Research

Sci Immunol. 2026 Feb 27;11(116):eadz8360. doi: 10.1126/sciimmunol.adz8360. Epub 2026 Feb 27.

ABSTRACT

The human integrin lymphocyte function-associated antigen 1 (LFA-1; αLβ2) is broadly expressed on leukocytes and involved in various intercellular adhesions. We report complete LFA-1 deficiency because of inherited αL (CD11a) deficiency in otherwise healthy adults of various ancestries with skin lesions due to commensal papillomaviruses. The patients had no history of invasive infections characteristic of children with inherited deficiency of β2 (CD18), which forms heterodimers with αL, αM (CD11b), αX (CD11c), or αD (CD11d). The development and function of leukocyte subsets are largely preserved in the absence of LFA-1. However, the transendothelial migration of skin-tropic cutaneous lymphocyte antigen (CLA)⁺ memory T cells is severely impaired, resulting in their selective sequestration in the blood. Conversely, alternative integrins mediate the extravasation of other leukocytes, including other T cell subsets, to other tissues. Human LFA-1 is required for steady-state T cell homing to the skin and control of papillomaviruses but is otherwise largely redundant. Integrin-mediated T cell compartmentalization is thus essential for organ-selective immune surveillance.

PMID:41758928 | DOI:10.1126/sciimmunol.adz8360

Int Arch Allergy Immunol. 2026 Feb 27:1-26. doi: 10.1159/000551201. Online ahead of print.

ABSTRACT

INTRODUCTION: Primary immunodeficiency diseases (PIDs) are a heterogeneous group of genetic disorders associated with recurrent infections, immune dysregulation, and increased morbidity and mortality when diagnosis is delayed. Primary care physicians (PCPs) play a critical role in early recognition; however, data on PCPs’ knowledge and preparedness regarding PID remain limited. This study aimed to evaluate PCPs’ knowledge, clinical approaches, and preparedness regarding PIDs across Türkiye.

METHODS: This nationwide, cross-sectional study included 385 PCPs-general practitioners (GPs), family medicine residents (FMRs), and family medicine specialists (FMSs)- working in Family Health Centers in Türkiye. Participants completed a structured online questionnaire assessing sociodemographic characteristics, educational background, clinical experience, self-perceived PID knowledge, and performance on 15 PID-related multiple-choice questions based on international guidelines. Total knowledge scores (range: 0-15) were calculated. Correct response rates for individual items and total scores were compared across professional groups and according to educational and clinical variables. Multivariable logistic regression analyses were performed to identify factors independently associated with higher knowledge scores.

RESULTS: The mean total knowledge score was 9.09 ± 2.46 (range 0-15). FMSs significantly higher total scores than FMRs and GPs (GPs 8.67 ± 2.47; FMRs 8.82 ± 2.63; FMSs 9.83 ± 2.03; p < 0.001). In multivariable analysis, being an FMS was independently associated with scoring above the mean (OR = 2.02, 95% CI: 1.26-3.23; p = 0.004). Regular participation in general medical educational activities was associated with significantly higher total scores (9.74 ± 2.31 vs. 8.23 ± 2.38; p < 0.001). PCPs who participated in PID-related educational activities within the past five years were also associated with higher total scores (9.43 ± 2.58 vs. 8.87 ± 2.47; p = 0.027). PCPs who reported requesting immunoglobulin testing or referring patients with recurrent lower respiratory tract infections achieved significantly higher total scores (9.18 ± 2.43 vs. 7.52 ± 2.42; p = 0.001). PCPs who self-perceived their PID knowledge as moderate or good had substantially higher total knowledge scores compared to those who self-perceived their knowledge as low (Low: 8.36 ± 2.55; Moderate: 9.41 ± 2.26; Good: 10.09 ± 2.50; p < 0.001).

CONCLUSION: PID-related knowledge scores among PCPs differed across professional groups, with GPs demonstrating lower scores. Higher knowledge scores were significantly associated with being an FMS and with participation in regular general medical education and past 5 year PID-related education. Strengthening targeted educational strategies, particularly for GPs in primary care settings, may improve early recognition and management of PIDs.

PMID:41758743 | DOI:10.1159/000551201

Biomedicines. 2026 Jan 29;14(2):303. doi: 10.3390/biomedicines14020303.

ABSTRACT

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.

PMID:41751202 | DOI:10.3390/biomedicines14020303

J Clin Med. 2026 Feb 12;15(4):1446. doi: 10.3390/jcm15041446.

ABSTRACT

Background: Common variable immunodeficiency (CVID) is the most frequent symptomatic primary antibody deficiency, associated with recurrent infections, immune dysregulation, and non-infectious complications. Amyloidosis is a rare but severe complication with pulmonary involvement being exceptional. Objective: The aim of this study was to review reported cases of amyloidosis complicating CVID and present a unique case of pulmonary involvement. Methods: A literature research identified observational studies and case reports linking amyloidosis with CVID. Additionally, we describe a patient with CVID complicated by pulmonary and gastrointestinal amyloidosis. Results: Fifteen cases were identified, mostly amyloid A (AA) with multiple organ involvement. Only one case of pulmonary amyloidosis was reported. To date, no cases of pulmonary light-chain amyloidosis (AL) have been described in CVID patients without an underlying plasma cell dyscrasia. Our patient initially presented with AA amyloidosis but evolved to systemic AL type with rapid progression and fatal outcome despite therapy. Conclusions: Amyloidosis should be considered in CVID patients with atypical symptoms. Accurate amyloid typing is essential as treatment differs between AA and AL types. Early recognition may improve outcomes.

PMID:41753134 | DOI:10.3390/jcm15041446

Microorganisms. 2026 Jan 30;14(2):329. doi: 10.3390/microorganisms14020329.

ABSTRACT

Enteroviruses (EVs) are small, non-enveloped RNA viruses that can cause diverse clinical outcomes, particularly severe in patients with primary immunodeficiency (PID) due to their impaired ability to clear infections. This study aimed to characterize EV excretion among 138 Tunisian PID patients over a five-year period, to identify circulating EV serotypes and assess their genetic diversity. A total of 558 stool samples were collected and analyzed by virus isolation and intratypic differentiation using RT-qPCR. Molecular typing was performed through Sanger sequencing of the VP1 region and whole genome sequencing using Next-Generation Sequencing (NGS) technologies. Phylogenetic analysis was conducted using the Maximum Likelihood (ML) method. EVs were detected in 55 stool samples from 23 patients. The excretion kinetics of EVs ranged between 30 and 946 days. Thirteen serotypes were identified, including one Poliovirus (PV) and twelve Non-Polio Enteroviruses (NPEVs), predominantly belonging to species B. Two previously unreported serotypes in Tunisia were detected: Coxsackievirus A5 (CVA5) and Echovirus type 19 (E19). In addition, five patients presented enhanced susceptibility to the excretion of successive EV serotypes, and one patient exhibited a co-infection. A possible recombination event was identified in one patient involving Coxsackievirus B5 (CVB5), Coxsackievirus A9 (CVA9) and Coxsackievirus B1 (CVB1) sequences. Phylogenetic analysis showed close genetic relationships with European, American and Asian strains. These findings underscore the dynamic nature of EV circulation and the importance of ongoing molecular surveillance to detect emerging serotypes and guide public health strategies.

PMID:41753616 | DOI:10.3390/microorganisms14020329

Thorac Res Pract. 2026 Feb 27. doi: 10.4274/ThoracResPract.2026.2025-9-3. Online ahead of print.

ABSTRACT

OBJECTIVE: Non-cystic fibrosis (non-CF) bronchiectasis is a chronic lung disease, primarily characterised by neutrophilic inflammation, with Haemophilus influenzae (HI) frequently isolated from respiratory cultures. Recent adult studies have suggested a potential role for eosinophils in the frequency of pulmonary exacerbations and in lung function decline. This study aimed to evaluate the relationships among peripheral eosinophilia, lower respiratory tract pathogens, age at first pneumonia, and malnutrition in children with non-CF bronchiectasis.

MATERIAL AND METHODS: In this retrospective study, children who were diagnosed with non-CF bronchiectasis were grouped based on nutritional status, eosinophilia, age at first pneumonia, and the most frequently isolated microorganisms. Clinical outcomes were compared across groups.

RESULTS: Among 106 patients (61.3% male), malnutrition was present in 48.1% and eosinophilia in 39.6%. Primary immunodeficiency was the most common etiology (39.6%). HI and Pseudomonas aeruginosa (PA) were isolated in 61.3% and 24.5% of respiratory cultures, respectively. Patients with malnutrition had significantly lower forced expiratory volume in one second and forced vital capacity (FVC) values (P = 0.023 and P = 0.005, respectively). Eosinophilia was more prevalent in patients with PA isolation; was associated with younger ages at first pneumonia and bronchiectasis diagnoses (P = 0.009 and P = 0.017). PA isolation was associated with a higher frequency of aspiration syndromes (P < 0.001) and lower FVC values (P = 0.040). Patients who experienced their first episode of pneumonia before the age of two had more frequent exacerbations and were diagnosed with bronchiectasis at an earlier age.

CONCLUSION: Non-CF bronchiectasis in childhood may be preventable and/or non-progressive when diagnosed early. Clinical features such as malnutrition, eosinophilia, PA isolation, and early-onset pneumonia may help identify children who could benefit from closer clinical monitoring. Further pediatric studies are needed to validate these associations.

PMID:41755496 | DOI:10.4274/ThoracResPract.2026.2025-9-3

Immun Inflamm Dis. 2026 Feb;14(2):e70329. doi: 10.1002/iid3.70329.

ABSTRACT

BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, and recurrent infections. While autoimmune complications are common in WAS, including autoimmune hemolytic anemia, vasculitis, and glomerulonephritis, type 1 diabetes has not been previously described.

CASE PRESENTATION: We report a 37-year-old man with longstanding leukopenia and recurrent infections who was diagnosed with WAS after genetic testing revealed a gain-of-function mutation in the WAS gene. During pre-transplant evaluation for hematopoietic stem cell transplantation, he was incidentally found to have a blood glucose level over 600 mg/dL and an A1c of 12.8%, along with classic symptoms of new-onset diabetes. Antibody testing confirmed autoimmune diabetes with elevated GAD65 and ZnT8 antibodies, and C-peptide of 1.2 ng/mL, with a glucose of 186 mg/dL. He was started on intravenous insulin and later discharged home on a basal-bolus regimen.

CONCLUSION: To our knowledge, this is the first reported case of GAD65 and ZnT8 positive autoimmune diabetes in a patient with WAS. This case expands the spectrum of autoimmune disease associated with WAS and underscores the importance of maintaining a high index of suspicion for atypical autoimmune presentations in patients with WAS.

PMID:41757399 | DOI:10.1002/iid3.70329

J Clin Immunol. 2026 Feb 26. doi: 10.1007/s10875-026-01996-1. Online ahead of print.

NO ABSTRACT

PMID:41748971 | DOI:10.1007/s10875-026-01996-1

Respir Res. 2026 Feb 25. doi: 10.1186/s12931-025-03481-6. Online ahead of print.

NO ABSTRACT

PMID:41742208 | DOI:10.1186/s12931-025-03481-6

Immun Inflamm Dis. 2026 Feb;14(2):e70384. doi: 10.1002/iid3.70384.

ABSTRACT

BACKGROUND: Inborn errors of immunity (IEI), previously referred to as primary immunodeficiencies, are a heterogeneous group of genetic disorders affecting immune development and function. While once considered rare, IEIs are increasingly recognized, particularly in regions with high consanguinity rates. Cutaneous manifestations, as well as ocular and hair abnormalities, may provide early and clinically relevant diagnostic clues. This study aimed to assess the prevalence, types, and diagnostic value of cutaneous, ocular and hair manifestations in patients with IEI.

METHODS: A total of 386 patients with confirmed IEI, classified according to the 2024 IUIS criteria, were retrospectively analyzed. Cutaneous, ocular (e.g., conjunctivitis, keratitis, scleral telangiectasia), and hair manifestations (e.g., alopecia areata, pigmentary abnormalities) were systematically reviewed from medical records. Skin findings were categorized as infectious, immune-allergic (eczema, alopecia areata, urticaria, erythroderma), disease-specific, or other.

RESULTS: Cutaneous, ocular, and/or hair manifestations were identified in 198 patients (51.3%), with 59.1% present at diagnosis. Infectious manifestations were the most common (71.8%), followed by immune-allergic findings (34.8%), including eczema (30.3%), and disease-specific manifestations (17.7%). Ocular findings were observed in 15.7% of patients, while hair abnormalities were present in 4.04%. Skin infections were predominantly bacterial (53.1%) and were most frequent in phagocytic and innate immunity defects. Eczema was most frequent in hyper-IgE syndrome (85.8%), while non-eczematous allergic findings were most common in immune dysregulation. Ocular involvement, including viral retinitis and scleral telangiectasia, and hair abnormalities, such as syndromic hair shaft defects and alopecia areata, were observed across multiple IEI subgroups.

CONCLUSION: Cutaneous, ocular, and hair abnormalities are frequent in IEI and may support early diagnosis. Recognition of recurrent, atypical, or treatment-resistant skin, eye, or hair findings should prompt immunological evaluation, particularly in pediatric patients.

PMID:41738375 | DOI:10.1002/iid3.70384