had a 50% cumulative incidence of blood count abnormalities over 2 years. Leveraging inherited variation, we causally established aut-mCAs as premalignant lesions for chronic lymphocytic leukemia. Together, our findings provide a framework integrating somatic mosaicism, germline genetics, and clinical phenotypes to identify individuals who could benefit from preventative interventions.
Caregiver Contribution to Self-Care of Chronic Illness Inventory: Evaluation of Measurement Properties in a Middle-Income CountryAdëraj, Arapi, Mazzotta
et alNurs Rep (2025) 15 (2)
Abstract: Background/Objectives: Caregivers engage in essential tasks that support patients' well-being and survival, including administering medications, promoting healthy lifestyle choices, and monitoring and managing symptoms. To date, no valid and reliable instrument is available to assess Caregiver Contribution (CC) to self-care in chronic conditions in middle-income countries such as Albania. Aim: To evaluate the measurement properties (structural and construct validity, internal consistency reliability, stability, and measurement error) of the instrument CC to Self-Care of the Chronic Illness Inventory (CC-SC-CII) in Albanian caregivers caring for elderly people affected by multiple chronic conditions. Methods: A cross-sectional study. We enrolled caregivers of patients with multiple chronic conditions, from August 2020 to April 2021, if they were (a) 18 years of age or older and (b) were identified by the patient as the main unpaid caregiver. Results: Confirmatory factor analysis confirmed the two-factor structure of the CC to Self-Care Maintenance and Management scales and the one-factor structure of the CC to Self-Care Monitoring scale. Reliability estimates were adequate for all (coefficients ranging between 0.827 and 0.961). The construct's validity was supported. The measurement error was adequate. Conclusions: The Albanian version of the CC to Self-Care of the Chronic Illness Inventory features sound measurement properties and is a valid and reliable instrument for assessing caregiver contribution to patient self-care behaviors in the Albanian population.
Telitacicept for systemic lupus erythematosus with post‑surgical papillary thyroid carcinoma: A case reportTan, Huang, Tan
et alBiomed Rep (2025) 22 (3), 48
Abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex etiology primarily linked to abnormalities in B lymphocytes within the human body, resulting in the production of numerous pathogenic autoantibodies. Telitacicept is a relatively novel humanized, recombinant transmembrane activator, calcium modulator and cyclophilin ligand interactor fused with the Fc portion (TACI-Fc). It works by competitively inhibiting the TACI site, neutralizing the activity of B-cell lymphocyte stimulator and A proliferation-inducing ligand. This, in turn, inhibits the development and survival of plasma cells and mature B cells. A 28-year-old female was admitted to the Department of Rheumatology and Immunology (People's Hospital of Longhua; Shenzhen, China) in June 2021 due to systemic edema for more than a month and hair loss lasting for a week. After comprehensive examination, the patient was diagnosed with SLE with hematological system involvement, serositis, lupus nephritis and secondary antiphospholipid syndrome. After receiving medications including glucocorticoids, mycophenolate mofetil and cyclosporine, the patient's white blood cells, platelets, hemoglobin, urinary protein and multiple serositis returned to normal. However, the levels of complement 3 (C3) and C4 did not significantly improve. Subsequently, the patient underwent thyroid ultrasound examination, which suggested thyroid nodules. After thyroid puncture biopsy, the patient was diagnosed with papillary thyroid carcinoma (PTC). After surgical resection, the patient was confirmed to have PTC by pathological biopsy, with no lymph node metastasis. At two months after surgery, the patient was treated with telitacicept, and the complement levels not only returned to normal but also remained stable for a long time. The present case was the first to report the use of telitacicept for the successful treatment of a patient with SLE with post-surgical PTC, providing a potential therapeutic option for SLE with a prior history of carcinoma. The role of telitacept in this field requires further research and attention.Copyright: © 2025 Tan et al.
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