Research

J Allergy Clin Immunol Pract. 2026 Feb;14(2):375-383. doi: 10.1016/j.jaip.2025.11.039.

ABSTRACT

Hereditary angioedema (HAE) with C1-inhibitor deficiency is a rare condition presenting with episodes of swelling without urticaria. Historically, acute and prophylactic HAE treatment options were limited and associated with considerable side effects, high burden of treatment, and unreliable symptom relief. Over the past decade, newer targeted therapies have been investigated and approved for both acute therapy and long-term prophylaxis. These therapies have dramatically reduced morbidity and mortality of HAE and consequently improved the quality of life of patients. This review article will outline the current and potential future treatments for HAE.

PMID:41654335 | DOI:10.1016/j.jaip.2025.11.039

Ann Chir Plast Esthet. 2026 Feb 6:S0294-1260(25)00174-8. doi: 10.1016/j.anplas.2025.11.008. Online ahead of print.

ABSTRACT

INTRODUCTION AND IMPORTANCE: Pyoderma gangrenosum (PG) is a rare condition caused by dermal inflammation with neutrophilic infiltration, often associated with an underlying systemic disease. The breast is an uncommon site for this condition. It is an exclusion diagnosis, challenging to establish, which may initially lead to an alternative one and the initiation of inappropriate treatment.

PRESENTATION OF CASE: A 41-year-old woman with a medical history of morbid obesity, breast reduction 14 years ago, common variable immunodeficiency (CVID), and autoimmune thrombocytopenia presented with a spontaneous inflammatory ulcer of the left breast. The clinical course rapidly deteriorated, progressing to septic shock despite antibiotics. This presentation led to the consideration of necrotizing soft tissue infection (NSTI) as the primary diagnosis. The patient underwent multiple surgical debridements combined with broad- spectrum antibiotic therapy, which resulted in only a slow improvement in her condition. Histopathological examination of the surgical specimens revealed a cutaneous ulcer with dermal inflammation predominantly composed of neutrophils. Her condition eventually stabilized, allowing for reconstruction of the left breast with a split-thickness skin graft. In the immediate postoperative period, the patient developed a fever of unknown origin and inflammatory lesions with a violaceous border at the graft donor site. PG was suspected. One month later, the patient presented with a spontaneously occurring violaceous inflammatory lesion on the controlateral breast.

CLINICAL DISCUSSION: This case of spontaneous PG, is a condition only very rarely described in the literature. A combination of concordant findings support this diagnosis.

CONCLUSION: PG is a rare condition with a challenging diagnosis, as it is one of exclusion. The breast is an uncommon site of involvement, typically described in postoperative cases and very rarely presenting spontaneously. When a patient presents with breast dermo-hypodermitis that shows limited improvement despite appropriate treatment, PG should be considered as a differential diagnosis.

PMID:41654471 | DOI:10.1016/j.anplas.2025.11.008

Front Immunol. 2026 Jan 21;16:1742293. doi: 10.3389/fimmu.2025.1742293. eCollection 2025.

ABSTRACT

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare, autosomal recessive primary immunodeficiency, with fewer than 120 cases reported worldwide. ICF type 1 (ICF1) is the most prevalent subtype. Despite its rarity, ICF1 presents a distinct set of clinical features that necessitate increased awareness, particularly in populations with high rates of consanguinity. This case presents a two-year-old Palestinian boy born to consanguineous parents who presented with recurrent respiratory tract infections, facial dysmorphisms, and hypogammaglobulinemia. A comprehensive immunologic evaluation confirmed markedly reduced immunoglobulin levels consistent with an antibody deficiency. Genetic testing identified a homozygous missense mutation in DNMT3B (Arg826Cys), establishing the diagnosis. The patient was started on intravenous immunoglobulin (IVIG) replacement therapy, which was well tolerated and led to a noticeable reduction in infection frequency and an overall clinical well-being improvement. While treatment remains supportive, early recognition and immunologic management can significantly reduce morbidity. This case highlights the importance of early diagnosis and immunologic support in ICF1 syndrome, reinforces genotype-phenotype correlations, and provides valuable insights from an underrepresented region to improve global awareness, diagnosis, and care, being only the second genetically confirmed case from Palestine.

PMID:41646978 | PMC:PMC12867814 | DOI:10.3389/fimmu.2025.1742293

Fundam Res. 2023 Nov 2;6(1):498-508. doi: 10.1016/j.fmre.2023.09.004. eCollection 2026 Jan.

ABSTRACT

Cancer can educate platelets by altering transcriptome profiles. However, the exact education mechanism remains unclear, and the variability of tumor-educated platelet (TEP) transcriptome has not been investigated. In this study, we aimed to build a stratification system for TEP based on machine learning (ML) data-driven patterns and platelet transcriptome profiles. This study included platelet samples from 1,628 cancer participants from European and United States populations, including 18 different and most prevalent types of cancer. Gaussian mixture model (GMM) was used to identify robust clusters and similar education pattern. While extreme gradient boosting (XGBoost) was used to precisely predict the clusters. Three clusters were eventually identified. The cluster results showed robustness and generality, reflected by comparable patterns of important gene expression, cancer type prevalence, and biological annotation across derivation, evaluation and validation cohorts. Cluster 1 (n = 346), mainly participated in drug metabolism cytochrome P450, metabolism of xenobiotics by cytochrome P450, and glutathione metabolism. Cluster 2 (n = 538) mainly participated in ribosome, spliceosome, and primary immunodeficiency. Cluster 3 (n = 744) mainly participated in gap junction and focal adhesion. Based on this novel cluster system, further observational study can investigate the association between these clusters and cancer progression, prognosis, cancer associated thrombosis, treatment resistance (both chemotherapy and immunotherapy), and immune cell infiltration. Overall, in this study, we built the first pan-cancer TEP stratification system based on data-driven patterns of ML and platelet transcriptional profiles. These clusters could help us better understand the variability of the pan-cancer education mechanism.

PMID:41647571 | PMC:PMC12869750 | DOI:10.1016/j.fmre.2023.09.004

Probl Endokrinol (Mosk). 2025 Dec 2;71(5):47-57. doi: 10.14341/probl13555.

ABSTRACT

22nd chromosome deletion syndrome (22q11.2 DS, del22q11.2) (with severe immunological disorders – Di Georg syndrome (SDH) or Di Giorgi syndrome (SDD)) It is one of the most common microdeletion syndromes.The disease is based on a violation of the formation of organs originating from the third gill arch.There is a full form of del22q11.2 syndrome with severe primary immunodeficiency (PID), congenital heart defects (CHD), hypoparathyroidism, facial skeletal abnormalities and high mortality during the first year of life, and partial forms without PID and calcium-phosphorus metabolism disorders.The high variability of clinical manifestations explains the fact that there are many different names of the disease in the literature: Di Giorgi syndrome (SDD), Di Georg syndrome (SDH), CATCH 22, velocardiofacial syndrome, Kyler syndrome, Sprintzen syndrome, facial and conotruncal abnormalities, etc.The term «Di Giorgi syndrome» is applicable to cases of deletion of 22q11.2 chromosome occurring with immune disorders. Despite the availability of genetic testing, many cases of 22q11.2 deletion syndrome remain undiagnosed due to its multsystem nature and varying severity of clinical manifestations, which is associated with a high risk of life-threatening complications.We present data from a 9-year-old patient with a partial form of deletion syndrome 22q11.2, when the reason for contacting an endocrinologist was the early appearance of secondary sexual characteristics against the background of decompensated primary hypothyroidism (Van Wyk-Grombach syndrome) in the absence of violations of phosphorus-calcium metabolism and PID.This clinical case demonstrates not only the variability of the clinical symptoms of the disease, but also the need for coordinated interaction of specialists from various specialties to diagnose polymorphic chromosomal pathology.

PMID:41640147 | DOI:10.14341/probl13555

Postepy Dermatol Alergol. 2025 Dec 18;42(6):572-578. doi: 10.5114/ada.2025.158074. eCollection 2025.

ABSTRACT

INTRODUCTION: Some diseases, including primary immunodeficiencies (PID), require treatment with intravenous immunoglobulin (IVIG). IVIG is an effective treatment and is generally well tolerated. IVIG can cause side effects ranging from mild reactions to, in rare cases, serious complications such as anaphylaxis.

AIM: We aimed to assess the frequency, types, and severity of adverse effects in adults receiving IVIG for PID, and to examine associated risk factors and the impact of premedication.

MATERIAL AND METHODS: This retrospective cohort study analysed 90 patients and 6246 IVIG infusions administered at the Gülhane Training and Research Hospital between 2016 and 2024. Demographic data, comorbidities, IVIG-related side effects, and treatment processes of the patients were examined.

RESULTS: A total of 6246 IVIG infusions were evaluated, 363 (5.8%) of which had side effects. Side effects mostly occurred within the first 6 h of infusion (early reaction) (75.2%). The most frequently preferred intervention was to reduce the infusion rate (37.5%), followed by stopping the treatment (27.5%) and using antihistamines (22.5%). Serious cases such as anaphylaxis were rare (0.12%) and could be controlled with appropriate interventions. The rate of side effects was significantly lower in patients who received premedication.

CONCLUSIONS: Our study highlights that side effects associated with IVIG treatment are generally mild and manageable, but careful monitoring and individualized premedication protocols are important for preventing side effects and patient safety.

PMID:41640478 | PMC:PMC12866531 | DOI:10.5114/ada.2025.158074

J Clin Immunol. 2026 Feb 3. doi: 10.1007/s10875-025-01978-9. Online ahead of print.

ABSTRACT

PURPOSE: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is successful in pediatric patients with inborn errors of immunity (IEI), but its use in adults is complicated by pre-existing organ damage and increased risk of treatment-related mortality. Ex vivo graft engineering using αβTCR/CD19 depletion has shown promising safety profiles in pediatric IEI, yet evidence in adults is limited. We assessed the feasibility and outcomes of αβTCR/CD19-depleted allo-HSCT in adults with IEI, focusing on engraftment, immune reconstitution, and clinical outcomes.

METHODS: We included 9 adults with IEI and 1 with VEXAS (age 21-51). IEIs included CTLA4HI, APDS, DOCK8, ALPS, DADA2, CVID2, and HA20, with Immune Deficiency and Dysregulation Activity (IDDA) scores of 17-92. αβTCR/CD19-depleted allografts from related, unrelated or haplo-identical donors were used after antithymocyte globulin (ATG) and myeloablative conditioning (thiotepa, melphalan, and fludarabine). Post-transplant immunoprophylaxis included mycophenolate mofetil; 4/10 patients received additional transplant-associated immunosuppression.

RESULTS: All patients achieved primary engraftment. One patient with secondary rejection successfully underwent a second allo-HSCT. 5 patients developed grade 2-4 acute GvHD; no chronic GvHD was observed. One patient with GvHD died from COVID-19. All remaining 9 patients were successfully tapered off immunosuppression and showed improved IDDA scores. At 6 months NK, γδT, B and CD8 + T cells normalized; CD4 + numbers reached 149 cells/µl at 1 year. Most patients were successfully vaccinated and could stop immunoglobulin substitution.

CONCLUSION: In conclusion, ex vivo graft engineering using αβTCR/CD19 depletion was feasible in adults with IEI. Clinical outcomes are encouraging, but need to be confirmed in larger studies.

PMID:41634270 | DOI:10.1007/s10875-025-01978-9

J Leukoc Biol. 2026 Feb 3:qiag020. doi: 10.1093/jleuko/qiag020. Online ahead of print.

ABSTRACT

Despite advances in engineered adaptive immune cell therapies, current options for innate immune cell therapies are sparse. In this work, we demonstrate the utility of a neutrophil progenitor-based cell therapy. Murine conditionally-immortalized neutrophil progenitors (NPs) overcome some of the hurdles of alternative cell therapies, such as granulocyte transfusion, by engrafting in the unconditioned host and undergoing substantial expansion in vivo. Here we demonstrate the therapeutic value of NPs using a murine model of the primary immunodeficiency chronic granulomatous disease (CGD). Those with CGD are highly susceptible to infection with Staphylococcus aureus because of genetic mutations that impair neutrophil antimicrobial function. We find that the prophylactic treatment of CGD mice with transfused NPs rescue them from an otherwise lethal S. aureus pulmonary infection. In investigating the mechanisms behind the improved clearance of S. aureus and survival of CGD mice, our data suggests that the antimicrobial function of host CGD neutrophils is rescued by the presence of donor-derived wild-type neutrophils. We also observe that survival is improved to >50% in the CGD model when mice receive NPs post-infection. This work highlights the application of NPs to improving outcomes to acute bacterial infection in CGD, demonstrating the translational potential of conditionally-immortalized myeloid progenitors as a cellular therapy.

PMID:41632796 | DOI:10.1093/jleuko/qiag020

Allergy Asthma Clin Immunol. 2026 Feb 2. doi: 10.1186/s13223-026-01016-2. Online ahead of print.

ABSTRACT

BACKGROUND: WHIM syndrome is a rare autosomal dominant primary immunodeficiency characterized by the classical tetrad of warts, hypogammaglobulinemia, infections, and myelokathexis. The majority of cases are associated with gain-of-function mutations in the CXCR4 gene. Recent studies have expanded the clinical spectrum of the disease, revealing that only a subset of patients present with all four hallmark features. This underscores the syndrome’s variable expression and the need for greater clinical awareness of its atypical forms.

CASE PRESENTATION: We report a case of a 6-year-old Saudi girl who presented with persistent neutropenia, recurrent upper respiratory infections, and an episode of thrombocytopenia following a dental procedure. She did not exhibit warts, hypogammaglobulinemia, or myelokathexis. Immunological workup revealed marked lymphopenia affecting T, B, and NK cells, while immunoglobulin levels remained within normal limits. Bone marrow findings were unremarkable. Whole-exome sequencing identified a heterozygous de novo CXCR4 frameshift mutation (c.1172_1173del), confirming the diagnosis of WHIM syndrome. The patient was clinically stable and managed conservatively with precautions.

CONCLUSION: This case contributes to the evolving understanding of the clinical variability in WHIM syndrome and highlights the importance of genetic testing in patients with unexplained neutropenia and recurrent infections, even in the absence of the complete clinical tetrad.

PMID:41629964 | DOI:10.1186/s13223-026-01016-2

Genome Biol. 2026 Feb 2. doi: 10.1186/s13059-026-03974-7. Online ahead of print.

ABSTRACT

BACKGROUND: Beta-thalassemia is among the most common monogenic disorders, posing a major global health challenge. Editing of genetic modifiers, such as BCL11A erythroid enhancer and HBG promoters, enhances fetal hemoglobin expression and confers major therapeutic potential. Double-strand-break (DSB)-independent genome editing tools, such as base editors (BE), are potentially safer and better suited for multiplexed application than DSB-dependent CRISPR/Cas technology. However, harmful on- and off-target events remain a concern and must be excluded before clinical application, including chromosomal rearrangements invisible to standard detection technologies.

RESULTS: Using primary patient-derived CD34⁺ cells from three donors, we investigate simplex and duplex BE-based disruption of the BCL11A erythroid enhancer and the BCL11A binding site (-115 bp) on the HBG promoter for DNA-level and functional studies at the RNA, protein, and morphological level. Analyses include direct comparison to DSB-based editing, the current clinically applied standard, and CAST-seq to assess recombination events, allowing wider inferences on relative safety. RNA-seq analyses for clones of primary CD34⁺ cells across all treatments confirm peak HBG induction for duplex BE and comparable effects on apoptotic and immune response signatures. Overall, duplex BE produces robust γ-globin and fetal hemoglobin induction, improves functional correction over simplex editing and results in low incidence of genomic alterations in both target loci.

CONCLUSIONS: Duplex BE targeting both BCL11A erythroid enhancer and HBG promoter enables functional correction and genome integrity. Our study highlights the efficacy, safety, and therapeutic potential of the present duplex BE approach.

PMID:41629994 | DOI:10.1186/s13059-026-03974-7