Research

Eur J Immunol. 2026 Feb;56(2):e70148. doi: 10.1002/eji.70148.

ABSTRACT

Complement factor B (FB) deficiency is an extremely rare alternative pathway (AP) defect predisposing to invasive infections, with only three families reported to date. We investigated a 14-year-old girl who developed Neisseria meningitidis serogroup Y meningitis complicated by bacteremia and cerebral venous sinus thrombosis. Complement function was assessed by TCA and AP50 hemolytic assay, FB quantification, and functional reconstitution with purified proteins. Genetic analysis of CFB was performed by next-generation sequencing. TCA, C3, and C4 were normal, whereas AP50 was undetectable. Plasma FB concentration was reduced. Reconstitution with purified FB, but not FD, restored AP activity, confirming FB deficiency. Patient plasma failed to support C3b-dependent hemolysis. Sequencing revealed compound heterozygosity for two missense variants in CFB: p.Gly396Arg in the vWFA domain (previously described) and p.Gln713Arg, a novel substitution in the serine protease domain near the catalytic Ser699. Both were classified as likely pathogenic according to ACMG criteria. This report represents the third genetically confirmed case of complete FB deficiency and the first involving a serine protease domain variant. It underscores the diagnostic value of combined quantitative and functional complement assays and highlights infectious risks relevant to patients treated with emerging FB inhibitors.

PMID:41663882 | DOI:10.1002/eji.70148

Clin Case Rep. 2026 Feb 5;14(2):e71988. doi: 10.1002/ccr3.71988. eCollection 2026 Feb.

ABSTRACT

Immunoglobulin replacement therapy (IRT) for primary immunodeficiency reduces infection risk and subsequent complications and can be lifesaving. However, IRT can cause severe systemic adverse events (AEs) that may limit adequate dosing. These AEs may be caused, in part, by activation and/or consumption of complement proteins, thereby lowering C1 esterase inhibitor (C1-INH) levels. Data suggest that C1-INH administration prior to intravenous immunoglobulin (IVIG) may reduce IVIG-related AEs. This case describes an adult with common variable immunodeficiency unable to tolerate IRT therapy (subcutaneous immunoglobulin [SCIG] 20% solution once weekly). She experienced AEs of severe neuropathy, described as burning and pins-and-needles sensation in the extremities and muscle twitching for several days post-treatment. Dose decreases of SCIG to 0.5 g did not improve the AE profile. Inability to tolerate IRT caused suboptimal dosing and inadequate primary immunodeficiency management, resulting in hospitalizations for pneumonia and sepsis. A trial of recombinant human C1-INH 4200 U was administered intravenously over approximately 5 min, 1 h prior to SCIG 1 g (Day 1). This dose was well tolerated with minimal AEs reported. SCIG 3 g was administered on Days 2 and 3 with no AEs reported. By continuing routine recombinant human C1-INH 4200 U prophylaxis, the patient was able to tolerate the recommended dose of SCIG 20 g once weekly without the debilitating neuropathy and other AEs previously experienced with SCIG alone. This case suggests that a patient with IRT-related AEs may benefit from C1-INH replacement therapy prior to SCIG/IVIG administration to improve tolerability.

PMID:41659931 | PMC:PMC12875838 | DOI:10.1002/ccr3.71988

Clin Case Rep. 2026 Feb 4;14(2):e71980. doi: 10.1002/ccr3.71980. eCollection 2026 Feb.

ABSTRACT

Hyperimmunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder characterized by eczema, recurrent staphylococcal infections, and significantly elevated serum IgE levels. An 18-year-old female presented with acute abdominal pain and was diagnosed with a retroperitoneal abscess. She had a history of recurrent skin abscesses, otitis media, and eczema since infancy, skeletal fractures, and retained primary teeth. Laboratory findings showed a serum IgE level above 20,150 U/L and a CRP of 180.30 mg/L. Methicillin-sensitive Staphylococcus aureus was cultured from the abscess drainage. The NIH-HIES score was 60 points. Genetic testing identified a heterozygous STAT3 variant (NM_139276.3: c.1145G>A, p.(Arg382Gln)), confirming autosomal-dominant HIES. This rare clinical presentation emphasizes the importance of considering HIES, even when deep-seated infections develop outside typical cutaneous or pulmonary sites.

PMID:41659947 | PMC:PMC12872590 | DOI:10.1002/ccr3.71980

Pediatr Int. 2026 Jan-Dec;68(1):e70330. doi: 10.1111/ped.70330.

ABSTRACT

BACKGROUND: Ataxia-telangiectasia (AT) is a rare disorder leading to multisystem involvement due to impaired DNA repair. Recent advances in targeted therapies highlight the importance of early diagnosis. This study aimed to evaluate clinical, radiological, and genetic variability in patients with AT and examine genotype-phenotype associations and diagnostic timing.

METHODS: A retrospective study was conducted on genetically confirmed AT patients followed in four pediatric neurology centers in Türkiye over a 12-year period.

RESULTS: A total of 21 patients with AT were included; the median age at symptom onset was 26 months, and the median age at diagnosis was 60 months, with a diagnostic delay of 21 months. Ocular telangiectasia was present in all patients. Ataxia, oculomotor apraxia, and dysarthria were other common features. Involuntary movements and strabismus were each observed in 52.4%. Cerebellar atrophy was noted in 57.1%, and decreased immunoglobulin levels in 95.2%. No significant differences in the frequency of clinical findings were observed between early and late diagnosis groups, except that recurrent respiratory tract infections were significantly more common in the early-diagnosis group (p = 0.035).

CONCLUSION: In this study, clinical variability and key clinical features of AT were identified. AT should be suspected and immunoglobulin levels assessed in patients with neurological symptoms and recurrent infections. Improving recognition of AT may contribute to earlier diagnosis and better outcomes.

PMID:41660796 | DOI:10.1111/ped.70330

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