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J Neuroimmunol. 2025 Jun 7;406:578662. doi: 10.1016/j.jneuroim.2025.578662. Online ahead of print.

ABSTRACT

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disorder that often presents with recurrent infections and autoimmune complications, leading to diagnostic delays. This case report presents two adult male patients, ages 44 and 42, with prolonged histories of recurrent pneumonia, sinusitis, meningitis, and autoimmune encephalitis. Both cases were initially mismanaged due to the isolated treatment of symptoms, delaying the diagnosis of CVID. Comprehensive diagnostic evaluations eventually revealed low immunoglobulin levels, confirming the diagnosis. These cases highlight the importance of early recognition and a multidisciplinary approach to managing patients with recurrent infections and unusual presentations.

PMID:40505342 | DOI:10.1016/j.jneuroim.2025.578662

Sci Rep. 2025 Jun 11;15(1):20042. doi: 10.1038/s41598-025-02472-3.

ABSTRACT

Pulmonary infection is common in connective tissue diseases (CTDs) patients because of immunodeficiency. The basic characteristics of pathogens in this set of patients may differs from immunocompetent patients and largely unclear. We aimed to understand these characteristics by metagenomic next-generation sequencing (mNGS) detection in bronchoalveolar lavage fluid (BALF) from CTDs and explored the primary disease features of this group of patients. Eighty-one CTD patients who were suspected pulmonary infection and received mNGS of BALF as well as conventional microbiologic testing (CMT) were enrolled consecutively. We analysed the types of CTDs, whether accompanied with interstitial lung disease, comparison between performance of mNGS and CMT, and distribution of clinically relevant pathogens, etc. Of the 81 cases, 62 were clinically diagnosed with pulmonary infection. Among all patients, idiopathic inflammatory myopathy accounted for the highest proportion of cases infected, especially anti-MDA5 dermatomyositis and anti-synthetase syndrome. Patients in the pulmonary infection group had been previously treated with higher percentages of anti-rheumatic drugs than those in the non-infection group. The sensitivity of mNGS was higher than that of CMT (80.6% vs. 66.1%). Among the microbes detected by mNGS, the most common bacterial pathogen was Pseudomonas aeruginosa, and the most frequently fungi was Pneumocystis jirovecii. As for the specific pathogens, mNGS had great advantages over CMT in identifying Pneumocystis jirovecii. Idiopathic inflammatory myopathy was the disease most susceptible to pulmonary infections among CTDs. mNGS showed high efficiency for the detection of pathogens that cause pneumonia in BALF from patients with CTDs, especially for Pneumocystis jirovecii.

PMID:40500273 | DOI:10.1038/s41598-025-02472-3

Front Immunol. 2025 May 26;16:1601776. doi: 10.3389/fimmu.2025.1601776. eCollection 2025.

ABSTRACT

STAT3-hyper IgE syndrome (STAT3-HIES) is a primary immunodeficiency disorder caused by dominant-negative mutations in STAT3, leading to defects in Th17 cell differentiation, immune regulation, and tissue repair. Patients are susceptible to recurrent infections and vascular abnormalities, such as vasculopathy and pseudoaneurysms. While involvement of cerebral, bronchial, and coronary arteries has been reported, hepatic artery involvement is rare. We describe a 25-year-old woman with genetically confirmed STAT3-HIES who presented with biliary hemorrhage secondary to a ruptured hepatic pseudoaneurysm. Emergency transcatheter arterial embolization successfully controlled the hemorrhage, and the patient was discharged without complications. Systemic vascular screening revealed an asymptomatic right coronary artery dilation, necessitating medical management with statin therapy. This case highlights hepatic pseudoaneurysm as a rare but life-threatening vascular complication in STAT3-HIES. Given the potential for multi-organ vasculopathy, systemic vascular screening by contrast-enhanced CT or MRI is crucial for early detection and management. Further research is needed to elucidate the mechanisms underlying vasculopathy in STAT3-HIES and establish optimal screening strategies to improve patient outcomes.

PMID:40491905 | PMC:PMC12146391 | DOI:10.3389/fimmu.2025.1601776

Acta Derm Venereol. 2025 Jun 9;105:adv41318. doi: 10.2340/actadv.v105.41318.

ABSTRACT

Inborn errors of immunity are rare diseases and 50-80% present with dermatological manifestations. This study evaluated difficult-to-treat cutaneous human papillomavirus infections and their associations with immunological defects. Patients were recruited from the Dermatological Outpatient Clinic over 2 years. Patients reporting persistent common warts and/or a combination of molluscum contagiosum or more than 2 flat warts, with a clinical assessment of severe or persistent skin infection, met the clinical severity criteria for inclusion. Resistance to several therapies was also considered. A total of 632 patient records were analysed to clinically characterize the warts, laboratory data, treatments used and their responses, comorbidities, and family history. Among these, 459 cases were initially excluded from further evaluation. A questionnaire was provided by phone to 173 patients, among whom 47 patients were selected for an in-person consultation. Of these, 6 met the criteria for further evaluation. Immunological tests revealed neutropenia, low levels of immunoglobulin isotypes (IgA, IgM, and IgG), and reduced frequency of lymphocyte subsets. Family history, flat warts, and associated recurrent viral infections suggested the need for further immunological evaluation. Criteria are proposed for identifying patients with cutaneous warts that warrant additional evaluation for potential inborn errors of immunity.

PMID:40488587 | DOI:10.2340/actadv.v105.41318

J Transl Autoimmun. 2025 May 15;10:100292. doi: 10.1016/j.jtauto.2025.100292. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: Anti-γ interferon autoantibody (AIGA) syndrome is a widespread and grossly underestimated immunodeficiency disorder characterized by high mortality rates and a lack of standardized diagnostic methods. A highly accurate AIGA biomarker that meets the requirements of absolute quantification is urgently needed to enable the early diagnosis and treatment monitoring of the disease. In our study, we aimed to identify the primary components of AIGAs, determine their function, and develop a novel diagnostic method.

METHODS: Immune repertoire sequencing and a retrospective antibody subtype index analysis were performed for typical patients. Affinity chromatography was used to isolate and purify IgGs from AIGAs in the plasma of AIGA(+) patients. The clinical application value of chromatography for testing AIGAs was evaluated in a prospective clinical cohort.

RESULTS: A total of 114 eligible subjects were enrolled. Immune repertoire sequencing revealed that 74 % of the AIGA(+) patients had IgG clone types, with the somatic hypermutation (SHM) analysis being the most informative. We isolated AIGAs from the blood and interpreted their affinity and major components completely. Based on the results of this prospective cohort study, AIGAs, an absolute quantitative biomarker, were significantly better than the ELISA method (Delong test, P = 0.0018).

CONCLUSIONS: Patients with AIGA syndrome have abnormally elevated IgG levels, with IgG3 subtypes dominating. The disorder is characterized by the rapid acquisition of polyclonal AIGAs. The obtained AIGAs had a good neutralization capacity and potential as absolute quantitative biomarkers.

PMID:40485903 | PMC:PMC12143649 | DOI:10.1016/j.jtauto.2025.100292

Neuron. 2025 Jun 4:S0896-6273(25)00363-0. doi: 10.1016/j.neuron.2025.05.016. Online ahead of print.

ABSTRACT

Inborn errors of immunity (IEI), as congenital chronic disorders, are often associated with neurobehavioral symptoms, traditionally considered secondary to patient burden. Their origin, however, has yet to be addressed. Here, we found that IEI-associated genes are expressed in neural lineages during human brain development, and in the absence of immunological challenges, IEI mutations directly impair neurodevelopmental trajectories, leading to psychomotor defects. Warts hypogammaglobulinemia immunodeficiency myelokathexis (WHIM) mice-bearing a mutation causing Cxcr4 hyperactivation-show developmental foliation defects of the cerebellum correlating with sensorimotor and affective dysfunctions, which recapitulate the alterations described in patients. WHIM cerebella single-cell profiling revealed major transcriptional deregulation in granule cell progenitors, whose aberrant proliferation and migration induce foliation and circuit defects. AMD3100 intracerebroventricular injection rescues both morphological and behavioral defects, demonstrating their brain-specific and Cxcr4-dependent origin. Collectively, our findings highlight the relevance of neurodevelopmental implications underlying psychomotor IEI manifestations, broadening our understanding of these conditions beyond immune dysfunctions.

PMID:40482638 | DOI:10.1016/j.neuron.2025.05.016

BMC Cancer. 2025 Jun 5;25(1):1005. doi: 10.1186/s12885-025-14211-y.

ABSTRACT

BACKGROUND: Explosive tumor growth is characterized by rapid tumor growth in a short time period. Currently, there is no precise scientific definition for the condition, which is often accompanied with a poor clinical prognosis. Herein, we presented a study of a young patient with colon cancer who experienced explosive tumor growth. A clinical multidisciplinary team (MDT) collaborated with bioinformaticians to provide precise treatment and elucidate the biological mechanisms underpinning this growth.

METHODS: A 28-year-old male patient diagnosed with colon cancer experienced explosive tumor growth. Peripheral bloods (PB) during immunotherapy were collected for immune cytokine analyses and flow cytometry assays on immune cell subsets. To further examine the underlying mechanisms of this explosive-growth, we conducted whole exome sequencing (WES) and RNA-sequencing (RNA-seq) of samples taken at different time points.

RESULTS: The patient was diagnosed with Lynch syndrome. We implemented an immunotherapy and performed PB immune cytokine assays before, during, and after this therapy. Our observations suggested that immunotherapy may remodel interferon-gamma (IFN-γ) signaling and enhance T cell-mediated immune responses. By exploring explosive tumor growth mechanisms, we observed that tumors had significantly less insertion and deletion (INDEL) mutations and INDEL-derived neoantigens. Additionally, they had deficient antigen presentation functions as characterized by decreased IFN-γ signaling activity.

CONCLUSIONS: Neoantigen loss and decreased IFN-γ signaling activity contributed to explosive tumor growth in this patient. Recovered IFN-γ signaling may lead to effective immunotherapy outcomes.

PMID:40474074 | DOI:10.1186/s12885-025-14211-y

Microb Pathog. 2025 Jun 3:107776. doi: 10.1016/j.micpath.2025.107776. Online ahead of print.

ABSTRACT

Fungal infections, which affect approximately one billion people worldwide, pose significant health challenges due to their unique eukaryotic cell structures, requiring specialized treatments. Common fungal infections, such as dermatophyte-related conditions, vary from superficial to severe. Their prevalence is increasing due to factors like immunosuppression and acquired immunodeficiency syndrome (AIDS). While topical treatments are the primary approach, they often encounter limitations such as poor skin penetration. Additionally, conventional formulations require high doses and frequent administration. Recent advancements, including novel carriers, aim to overcome these challenges and reduce local side effects. This review highlights the innovations in transdermal drug delivery systems for antifungal agents, focusing on azoles, polyenes, echinocandins, allylamines, and other antifungal agents. Innovative delivery technologies, such as liposomes, microneedles, and microemulsions, are underscored to enhance skin permeation, improve drug stability, and ensure sustained release. The review emphasizes the improved efficacy and antifungal activity of these systems compared to traditional methods. It also addresses their safety and clinical potential, offering new strategies to improve treatment outcomes for fungal skin infections.

PMID:40473124 | DOI:10.1016/j.micpath.2025.107776

Cureus. 2025 May 5;17(5):e83507. doi: 10.7759/cureus.83507. eCollection 2025 May.

ABSTRACT

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare and complex primary immunodeficiency disorder. The classic clinical triad of APS-1 includes chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. Clinically, APS-1 presents with significant variability and is characterized by autoimmune dysfunction affecting both endocrine organs (including the parathyroids, adrenal glands, thyroid, gonads, and pituitary) as well as non-endocrine tissues (such as the skin, liver, kidneys, lungs, eyes, and intestines). Here we present a 23-year-old female with a history of abnormal body movement associated with posturing and transient loss of consciousness, along with a history of recurrent oral ulceration, itchy patches over intertriginous areas, and pigmentation of skin. Her examination was suggestive of low blood pressure, oral and cutaneous candidiasis, and hyperpigmentation of the skin. Routine investigations showed very low serum calcium, low parathyroid hormone (PTH) levels, and low early morning cortisol levels, and pathological calcification of the basal ganglia was noted on CT brain. As the patient met the diagnostic criteria of APS-1, she was treated accordingly and responded well.

PMID:40470404 | PMC:PMC12135895 | DOI:10.7759/cureus.83507

Front Cell Infect Microbiol. 2025 May 21;15:1570382. doi: 10.3389/fcimb.2025.1570382. eCollection 2025.

ABSTRACT

OBJECTIVES: This study aimed to analyze the clinical characteristics and genetic features of children with adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine. The goal was to improve understanding of this condition, provide insights into early diagnosis and intervention, and support stratified management.

METHODS: Clinical data of 35 children hospitalized at Kunming Children’s Hospital between January 2014 and June 2024 with complete records and diagnosed with BCG vaccine adverse reactions were collected. Cases were classified into two groups: disseminated BCG disease (BCG-D) and BCG-itis. Children with primary immunodeficiency (PID) were further divided into severe combined immunodeficiency (SCID) and non-SCID groups. Clinical characteristics, immunological profiles, genetic backgrounds, and outcomes were compared between the groups.

RESULTS: Among the 35 cases, 25 were male, and 10 were female, with a median age of onset of 2 months (1-4 months). Eight cases (22.9%) were diagnosed with BCG-D, while 27 cases (77.1%) were classified as BCG-itis. Sixteen cases (45.7%) were confirmed to have PID, including SCID (7 cases, 20.0%), chronic granulomatous disease (6 cases, 17.1%), Mendelian susceptibility to mycobacterial disease (2 cases, 5.7%), and fas associated via death domain (FADD) gene mutation (1 case, 2.6%). Compared to the BCG-itis group, the BCG-D group exhibited significantly higher rates of fever, hepatosplenomegaly, elevated white blood cell counts, neutrophil counts, and C-reactive protein (CRP) levels, along with lower red blood cell counts and hemoglobin levels (p<0.05). Similarly, the SCID group showed significantly lower age, lymphocyte counts, IgM levels, CD3, CD4, and CD8 cell ratios, but higher CD19 cell ratios and mortality rates compared to the non-SCID group (p<0.05). Twenty-seven (77.1%) cases were discharged after improvement, and eight children (22.9%) succumbed to the condition, including six with SCID gene mutations (representing 85.7% of the total SCID cases), one with an interleukin 12 receptor subunit beta 1(IL12RB1) mutation, and one who was not genetically tested but diagnosed with disseminated BCG disease.

CONCLUSIONS: In children presenting with adverse reactions to the BCG vaccine, the presence of fever, hepatosplenomegaly, elevated neutrophil levels, and CRP should prompt evaluation for disseminated BCG disease and assessment of immunological status. Early identification of underlying PID, particularly SCID, is crucial, given the high mortality and poor prognosis associated with the condition, necessitating timely interventions.

PMID:40470261 | PMC:PMC12133749 | DOI:10.3389/fcimb.2025.1570382