Research

Int J Infect Dis. 2026 Jan 25:108438. doi: 10.1016/j.ijid.2026.108438. Online ahead of print.

ABSTRACT

BACKGROUND: Anti-interferon-γ autoantibody syndrome (AIGAs) is a primary immunodeficiency disorder characterized by neutralizing autoantibodies blocking IFN-γ signaling, predisposing patients to severe opportunistic infections. No definitive treatment protocol exists, and conventional therapies carry infection risks. Hemoadsorption (HA) is effective for autoimmune diseases but has not been specifically investigated for AIGAs.

CASE PRESENTATION: A 65-year-old Chinese female was admitted with 10-month painless disseminated lymphadenopathy. 18F-FDG PET/CT showed multiple hypermetabolic lymph nodes, and ultrasound-guided biopsy revealed necrotizing granulomatous inflammation. Metagenomic next-generation sequencing (mNGS) identified Mycobacterium abscessus, and ELISA confirmed high AIGA levels (88.05% at 1:3200 dilution). She received anti-nontuberculous mycobacteria (NTM) therapy (clarithromycin, minocycline, contezolid) combined with one HA session using a cytokine adsorption column. Post-treatment, AIGA levels normalized to 0% at 24 weeks and remained stable. 72-week follow-up showed resolved lymphadenopathy and reduced lymph node size/metabolic activity on PET/CT.

CONCLUSION: This is the first report of single-session HA for AIGAs complicated by disseminated Mycobacterium abscessus infection. HA effectively reduced AIGA levels, controlled infection, and avoided global immunosuppression, providing a promising adjunctive therapy for AIGAs patients with severe disseminated infections.

PMID:41592665 | DOI:10.1016/j.ijid.2026.108438

Allergy Asthma Immunol Res. 2026 Jan;18(1):132-144. doi: 10.4168/aair.2026.18.1.132.

ABSTRACT

PURPOSE: The impact of coronavirus disease 2019 (COVID-19) on patients with primary immunodeficiency (PID) remains insufficiently characterized. This study aimed to describe the clinical manifestations, disease course, and outcomes of COVID-19 in patients with PID.

METHODS: Adult patients with PID who had COVID-19 infection between March 2020 and August 2022 were screened. Demographic and clinical data were retrospectively collected from institutional databases, and additional information was obtained through a patient questionnaire.

RESULTS: A total of 36 patients (19 males, 17 females; median age: 36.5 years) with various PID subtypes were included: 24 with common variable immunodeficiency (CVID), 3 with cytotoxic T-lymphocyte-associated protein-4 haploinsufficiency, 3 with X-linked agammaglobulinemia (XLA), 2 with hypogammaglobulinemia, 1 with lipopolysaccharide-responsive and beige-like anchor protein deficiency, 1 with DiGeorge syndrome, 1 with mitochondrial neurogastrointestinal encephalomyopathy syndrome, and 1 with CVID-like capillary malformation-arteriovenous malformation syndrome 2. Overall, 63.9% (n = 23) were managed as outpatients, while 36.1% (n = 13) required hospitalization. Admission to the intensive care unit was required in 19.4% (n = 7) of the cases. The overall case fatality rate was 8.3% (n = 3), which is higher than the rate observed in the general population. Although the majority experienced a mild clinical course, patients with XLA exhibited prolonged symptoms and persistent seropositivity. Risk factors associated with hospitalization included lymphopenia, elevated C-reactive protein and ferritin levels, dyspnea, COVID-19 Reporting and Data System score ≥ 4 on imaging, need for supplemental oxygen, prolonged symptoms, and extended polymerase chain reaction positivity.

CONCLUSIONS: A subset of adult patients with PID may be at increased risk for severe COVID-19.

PMID:41592542 | DOI:10.4168/aair.2026.18.1.132

Ophthalmol Sci. 2025 Dec 3;6(2):101027. doi: 10.1016/j.xops.2025.101027. eCollection 2026 Feb.

ABSTRACT

PURPOSE: To evaluate conventional imaging modalities for detecting fibrosis in neovascular age-related macular degeneration (nAMD) and to develop a standardized diagnostic workflow.

DESIGN: Systematic discussion and grading exercise assessing multiple imaging modalities.

PARTICIPANTS: Retina specialists from the International Fibrosis Consensus workgroup and members of the International Retinal Imaging Society.

METHODS: An international panel assessed the advantages and limitations of 5 imaging modalities-color fundus photography (CFP), fluorescein angiography (FA), spectral domain OCT (SD-OCT), near-infrared reflectance, and fundus autofluorescence-for detecting fibrosis in nAMD. A structured debate was followed by 2 online, masked image grading surveys. Sensitivity, specificity, and predictive accuracy of each modality, alone and in combination, were determined. Intergrader agreement was calculated. Imaging features were also correlated with histology in a nonhuman primate laser model. Based on consensus discussions at 2 in-person meetings and survey results, a 2-step diagnostic approach using SD-OCT as the primary modality was proposed.

MAIN OUTCOME MEASURES: Recommendation for a standardized approach for diagnosing fibrosis in eyes with nAMD.

RESULTS: Among the 5 modalities, SD-OCT was considered essential by all workgroup members. Hyperreflective material on OCT was unanimously identified as a key indicator of fibrosis. However, its limited specificity was acknowledged. In 2 masked grading exercises, SD-OCT showed the highest sensitivity (0.88 and 0.84) but only moderate specificity (0.56 and 0.57). The area under the curve (AUC) for SD-OCT was 0.72 and 0.70. A 2-step strategy combining SD-OCT with CFP or FA improved diagnostic accuracy. Hyperreflective material was defined as material with reflectivity equal to or greater than normal retinal pigment epithelium (RPE), well-defined margins, RPE disruption, and a laminated appearance. Corresponding CFP findings included well-defined yellow/white/gray subretinal lesions, and FA findings included early blocked fluorescence and late staining. This 2-step approach increased AUC to 0.85, with sensitivity of 0.83 and specificity of 0.87.

CONCLUSIONS: The study establishes a 2-step approach using OCT as the primary modality in clinical studies for the detection of fibrosis.

FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PMID:41584096 | PMC:PMC12830330 | DOI:10.1016/j.xops.2025.101027

Front Immunol. 2026 Jan 8;16:1735023. doi: 10.3389/fimmu.2025.1735023. eCollection 2025.

ABSTRACT

INTRODUCTION: This study aims to present in a large real-world cohort a diagnostic algorithm developed to facilitate the early recognition of Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS), a rare disease with targeted treatment options, and to provide clinicians with a practical roadmap for navigating diagnostic challenges.

METHODS: The study was conducted as a retroactive cross-sectional observational study. We reviewed the medical records of 6,458 pediatric and adult patients who were referred to our clinic between 2018 and 2025. A medical algorithm was generated based on major clinical and laboratory features of APDS. Next-generation sequencing analyses were performed on patients who were appropriate for further evaluation. Variant analysis using in silico predictors and S6 phosphorylation analysis in patients carrying previously undescribed variants were conducted accordingly.

RESULTS: In this cohort of 6,458 patients, the diagnostic algorithm identified 1,138 who met at least one major clinical or laboratory criterion. After excluding 7 with a prior APDS diagnosis and 573 with other inborn errors of immunity, genetic analysis was performed in 20 consenting patients under clinical follow-up (11 [55%] female, 9 [45%] male; median age 15 years; IQR 7.5-24). APDS type 2 was confirmed in 1 patient; five others harbored novel variants of uncertain significance.

CONCLUSION: Delayed diagnosis and treatment of APDS may result in life-threatening complications and irreversible end-organ damage. Given its heterogeneous, overlapping phenotype, timely referral for genetic testing is essential.

PMID:41583441 | PMC:PMC12823944 | DOI:10.3389/fimmu.2025.1735023

Hum Pathol. 2026 Jan 22:106051. doi: 10.1016/j.humpath.2026.106051. Online ahead of print.

ABSTRACT

BACKGROUND: Primary central nervous system immunodeficiency/dysregulation-associated lymphoproliferative disorders (PCNS-IDD-LPDs) are a rare and heterogeneous group of lymphoid lesions that arise within the CNS of immune compromised patients. Among PCNS-IDD-LPDs, monomorphic IDD-LPDs are relatively well studied; however, data regarding PCNS polymorphic IDD-LPDs is very limited. It remains unclear whether polymorphic PCNS IDD-LPDs follow a similarly indolent clinical course as observed in their systemic polymorphic counterparts, or whether the unique immune microenvironment of the CNS imparts a more aggressive disease biology.

METHODS: In this study, we compared the clinical, pathologic, and survival profile of PCNS polymorphic IDD-LPDs (N=15) with extra-CNS polymorphic IDD-LPDs (N=21) as well as PCNS monomorphic IDD-LPDs (N=12).

RESULTS: Compared to extra-CNS polymorphic IDD-LPDs, patients with PCNS polymorphic IDD-LPDs showed a significantly stronger association with kidney transplants, longer latency, worse performance status, more frequent monoclonal populations and necrosis, and a greater need for aggressive chemoimmunotherapy in addition to reduction in immunosuppression and/or rituximab. The overall survival (OS) of PCNS polymorphic IDD-LPDs was significantly inferior to that of extra CNS polymorphic IDD-LPDs (median survival: 7.1 years vs. not reached; log-rank p=0.023) and not significantly different from PCNS monomorphic IDD-LPDs (median survival: 7.1 vs. 3.6 years; log-rank p=0.852).

CONCLUSION: We conclude that PCNS polymorphic IDD-LPDs have a uniquely aggressive clinicopathologic and prognostic profile compared to their systemic counterparts and are comparable to their monomorphic PCNS counterparts. CNS localization supersedes the histological subtype as the primary determinant of disease biology in IDD-LPDs, likely ascribed to the immune sanctuary status of the CNS.

PMID:41580209 | DOI:10.1016/j.humpath.2026.106051

Scand J Immunol. 2026 Feb;103(2):e70092. doi: 10.1111/sji.70092.

ABSTRACT

Jeffrey Modell warning signs have been used to guide screening for inborn errors of immunity (IEIs) for over three decades now, but may lack sensitivity for noninfectious presentations. Our study explored JMF signs along with additional signs and some laboratory parameters and assessed their effectiveness for guiding molecular screening for IEIs. We retrospectively analysed 100 patients suspected of IEI referred to ICMR-National Institute of Immunohaematology from immunology clinics who underwent whole-exome sequencing (WES), with pathogenic (n = 50) and no variants (n = 50). We evaluated clinical presentations other than JMF-autoimmunity, autoinflammation, vaccine complications, fever with bi-cytopenia, consanguinity and laboratory parameters-absolute lymphocyte count, low naïve T cell (%) and hypogammaglobulinaemia at initial presentation. Thirty-two models with different combinations of additional signs along with JMF score were evaluated based on the AIC score to determine the best model. The model was validated on WES results of 219 patients. The JMF scores of the pathogenic/likely pathogenic group (3.54 ± 1.92) were significantly higher than those of the no variants group (1.34 ± 1.28) (p < 0.05). The best model, inclusive of consanguinity, presence of autoimmunity, vaccine complications, hypogammaglobulinaemia and low naïve T cell (%) with JMF, had a sensitivity and specificity of 82% and 67%, respectively, compared to sensitivity and specificity of 84% and 61% for JMF alone. Our study shows that the presence of any two among parental consanguinity, presence of autoimmunity, vaccine complications and low naïve T cell (%) improves the specificity of JMF criteria in guiding molecular screening for IEIs.

PMID:41580301 | DOI:10.1111/sji.70092

Medicine (Baltimore). 2026 Jan 23;105(4):e47367. doi: 10.1097/MD.0000000000047367.

ABSTRACT

Pediatric lymphoproliferative disorders (PLPDs) encompass a spectrum of conditions marked by the abnormal proliferation of lymphocytes, often linked to genetic mutations, immune dysregulation, and infectious agents like Epstein-Barr virus. These disorders present with varied clinical phenotypes, ranging from benign lymphadenopathy to severe, life-threatening malignancies. Recent advancements in molecular diagnostics and imaging have significantly enhanced the early identification and classification of PLPDs, paving the way for timely and effective interventions. Understanding the pathophysiological mechanisms underlying PLPDs has also been instrumental in guiding the development of novel therapeutic strategies. The management of PLPDs has evolved with the advent of targeted therapies, including monoclonal antibodies and small molecule inhibitors, which have demonstrated promising efficacy in mitigating disease progression. For severe or refractory cases, hematopoietic stem cell transplantation remains a curative option, especially for disorders associated with primary immunodeficiencies. Despite these advancements, challenges persist in ensuring equitable access to advanced diagnostics and therapies, particularly in resource-limited settings. Furthermore, optimizing treatment regimens to minimize long-term complications and improve quality of life remains a critical area of focus.

PMID:41578561 | DOI:10.1097/MD.0000000000047367

Medicine (Baltimore). 2026 Jan 23;105(4):e44410. doi: 10.1097/MD.0000000000044410.

ABSTRACT

RATIONALE: Hereditary angioedema (HAE) is a rare genetic disorder caused by C1 esterase inhibitor (C1-INH) deficiency or dysfunction. Presentation with isolated abdominal pain is uncommon, often leading to diagnostic delays and inadequate pain management. Effective pain control is essential to improve patient comfort and prevent complications.

PATIENT CONCERNS: A 21-year-old male with type II HAE presented exclusively with recurrent severe abdominal pain and experienced a transient loss of consciousness attributed to a pain-induced vagal reflex.

DIAGNOSES: Diagnosis of type II HAE was confirmed based on clinical presentation, laboratory findings of C1-INH dysfunction, and exclusion of other causes of abdominal pain.

INTERVENTIONS: The patient received multidisciplinary care including symptom-based nursing, targeted pharmacological therapy with lanadelumab, psychological support, and nutritional management.

OUTCOMES: Following lanadelumab administration, the patient’s abdominal pain improved significantly within 2 hours and completely resolved within 8 hours. Symptom relief was sustained at 3-month follow-up with no recurrence.

LESSONS: This case underscores the importance of early recognition of HAE presenting solely with abdominal pain and demonstrates that multidisciplinary, targeted pain management can lead to rapid and sustained symptom relief. Awareness of such atypical presentations is critical for optimizing outcomes in HAE patients.

PMID:41578566 | DOI:10.1097/MD.0000000000044410

Turk J Gastroenterol. 2025 Aug 25;37(1):55-61. doi: 10.5152/tjg.2025.25100.

ABSTRACT

BACKGROUND/AIMS: The aim was to determine the findings of the gastrointestinal system, which is the second most frequently affected system in the primary immunodeficiency (PID) patient population, and the frequency of these findings.

MATERIALS AND METHODS: Fifty patients with PID were included in this study, and the characteristics of the patients, upper gastrointesti nal endoscopy, colonoscopy, and biopsy (endoscopic and colonoscopic) results were evaluated.

RESULTS: The median age of patients included in the study was 31 years (range 18-72 years) and 64% were male. Seventy-two percentnof the patients had common variable immunodeficiency (CVID) and 68% were diagnosed in adulthood. Chronic diarrhea was present in 48% of the patients, and body mass index was lower in this group. Switched memory B cells were lower in chronic diarrhea (P = .003). Twenty-nine patients underwent upper gastrointestinal endoscopy, and the most common macroscopic findings were gastropathy (79.3%), duodenopathy (37.9%), and esophagitis (27.6%). Of the 23 patients who underwent colonoscopy, 14 had at least 1 macro scopic finding other than internal hemorrhoids and only 1 patient had no macroscopic findings. One patient had mucosa-associated lymphoid tissue lymphoma (MALToma) on gastric biopsy, while 1 patient had poorly differentiated adenocarcinoma on antrum biopsy.

CONCLUSION: In conclusion, chronic diarrhea is more common in PID than in the general population, and switched memory B cells arenlower in PID patients with chronic diarrhea. Most importantly, a collaboration between immunologists, gastroenterologists, and patholo gists is required when evaluating the gastrointestinal tract in PID. Cite this article as: Erkoç M, Erhan Ç, Çevirme L, et al. Gastrointestinal tract findings in patients with primary immunodeficiency: A single-center 6-year experience. Turk J Gastroenterol. 2026;37(1):55-61.

PMID:41578787 | DOI:10.5152/tjg.2025.25100

Front Immunol. 2026 Jan 7;16:1736589. doi: 10.3389/fimmu.2025.1736589. eCollection 2025.

ABSTRACT

INTRODUCTION: Stressful physical or psychological events can trigger acute swelling attacks in patients with Hereditary Angioedema due to C1 Inhibitor deficiency (HAE-C1INH), although the stress-disease relationship remains unclear. The Socially Evaluated Cold Pressor Test (SECPT) reliably induces acute stress under controlled conditions. This study aimed to compare perceived stress, inflammatory markers, and cardiovascular responses to SECPT between HAE-C1INH patients and healthy controls (HC).

METHODS: Twenty HAE-C1INH patients (9 males, 44 ± 14 years) and age and sex matched HC underwent a 3-minute SECPT. Participants completed questionnaires assessing anxiety and depression (HADS), pain catastrophizing (PCS), and subjective stress (0-100 scale) before and after SECPT. Heart rate (HR) and arterial pressure (AP) were recorded. Blood samples for inflammatory cytokines (IL-6, IL-1ß, TNF-α) were collected at baseline, and 10 and 40 minutes after SECPT.

RESULTS: Compared to HC, patients showed higher baseline HADS-A (7.3 ± 4.5 vs 4.7 ± 2.7), overall PCS (19.7 ± 12.6 vs 12.9 ± 8.7), and perceived stress during SECPT (60.6 ± 34.3 vs 34.6 ± 23.8). IL-6 levels were higher at baseline and 10 minutes post-test (2.63 ± 1.21 vs 1.84 ± 0.87; 2.78 ± 1.20 vs 1.91 ± 0.79 pg/ml), as were TNF-α levels across all phases (4.19 ± 1.38 vs 3.26 ± 1.55; 4.09 ± 1.39 vs 3.40 ± 1.48; 4.09 ± 1.28 vs 3.20 ± 1.57) while IL-1 ß remained unchanged. HR and AP variations were similar between groups.

DISCUSSION: HAE-C1INH patients exhibited heightened perceived stress response to SECPT, and elevated baseline inflammation, despite comparable cardiovascular reactivity. These findings highlight a complex psychophysiological-inflammatory interplay in acute stress responses, suggesting the need to integrate psychological and biological frameworks in understanding HAE-C1INH triggers.

CLINICAL TRIALS CODE: NCT06414252.

PMID:41573571 | PMC:PMC12819172 | DOI:10.3389/fimmu.2025.1736589