Research

Allergol Immunopathol (Madr). 2026 Jan 1;54(1):87-95. doi: 10.15586/aei.v54i1.1465. eCollection 2026.

ABSTRACT

BACKGROUND: Primary immunodeficiency diseases (PIDs) are an expanding group of rarely observed immune system disorders. Various clinical conditions, such as autoimmunity, immune dysregulation, and inflammation, could affect multiple organ systems in PID patients. The heart may be one of these organs; however, studies on this topic are rare. Atrial fibrillation (AF) is a significant cause of mortality and morbidity in the community and an increased P-wave dispersion (PWD) and atrial electromechanical delay (AED) are well-known markers indicating a predisposition to AF. We aimed to determine whether AED and/or increased PWD predict the early risk of AF in PID patients.

METHODS: This single-center, prospective controlled study included 61 PID and 60 control group patients. All participants underwent resting electrocardiography, echocardiography, and atrial electromechanical conduction time (AECT) monitoring using tissue Doppler imaging evaluated by an experienced cardiologist.

RESULTS: The PID group had a statistically significantly higher Pmax, Pmin, and PWD values, compared to the control group (102 [92-108] vs. 88 [82-99] ms, P < 0.001; 74 [70-80] vs. 68 [62-72] ms, P < 0.001; 26 [22-30] vs. 21 [18-26] ms, P = 0.001, respectively). Right atrial delay and interatrial delay were discovered to be statistically significantly higher in PID group (4 [2-6] vs. 2 [2-4] ms, P < 0.001; 6 [4-8] vs. 4 [4-6] ms, P = 0.039, respectively). Left atrial delay was also discovered to be high in the PID group, although this difference was not statistically significant (6 [4-6] vs. 4 [3-6] ms; P = 0.05).

CONCLUSION: We demonstrated that the well-known predictors of AF, AECT, and PWD were increased in PID patients. This result aids in the follow up and survival of PID patients, who experience multiple complications, by enabling the early identification of AF-related mortality and morbidity risk.

PMID:41510927 | DOI:10.15586/aei.v54i1.1465

Medicine (Baltimore). 2026 Jan 2;105(1):e46420. doi: 10.1097/MD.0000000000046420.

ABSTRACT

RATIONALE: Griscelli syndrome (GS) is a rare autosomal recessive disorder marked by partial oculocutaneous albinism, immunodeficiency, and neurological issues. It has 3 types based on genetic mutations. This report focuses on a patient with GS type 2, characterized by immune abnormalities and neurological symptoms, with only 160 cases documented globally.

PATIENT CONCERNS: A 1-year-old boy presented with hyperthermia, diarrhea, and vomiting, revealing hypopigmented skin and silvery-gray hair. He exhibited tachycardia, abdominal distension, hepatosplenomegaly, and signs of immunocompromise. Neurologically, he showed developmental delays and hyperreflexia. Lab tests indicated anemia, thrombocytopenia, and elevated triglycerides.

DIAGNOSES: Based on clinical history and laboratory tests diagnosed with GS type 2.

INTERVENTIONS AND OUTCOMES: The patient received symptomatic treatment, antibiotics, and frequent transfusions, with strict infection prevention due to limited resources for stem cell transplantation.

LESSONS: GS, identified in 1978, is a rare autosomal recessive disorder marked by partial albinism and immunodeficiency, with around 160 cases primarily from the Mediterranean. It comprises 3 types: GS1, GS2, and GS3, each with unique genetic and clinical features. GS1 exhibits partial albinism and neurological issues without immune effects due to MYO5A mutations. GS2 presents severe immunodeficiency and risks such as hemophagocytic lymphohistiocytosis linked to RAB27A mutations. GS3, caused by melanophilin gene mutations, has a better prognosis. Diagnosis involves hair microscopy and genetic testing, and while supportive treatments exist, early diagnosis is vital for improved outcomes. GS is a rare genetic disorder with varied symptoms, categorized into 3 types, requiring genetic testing for diagnosis and treatment ranging from management to stem cell transplantation.

PMID:41496009 | DOI:10.1097/MD.0000000000046420

J Orthop. 2025 Dec 12;73:177-183. doi: 10.1016/j.jor.2025.12.023. eCollection 2026 Mar.

ABSTRACT

INTRODUCTION: Total hip (THA) and knee arthroplasty (TKA) are widely successful procedures but remain susceptible to complications. Patients with primary immunodeficiency (PI) conditions may face increased postoperative risks, though data is limited. This study evaluated postoperative outcomes after THA and TKA in PI patients, hypothesizing higher complication rates compared with matched controls.

METHODS: A retrospective cohort study was conducted using the PearlDiver Mariner database (2010-2020). Patients undergoing primary THA or TKA were identified by CPT codes and matched 1:1 by age, sex, and Charlson Comorbidity Index, obesity, tobacco use, alcohol abuse, and osteoarthritis. Patients with PI conditions were identified with a comprehensive list of International Classification of Diseases (ICD) 9/10 codes. Postoperative complications were assessed at 90 days, 1 year, and 2 years. Multivariable logistic regression was used to identify independent associations with PI status.

RESULTS: After 1:1 matching, PI patients had significantly higher 90-day postoperative incidence of deep vein thrombosis (DVT), pneumonia, urinary tract infection (UTI), and any complication following THA. At 1 year, PI patients were found to have increased odds of periprosthetic joint infection (PJI), DVT, acute kidney injury (AKI), pneumonia, UTI, and any complication. 2 years postoperatively, PI was associated with increased odds of PJI revision. Within 90 days of TKA, PI patients displayed a higher incidence of surgical site infection (SSI), AKI, wound disruption, pneumonia, UTI, readmission, and any complication. After one year, PI patients had higher rates of PJI, SSI, DVT, AKI, wound disruption, pneumonia, UTI, readmission, and any complication. At 2 years follow up, there were no significant differences between groups.

CONCLUSIONS: In patients undergoing THA and TKA, PI was associated with significantly higher odds of infectious and medical complications, despite lower overall rates of metabolic comorbidities. These findings highlight the need for PI-specific perioperative protocols to improve both clinical outcomes and economic benefits.

PMID:41497825 | PMC:PMC12767844 | DOI:10.1016/j.jor.2025.12.023

J Paediatr Child Health. 2026 Jan 7. doi: 10.1111/jpc.70280. Online ahead of print.

ABSTRACT

AIM: To evaluate the diagnostic yield and clinical triage performance of a structured, multistep algorithm in children referred for suspected inborn errors of immunity (IEI) due to recurrent infections.

METHODS: This single-centre study included 705 children (0-18 years) referred for recurrent infections. All were screened using JMF and/or MENA criteria. Of these, 132 met at least one criterion and underwent stepwise immunologic evaluation, including advanced testing when indicated.

RESULTS: Of 705 children referred with recurrent infections, 132 (18.7%) met screening criteria and underwent structured immunologic evaluation. Inborn errors of immunity were diagnosed in 50 patients (7.1%), with a 71% diagnostic confirmation rate. Pathogenic variants were detected in 74%, immunoglobulin abnormalities in 78% and all showed lymphocyte subset disturbances. The most common classifications were antibody deficiencies (32%) and syndromic combined immunodeficiencies (28%). Half received intravenous immunoglobulin, and no mortality occurred during follow-up.

CONCLUSION: The structured diagnostic algorithm based on JMF and MENA criteria improved IEI diagnosis and enabled effective prioritisation of children presenting with non-infectious immune phenotypes. This model reduced unnecessary testing, supported efficient allocation of limited resources and facilitated timely diagnosis. The approach offers a practical, cost-effective solution particularly applicable in regions with high consanguinity rates and limited access to advanced immunologic diagnostics.

PMID:41498369 | DOI:10.1111/jpc.70280

J Clin Immunol. 2026 Jan 6. doi: 10.1007/s10875-025-01972-1. Online ahead of print.

ABSTRACT

Patient-reported outcomes are critical to multidisciplinary, patient-centred approaches in diseases requiring lifelong management. Among inborn errors of immunity (IEIs), reports on this subject are typically limited to specific diagnostic subgroups or focus narrowly on the route of immunoglobulin replacement therapy (IgRT), offering a restricted perspective. We aimed to evaluate the health-related quality of life (HRQoL) and IgRT-related treatment satisfaction (TS) of a heterogeneous cohort of IEI patients and identify factors influencing these outcomes to guide improving the health and well-being of IEI patients. We conducted a cross-sectional survey targeting IEI patients on IgRT, assessing TS (TSQM-9) and HRQoL (KINDL/SF-36). Patient/caregiver-reported data were integrated with clinical data to identify outcomes and influencing factors. The survey included 500 IEI patients (356 children, 144 adults) diagnosed 54% Primary Antibody Deficiency (PAD), 36% combined immunodeficiency, 7% immune-dysregulation, and 3% other IEIs. Non-PAD diagnoses, comorbidities, absence of school/work attendance, and IgRT-related systemic adverse reactions negatively impacted HRQoL. Severe infections and related hospitalizations adversely influenced both HRQoL and TS. The subcutaneous route of IgRT, particularly at home, was associated with higher TS due to its convenience and reduced school/work absenteeism. However, the IgRT route did not influence adult HRQoL. Patient-reported well-being and satisfaction in IEIs are multifactorial and cannot be solely attributed to the route of IgRT. Minimizing negative experiences related to the disease or its treatment and, where possible, encouraging patients to maintain school/work attendance or engage in activities that promote societal participation can enhance self-esteem, coping abilities, and overall well-being.

PMID:41493669 | DOI:10.1007/s10875-025-01972-1

Pharmazie. 2025 Dec 1;80(11):156-160. doi: 10.1691/ph.2025.5665.

ABSTRACT

Since many years, immunoglobulin G (IgG) substitution has been used to treat patients with primary immunodeficiencies (PID) to reduce the number of infections and the burden of disease. Nevertheless, many patients continue to suffer from persisting infections. In this SINUS study, a patient questionnaire consisting of 21 questions was used to assess the current situation in patients with PID. Of the 160 patients included, most showed a persistent tendency to infections (N=140, 87.5%). During the last 12 month, most of the patients suffered from upper and lower respiratory tract infections such as sinusitis (N=85, 60.7%), bronchitis (N=88, 62.9%), and pneumonia (N=10, 7.1%). Yet the presence of persistent infections was not inversely correlated with patient satisfaction. Therefore, the treating physicians need to carefully evaluate the infection history and additional therapeutic approaches are required for satisfying improvement in the patient’s infection control. Patients are open to explore new ways to achieve this goal.

PMID:41491392 | DOI:10.1691/ph.2025.5665

Eur J Med Res. 2026 Jan 5. doi: 10.1186/s40001-025-03709-7. Online ahead of print.

ABSTRACT

BACKGROUND: USP39 is involved in mRNA splicing and stress responses. This study analyzed USP39 expression and its clinical relevance in sepsis, aiming to provide a novel treatment target for sepsis.

METHODS: The RNA-seq datasets were used for analyzing the expression profile and clinical significance of USP39 in both sepsis and control groups. Functional pathway enrichment was performed using GSEA and GSVA with the clusterProfiler package (3.14.3). Immune infiltration was evaluated via single-sample GSEA (ssGSEA). The prognostic value of USP39 was assessed utilizing Cox regression, and its diagnostic performance was determined via receiver operating characteristic (ROC) curve analysis employing the survival (3.5.7) and pROC (1.18.5) packages, respectively. For single-cell RNA-seq (scRNA-seq) data (GSE175453), we performed quality control, normalization, principal component analysis (PCA), batch correction, clustering, and Uniform Manifold Approximation and Projection (UMAP) visualization employing the Seurat 4.4.0 package. THP-1 cells were treated with lipopolysaccharide (LPS) to mimic septic injury. USP39 was overexpressed via pcDNA3.1 transfection. Cellular assays were conducted to measure cell viability, apoptosis, and inflammatory cytokines (IL-1β, IL-6, TNF-α).

RESULTS: Our study found that USP39 was significantly downregulated in sepsis patients and was associated with age, diabetes, and Intensive Care Unit (ICU)-acquired infections. Functional enrichment analysis revealed that high USP39 expression was linked to metabolic processes, primary immunodeficiency, and spliceosome, and immune response and inflammation pathway. In addition, USP39 also exhibited a high diagnostic value and was identified as an independent prognostic marker in sepsis. ssGSEA revealed higher infiltration of CD8⁺ T cells, activated B cells, and CD4⁺ T cells in the high USP39 expression group, while Th17 and NK cells were more abundant in the low USP39 expression group. According to the results of scRNA-seq analysis, USP39 exhibited significant differential expressions in monocytes and T cells, with low expression observed in sepsis. Furthermore, in vitro experiments confirmed that overexpression of USP39 significantly enhanced cell viability and suppressed apoptosis in LPS-induced THP-1 cells while also inhibiting the expression of inflammatory cytokines.

CONCLUSION: The significant downregulation of USP39 was correlated with both clinical features and immune infiltration in sepsis, highlighting its role in immune regulation and its potential as a prognostic biomarker.

PMID:41491968 | DOI:10.1186/s40001-025-03709-7

Front Dent. 2025 Sep 13;22:37. doi: 10.18502/fid.v22i37.19830. eCollection 2025.

ABSTRACT

Myelodysplastic syndrome (MDS) is a bone marrow clonal stem cell disorder characterized by the inability of immature blood cells to mature. Oral squamous cell carcinoma (OSCC) has not been previously reported in MDS patients without underlying diseases. We present a case of poorly differentiated OSCC in a 27-year-old patient with MDS. A literature review revealed 11 case reports about solid tumors in different organs of MDS patients. Among these, 5 articles reported head and neck carcinoma but none of them reported oral cancer in MDS patients. MDS predisposes patients to hematopoietic and non-hematopoietic malignancies. The oral cavity is one of the critical sites that needs to be examined periodically and regularly in MDS patients to detect OSCC in its early stages.

PMID:41492562 | PMC:PMC12765349 | DOI:10.18502/fid.v22i37.19830

Front Immunol. 2025 Dec 17;16:1683892. doi: 10.3389/fimmu.2025.1683892. eCollection 2025.

ABSTRACT

BACKGROUND: Primary immunodeficiencies (PIDs) comprise a heterogeneous group of disorders characterized by defects in the immune system, predisposing patients to recurrent and severe infections. Type 68 immunodeficiency, caused by biallelic pathogenic variants in MYD88, is rare; to date, at least 26 affected individuals have been reported in the literature, several of whom belong to the same families. This condition typically presents in early childhood with recurrent severe bacterial infections (SBIs), often accompanied by an absent or attenuated inflammatory response.

CASE PRESENTATION: We report a 3-month-old male patient admitted with multiple SBIs, including left-sided abscessing pyelonephritis, pyogenic liver abscess, and septic pneumonia complicated by tension pneumothorax. Initial immunological screening revealed normal leukocyte counts, immunoglobulin levels, lymphocyte subpopulations, and TREC (T-cell receptor excision circle)/KREC (kappa-deleting recombination excision circles) copy numbers. Congenital urinary tract anomalies were excluded. Despite clinical improvement, the patient subsequently developed a cold abscess of the cervical lymph node due to Staphylococcus aureus. Whole-exome sequencing identified two novel compound-heterozygous missense variants in MYD88 (p.Leu35Pro and p.Trp47Cys), both located in the death domain. In silico analysis suggested potential disruption of α-helical structure and MyD88-MyD88/IRAK4 interactions. Sanger sequencing confirmed parental heterozygosity, establishing the diagnosis of type 68 immunodeficiency. Prophylactic antibiotic therapy was initiated, and no further SBIs occurred during 8 months of follow-up.

CONCLUSION: This report expands the genetic spectrum of immunodeficiency 68 by identifying novel MYD88 mutations. Our findings highlight the value of genetic testing in severe, recurrent bacterial infections, irrespective of conventional laboratory results, and demonstrate improved outcomes achievable with modern management.

PMID:41479884 | PMC:PMC12754000 | DOI:10.3389/fimmu.2025.1683892

Cureus. 2025 Dec 1;17(12):e98264. doi: 10.7759/cureus.98264. eCollection 2025 Dec.

ABSTRACT

Good’s syndrome (GS) is a primary immunodeficiency characterized by thymoma-associated hypogammaglobulinemia, leading to recurrent infections. A 71-year-old woman, with a history of oral and perineal lichen planus, chronic sinusitis, recurrent otitis, and thymoma excision in 2021, presented with fever and diarrhea after testing positive for SARS-CoV-2. On admission, she appeared stable but had bleeding lichen planus lesions and required supplemental oxygen for moderate respiratory insufficiency. Laboratory results revealed leukocytosis with neutrophil predominance and mild inflammation. A diagnosis of GS was made based on the history of thymoma, detection of hypogammaglobulinemia, and an imbalance in cellular immunity. Additionally, blood cultures grew Campylobacter coli, and she completed a 14-day regimen of azithromycin. After completing the antibiotic course, her respiratory condition worsened with progressive bilateral infiltrates seen on X-ray. The polymerase chain reaction-multiplex respiratory pathogen panel was positive only for SARS-CoV-2. Despite mechanical ventilation, treatment with broad-spectrum antibiotic therapy, and immunoglobulin replacement, her condition continued to deteriorate. The patient’s clinical deterioration was attributed to the combined immunodeficiency from GS and the co-infection of SARS-CoV-2 and C. coli bacteremia. At this point, SARS-CoV-2 remained detectable through the multiplex respiratory panel, and inflammatory markers were elevated, with a C-reactive protein of 21.13 mg/dL, procalcitonin of 0.69 ng/mL, and leukocytosis of 11.7 × 10⁹/L with neutrophilia (10.51 × 10⁹/L). This case emphasizes the risk of severe infections in patients with GS, as well as the importance of early detection and comprehensive management of concurrent bacterial and viral infections in immunocompromised individuals.

PMID:41480435 | PMC:PMC12755914 | DOI:10.7759/cureus.98264