Research

Lab Invest. 2025 Apr 6:104163. doi: 10.1016/j.labinv.2025.104163. Online ahead of print.

ABSTRACT

Selective IgA deficiency (sIgAD) is the most common type of primary immunodeficiency. The diagnosis of sIgAD has occasionally been suggested when a complete absence of background IgA immunofluorescent staining on renal biopsies was observed, but such findings have been described in only two patients to date. In this study, the clinical, demographic, and renal biopsy findings of 15 patients with suspected sIgAD, based on a total lack of immunofluorescence for IgA, were collected. In our cohort, most patients presented with acute kidney injury, with or without proteinuria, and had clinical histories consistent with sIgAD, including recurrent infections, autoimmune diseases, allergic disorders, and cancer. However, only one patient had a known history of sIgAD. Immunoglobulin testing was available in 10 out of 15 patients, nine of whom showed findings consistent with a diagnosis of sIgAD. Renal biopsies in most patients revealed immune-related glomerular diseases, with lupus nephritis being the most common diagnosis. Recognizing the total absence of IgA staining indicative of sIgAD is important, as it can be associated with recurrent infections, autoimmune diseases, allergic disorders, anaphylactic transfusion reactions, and rarely, malignancies.

PMID:40199423 | DOI:10.1016/j.labinv.2025.104163

Arch Pediatr. 2025 Apr 7:S0929-693X(25)00055-7. doi: 10.1016/j.arcped.2025.01.008. Online ahead of print.

ABSTRACT

BACKGROUND: Intravenous immunoglobulin G (IVIg) is used as a replacement therapy in primary immunodeficiency disorders (PIDs). Although IVIg is generally accepted as a safe treatment, the incidence of adverse events (AEs), most of which are mild and transient, varies between 1 % and 81 %. The aim of this study was to determine the adverse effects and influencing factors associated with IVIg replacement therapy in pediatric patients with PID.

MATERIALS AND METHODS: Children with PID who received IVIg replacement therapy between January 1, 2012 and December 31, 2021, at Dr. Sami Ulus Children’s Hospital were included in our study.

RESULTS: Overall, 69 (52 male, 17 female) patients who received a total of 2,025 IVIg infusions were evaluated. AEs were observed in 40.6 % of the patients and in 8.9 % of the infusions. All AEs encountered in the study were mild to moderate. Immediate-onset AEs were observed in 3.5 % of the infusions and delayed-onset AEs in 5.4 %. Late-onset AEs were not observed. The most commonly observed AEs were headache (n = 50, 2.5 %), fever (n = 37, 1.8 %), and malaise (n = 19, 0.9 %). The most common immediate AE was fever (n = 28, 1.4 %), while the most common delayed AE was headache (n = 44, 2.2 %).

CONCLUSION: AEs encountered in patients with PID receiving IVIg infusions are mild to moderate. Pediatric patients should be followed up for delayed AEs by contacting their families after the infusion is completed and should be questioned before the next infusion. IVIg replacement is a safe treatment when given with an appropriate premedication and infusion rate.

PMID:40199691 | DOI:10.1016/j.arcped.2025.01.008

J Dermatol. 2025 Apr 9. doi: 10.1111/1346-8138.17733. Online ahead of print.

ABSTRACT

Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome is a rare immunodeficiency caused by gain-of-function mutations in the chemokine receptor CXCR4. While human papillomavirus (HPV) skin infection (warts) is the dermatological hallmark of the disease, individuals with WHIM have high rates of other skin manifestations that may aid early diagnosis and management. This study was a retrospective review of medical records from a United States National Institutes of Health natural history cohort of patients with WHIM syndrome seen between 2005 and 2024, including a cross-sectional analysis of cutaneous manifestations and CXCR4 variants. The cohort compromised 45 patients with genetically confirmed WHIM syndrome, 16 men and 29 women, with a mean age of 33.3 years (range, 0-69 years) and mean age at diagnosis of 20.4 years (range, 0-59 years). The cohort exhibited a range of skin manifestations which included cutaneous infections with HPV in 34 (76%) patients, bacteria in 32 (71%) patients, other viruses in 27 (60%) patients, and fungi in 25 (56%) patients. Inflammatory conditions included six (13%) patients with seborrheic dermatitis, five (11%) with contact dermatitis, four (9%) with psoriasis, three (7%) with nummular eczema, and 13 (29%) with other eczematous dermatitis. Despite the young median age, seven (16%) patients had skin cancer. All seven patients had CXCR4 truncation mutations, while those with a missense mutation (E343K) generally had fewer skin manifestations. Our study found that WHIM syndrome is associated with diverse infectious, inflammatory, and neoplastic skin conditions beyond HPV skin infection.

PMID:40202253 | DOI:10.1111/1346-8138.17733

Medicina (B Aires). 2025;85(2):376-387.

ABSTRACT

Hereditary angioedema (HAE) is a rare autosomal dominant disease, characterized by episodes of edema involving the skin, gastrointestinal tract and larynx. HAE has a 15% to 50% historical asphyxia mortality. It is the consequence of C1 inhibitor deficiency. The identification of bradykinin as the principal mediator of the disease has led to the development of new drugs for the treatment of HAE. HAE treatment is agreed in international consensus. A therapeutic guide for the treatment of the disease was published in Medicina (Buenos Aires) in 2012, but new and relevant diagnostic and therapeutic advances have been described subsequently. We here update the pharmacology of new drugs available for the treatment of HAE in Argentina, as well as briefly describe the new forms of the disease.

PMID:40198173

Arch Dermatol Res. 2025 Apr 7;317(1):681. doi: 10.1007/s00403-025-04206-x.

ABSTRACT

Leukocyte adhesion deficiency (LAD) is a group of inborn errors of immunity caused by mutations of integrin subunit b2 gene (ITGB2). Pyoderma gangrenosum (PG) is an uncommon neutrophilic dermatosis characterized by recurrent, sterile, and enlarging necrotic ulcers which may manifest as a single or multiple new lesions simultaneously. Here we report a 43-year-old woman from a consanguine marriage who was diagnosed with LAD-I in childhood, recurrent severe PG-like lesion, and atypical manifestations including celiac disease and low CD19 B-cell subsets. A targeted genetic panel revealed a novel homozygous missense variant c.988T>C (Tyr330His) in ITGB2 gene. While the treatment with prednisolone, cyclosporine, and antibiotics led to partial improvement, the patient unfortunately discontinued the therapy and later died from septicemia. Early hematopoietic cell transplantation (HCT) shortly after birth can be highly effective in managing patients with LAD and preventing life-threatening infections. However, evidence suggests that HCT does not prevent autoinflammatory and autoimmune disorders such as PG. Therefore, it is important to monitor LAD patients for the potential development of PG, even after HCT.

PMID:40195196 | DOI:10.1007/s00403-025-04206-x

Cureus. 2025 Apr 7;17(4):e81827. doi: 10.7759/cureus.81827. eCollection 2025 Apr.

ABSTRACT

Complement factor I (CFI) deficiency is a rare primary immunodeficiency that disrupts the classical and alternative complement pathways, potentially causing severe recurrent infections and autoimmune manifestations in pediatric patients. However, the coexistence of both pathways in a pediatric patient is extremely uncommon. We report a seven-year-old patient with a rare primary immunodeficiency disorder who presented with recurrent middle ear infections, paronychia, gastrointestinal infections, and respiratory infections. Genetic testing revealed a previously unreported homozygous variant in the CFI gene (c.848A>G; p.D283G). Immunological testing showed a decrease in complement C3, CFI, and CFH levels in the patient. Interestingly, the patient presented with IgA vasculitis, with renal pathology showing deposits of immune complexes containing IgA, IgG, IgM, and C1q. By considering the child’s condition and genetic test results, the child was treated symptomatically and received regular peritoneal dialysis treatment. Subsequently, the child’s condition improved compared to before and was discharged from the hospital. This case highlights the importance of considering CFI deficiency in children with recurrent infections and abnormalities in both the classical and alternative complement pathways. Our findings expand the known phenotypic spectrum of CFI deficiency and contribute to understanding genotype-phenotype correlations in complement disorders.

PMID:40196760 | PMC:PMC11975128 | DOI:10.7759/cureus.81827

Clin Immunol. 2025 Apr 2:110491. doi: 10.1016/j.clim.2025.110491. Online ahead of print.

ABSTRACT

BACKGROUND: Neutralizing autoantibodies against type I interferons were strongly linked to severe COVID-19 in unvaccinated patients; however, this has yet to be evaluated in vaccinated individuals.

OBJECTIVE: To analyze how these autoantibodies influences disease variability in vaccine breakthrough COVID-19 pneumonia patients.

METHODS: Clinical and laboratory data; autoantibodies blocking interferon-α2 and -ω; and humoral response to SARS-CoV-2 vaccine were collected from all vaccinated COVID-19 pneumonia patients admitted from April 2021 to December 2022 at Bellvitge University Hospital, Spain.

RESULTS: 458 patients developed COVID-19 pneumonia despite an appropriate antibody response to SARS-CoV-2 vaccination. Autoantibodies neutralizing interferons were significantly more prevalent in patients with critical pneumonia compared to those with milder forms (8.8 % vs. 3.6 %; p = 0.037). Having these autoantibodies was an independent predictor for critical COVID-19 pneumonia (OR 2.88 [95 %CI 1.18-6.98]).

CONCLUSION: Vaccination considerably reduces the severity of COVID-19; however, patients with type I interferon autoantibodies remain at increased risk of severe disease.

PMID:40185298 | DOI:10.1016/j.clim.2025.110491

Front Immunol. 2025 Mar 20;16:1528414. doi: 10.3389/fimmu.2025.1528414. eCollection 2025.

ABSTRACT

Subcutaneous (SCIG) and intravenous immunoglobulin (IVIG) replacement are both used to prevent infections in patients with secondary immunodeficiency (SID). Compared with IVIG, SCIG has fewer systemic side effects and, additionally, facilitates home-based treatment. Shared decision-making practice should include discussion of aspects such as patient preference as well as the associated risks and benefits of treatment. We review the available evidence for the use of SCIG treatment in patients with SID, focusing on patient-reported outcomes (PROs). In most studies, there were improvements to health-related quality of life with SCIG treatment, compared with before initiating SCIG without prior IVIG treatment, or after switching to SCIG from IVIG treatment, or a no-SCIG/IVIG cohort. Treatment satisfaction with SCIG was similar between patients with SID and primary immunodeficiency disease. Patient preference and perception assessments highlighted the benefits of SCIG compared with IVIG, such as ease of use and administration, convenience, and time-effectiveness. In addition, many patients self-administered SCIG at home. Such aspects may be of specific benefit to patients with SID and hematological malignancy by reducing the risk of infection exposure in clinical settings. PRO data may be useful during shared decision-making discussions with patients with SID.

PMID:40181959 | PMC:PMC11967276 | DOI:10.3389/fimmu.2025.1528414

Front Pediatr. 2025 Mar 13;13:1553984. doi: 10.3389/fped.2025.1553984. eCollection 2025.

ABSTRACT

Down Syndrome (DS), or Trisomy 21, is a common inherited chromosomal disorder, caused by an extra copy of chromosome 21, with features including intellectual disability, hearing and vision disorders, hypotonia, hypothyroidism, cardiac and gastrointestinal structural abnormalities. The characteristic features of flattened nasal bridge, mandibular and maxillary hypoplasia, relative macroglossia, and a narrow nasopharyngeal region all predispose to airway complications and structural abnormalities can extend to the lower airways and lung parenchyma. Congenital airway stenoses and malacia are present in around 1.5% children with DS and in 20% of these, there are multiple anomalies. Structural lung abnormalities include reduced alveolar numbers and altered lung architecture. The prevalence of pulmonary hypertension is a significantly increased, estimated to affect 5-10%, and increases if congenital or gastrointestinal co-morbidities are also present. The association of DS with hypotonia, increased oral secretions, gastrointestinal reflux and aspiration and obesity increase the morbidity associated with these anatomical variants contributing to poor airway clearance and increased risk of respiratory tract infections. In addition, it is been recognised that the increased risk of infections (particularly of the respiratory tract) as well as autoimmune disorders and haematological malignancies suggest a level of immunodeficiency and immune dysregulation. The anatomical features of DS predispose children to the development of sleep disordered breathing (SDB) in addition to adenotonsillar hypertrophy, the primary cause in children. Treatment options include surgery, non-invasive ventilation, and anti-inflammatory medications. Emerging techniques include drug-induced sleep endoscopy (DISE), a useful tool for assessment of the upper airway in children with OSA and to identify the additional sites of airway obstruction that may be present in DS and hypoglossal nerve stimulation for individuals resistant other treatments.

PMID:40182002 | PMC:PMC11966059 | DOI:10.3389/fped.2025.1553984

Endocr Metab Immune Disord Drug Targets. 2025 Apr 3. doi: 10.2174/0118715303363026250312063731. Online ahead of print.

ABSTRACT

BACKGROUND: Inborn errors of immunity (IEI) include immunodeficiencies affecting cellular and humoral immunity.

OBJECTIVES: We aimed to compare the effectiveness of the LTT and carboxyfluorescein succinimidyl ester (CFSE) assays in assessing lymphocyte proliferation in IEI patients.

METHODS: We utilized radioactive [3H]-thymidine and non-radioactive CFSE to measure lymphocyte proliferation in three distinct groups: syndromic CID (SyCID), non-syndromic combined immunodeficiency (N-SyCID), and primary antibody deficiency (PAD).

RESULTS: LTT identified 8 cases of abnormal lymphocyte proliferation among all patients, whereas CFSE detected 23 cases. In the N-SyCID group, LTT identified more abnormalities than CFSE, whereas, in the SyCID and PAD groups, CFSE detected more defects. Two patients with ataxia telangiectasia and CVID had positive results on both LTT and CFSE tests, and a specific ORAI1 gene mutation resulted in differing test outcomes.

CONCLUSION: It was found that the CFSE method is a reliable and practical choice for measuring mitogenic T-cell responses in unclassified IEI patients for confirmation of immunologic diagnosis.

PMID:40183264 | DOI:10.2174/0118715303363026250312063731