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J Clin Immunol. 2025 Feb 7;45(1):72. doi: 10.1007/s10875-025-01865-3.

NO ABSTRACT

PMID:39918595 | DOI:10.1007/s10875-025-01865-3

Front Immunol. 2025 Jan 23;16:1517347. doi: 10.3389/fimmu.2025.1517347. eCollection 2025.

ABSTRACT

Wiskott-Aldrich syndrome (WAS) (MIM #301000) is a rare X-linked primary immunodeficiency due to mutations in the WAS gene, characterized by thrombocytopenia with small platelets, eczema, recurrent infections, and an increased incidence of autoimmunity and malignancies. A wide spectrum of mutations has been identified in the WAS gene responsible for a broad variety of clinical phenotypes. By using targeted next-generation sequencing (t-NGS), we identified in a 2-month-old boy with thrombocytopenia and immunological alterations a 4-nucleotide deletion from position +3 to +6 of intron 8 (c.777 + 3_777 + 6delGAGT) of WAS, currently classified on ClinVar as a variant of uncertain significance. The in-vitro characterization of the variant revealed the complete retention of intron 8 in the mature transcript, suggesting a splicing defect due to the loss of a splice donor site at the 5′-end of intron 8. By sequencing the polymerase chain reaction product, we identified a premature stop at codon 269; thus, consequently, no Wiskott-Aldrich syndrome protein (WASp) was detectable in peripheral blood mononuclear cells from the patient. Due to the total absence of a full-length WASp, it is expected that the patient will develop the severe form of the disease, although further monitoring is needed to better define his phenotype.

PMID:39917307 | PMC:PMC11798879 | DOI:10.3389/fimmu.2025.1517347

J Allergy Clin Immunol. 2025 Feb 4:S0091-6749(25)00119-8. doi: 10.1016/j.jaci.2025.01.030. Online ahead of print.

ABSTRACT

BACKGROUND: Natural killer (NK) cell deficiency (NKD) is an immunodeficiency phenotype in which abnormality of NK cells is the major clinically relevant immune defect.

OBJECTIVE: We sought to define the clinical, immunologic and genetic characteristics of patients with NKD to aid in the understanding of these individuals and this cell type, and guide future research and clinical practice.

METHODS: During 2006-2022, 168 individuals suspected of having NKD were enrolled, with comprehensive clinical, immunological and genetic data collected and analyzed. Research exome sequencing was performed to identify both known and novel genetic associations.

RESULTS: NK cell abnormalities consistent with NKD were confirmed in 148 individuals. Most presented during childhood (median age 13y, range 0-76y), though 34% were adults. All tested individuals exhibited reduced NK cell cytotoxic function; 44% also had decreased NK cell numbers and/or mature NK cells. Herpesvirus and/or papillomavirus infections were observed in 71%, malignancies in 7%, and a 5% case-fatality rate was noted. Among the 99 individuals who underwent research exome sequencing, 29% were considered solved for a likely contributing variant allele, 52% of these cases involving known genes and 48% involving novel genes.

CONCLUSIONS: NKD is a phenotypic immunodeficiency associated with increased susceptibility to certain viral infections and cancer, with multiple genetic etiologies, revealing key biological pathways for NK cell development and function. This research underscores the role of NK cells in human immune defenses, and helps advance the identification of at-risk populations, precise genetic diagnoses, and informed clinical management for those with NKD.

PMID:39914554 | DOI:10.1016/j.jaci.2025.01.030

Hematol Oncol. 2025 Mar;43(2):e70035. doi: 10.1002/hon.70035.

ABSTRACT

Primary lymphoma of the female genital tract (PLFGT) is a rare disease. The incidence is gradually increasing each year. There have been few reports about PLFGT, and most of them have involved individual cases and small-sample retrospective analyses. The pathogenesis of PLFGT is still under exploration and may be associated with hormones, inflammation/infection, and immunodeficiency. Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type. The majority of the patients presented with vaginal bleeding, abdominal pain, an abdominal mass, and other nonspecific symptoms. Lymphoma-associated B symptoms are quite rare. These patients initially visited gynecological departments, possibly leading to misdiagnosis due to nonspecific features. The treatment strategies for and prognosis of PLFGT differ substantially from those of other gynecologic malignancies. Thus, interdisciplinary cooperation among gynecologists, pathologists, and hematologists is essential.

PMID:39912357 | DOI:10.1002/hon.70035

Pediatr Dermatol. 2025 Feb 5. doi: 10.1111/pde.15874. Online ahead of print.

ABSTRACT

Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disorder characterized by post-natal growth retardation, facial dysmorphism, large thumbs and halluces, and intellectual deficits. RTS has a broad phenotypic spectrum including cardiac, genitourinary, digestive, ear, nose and throat, and skin manifestations. Patients also have an increased risk of severe infections, developing benign tumors, and immunological abnormalities suggesting primary immunodeficiencies. We report a case of RTS with severe recalcitrant eczema, recurrent skin and chest infections, food allergies associated with a hyper-IgE profile, and other immunological abnormalities, who had a significant response to dupilumab.

PMID:39910735 | DOI:10.1111/pde.15874

Immunol Cell Biol. 2025 Feb 5. doi: 10.1111/imcb.12856. Online ahead of print.

ABSTRACT

In this article, we discuss a recent study, where autosomal monoallelic expression of genes underlying Inborn Errors of Immunity were investigated. About 2-10% of genes are predominantly transcribed from a single allele leading to autosomal random monoallelic expression (I). If this is skewed in a cell population from an individual with an autosomal dominant inborn error of immunity, this can lead to a mild to no phenotype (incomplete penetrance) if the wildtype allele is favored (II), or to more severe disease presentation if the variant allele is favored (III).

PMID:39909075 | DOI:10.1111/imcb.12856

Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb 5. doi: 10.1007/s00210-025-03852-2. Online ahead of print.

ABSTRACT

Vulvovaginal candidiasis (VVC) is one of the most common infections of the genital tract in women of reproductive age. In this umbrella review, we aim to summarize all the existing literature about different treatment strategies for vulvovaginal candidiasis. This umbrella review adhered to the PRISMA guidelines, systematically searching databases including Scopus, PubMed, and Web of Science for meta-analyses for assessing different treatment methods for vaginal candidiasis until September 2024. Data extraction focused on outcome metrics, and methodological quality assessed via the AMSTAR-2 checklist. In our study, we have included a total of five articles. Within pharmacological interventions, treating individuals with fluconazole, ketoconazole, clotrimazole, and oteseconazole has demonstrated a significant reduction in the risk of mycological recurrence at the 12-month mark. Moreover, women who were treated with fluconazole experienced fewer episodes of VVC recurrence immediately after treatment, as well as at the 3- and 6-month follow-up periods when compared to those who received a placebo. In terms of non-pharmacological interventions, the combination therapy involving Redcore lotion alongside miconazole exhibited more substantial results in decreasing episodes of VVC compared to miconazole used alone. Furthermore, our results revealed a negative correlation between probiotic consumption and the rate of recurrence. In the end, we examined the primary treatment methods for vulvovaginal candidiasis and highlighted that, apart from azoles and antibiotics, emerging treatments such as probiotics and Redcore, along with certain established antibiotics, can also be considered viable options. More studies are needed to find more effective treatments as well as treatments for specific conditions such as pregnancy or immunodeficiency.

PMID:39907782 | DOI:10.1007/s00210-025-03852-2

Lancet Reg Health Southeast Asia. 2025 Jan 21;33:100531. doi: 10.1016/j.lansea.2025.100531. eCollection 2025 Feb.

ABSTRACT

BACKGROUND: The transmission of wild poliovirus (WPV1) and circulating vaccine-derived poliovirus (cVDPV) continues to be a major Public Health Emergency of International Concern. Currently, only Afghanistan and Pakistan remain polio-endemic for WPV1. In response to the co-circulation of VDPV2 with WPV1, the Technical Advisory Group of WHO had recommended two nationwide campaigns of trivalent oral poliovirus vaccine (tOPV) for children aged <5 years in Pakistan in 2020. We assessed the humoral and mucosal immune responses in children who received two doses of tOPV (during vaccination campaigns) in Karachi, Pakistan.

METHODS: A cross-sectional survey was conducted in four peri-urban sites (Cattle Colony, Ibrahim Hyderi, Ali Akber Shah, Rehri Goth) Karachi, Pakistan. Venous blood samples from children aged between 1 month and 5 years were obtained. Children who were acutely ill, requiring hospitalisation, with primary immunodeficiency, or with a chronic medical illness, were excluded from the study. Stool and serum testing was performed at the National Institute of Health, Pakistan. Sera samples were analysed using microneutralization assays to quantify polio antibodies for all three serotypes: type 1, 2, and 3. The stool samples collected at baseline, 7, 14, and 28 days (after each tOPV dose) were tested for the presence of poliovirus.

FINDINGS: Of 285 eligible children, 225 had received both tOPV doses and provided three analysable blood samples, and 193 children provided seven viable stool samples. The seroconversion rate for type 2 was 72% (44/61, 95% CI: 59.8-81.8) after the first tOPV dose; cumulative seroconversion after two doses was 93.4% (95% CI: 84.3-97.4). Seven days after the first and second tOPV campaigns, 32.7% and 18.6% excreted Sabin (vaccine) poliovirus type 2, respectively.

INTERPRETATION: The study demonstrated enhanced mucosal immunity as well as a high type 2 seroconversion rate and antibody seroprevalence after two tOPV campaigns.

FUNDING: WHO, Geneva, Switzerland.

PMID:39902295 | PMC:PMC11788853 | DOI:10.1016/j.lansea.2025.100531

Int J Mol Cell Med. 2024;13(4):361-373. doi: 10.22088/IJMCM.BUMS.13.4.361.

ABSTRACT

Diffuse Large B-cell Lymphoma (DLBCL), the most common type of primary central nervous system lymphoma (PCNSL), is a rare aggressive subtype of DLBCL with a poorly understood biology. This study aimed to investigate the prevalence of O-6-Methylguanine-DNA Methyltransferase (MGMT), C-MYC and Epstein-Barr virus Encoded RNA (EBER) positivity in CNS-DLBCLs. Using tissue microarray method, formalin-fixed paraffin-embedded blocks of 76 cases of confirmed PCNS-DLBCL and 2 cases of immunodeficiency-related CNS DLBCL were examined for EBER and C-MYC by chromogenic in situ hybridization (CISH), and for MGMT, CD10, BCL2, BCL6, MUM1 and Ki67 by Immunohistochemistry (IHC). The results were analyzed in association with histopathologic and demographic characteristics. The majority of the tumors were of non-germinal center B-cell (non-GCB) type. Loss of MGMT expression on IHC, as a surrogate marker of MGMT methylation, was detected in about 68.9% of PCNSLs. Preserved MGMT expression was found to occur more frequently in males and in MUM1-negative and GCB-type tumors. EBER positivity was exclusively seen in immunodeficient cases. Low C-MYC amplification was detected in 18% of cases and showed association with BCL2 and Ki67 expression. We concluded that loss of MGMT expression is a common phenomenon in PCNSLs. Epstein-Barr virus (EBV) may not be commonly detected in PCNS-DLBCL as frequently as in systemic DLBCL, but its expression is inevitable in CNS-DLBCLs of immunocompromised ones. Maintained MGMT expression is associated with less aggressive histopathologic features. Further studies are warranted to confirm the prognostic significance of loss of MGMT expression in PCNSLs and its potential use for predicting therapeutic response to alkylating agents in PCNSLs.

PMID:39895917 | PMC:PMC11786121 | DOI:10.22088/IJMCM.BUMS.13.4.361

Orphanet J Rare Dis. 2025 Feb 1;20(1):47. doi: 10.1186/s13023-025-03562-1.

ABSTRACT

BACKGROUND: Patients with hereditary angioedema (HAE) experience recurrent, unpredictable episodes of edema. These swellings are often preceded by prodromal symptoms. HAE management includes acute treatment, long-term prophylaxis (LTP), and short-term prophylaxis (STP) before procedures with a risk of swelling. The effects of LTP on prodromal symptoms and the necessity for STP in patients on LTP remain unclear.

METHODS: A questionnaire-based study involving HAE and AAE patients receiving LTP was conducted. Changes in prodromal symptoms and the incidence of procedures with an increased risk of swelling, including surgeries, dental procedures, and endoscopies were assessed.

RESULTS: A total of 26 patients were included in the study. Among them, 18 experienced zero to three attacks since starting LTP. Abdominal attacks constituted 60% of all attacks, followed by swellings of the extremities and head and neck. The most frequently reported trigger factors were stress and mechanical stimuli, followed by infections. 9 patients reported surgical procedures, with 8 using STP. Of these, 4 experienced breakthrough attacks, including one laryngeal attack. 105 dental procedures were reported, with STP used for only one. Only one angioedema attack occurred after an intervention without STP. For endoscopies, 7 procedures were reported, 3 of which were performed under STP. Two abdominal attacks were reported by the same patient, both without prior STP. Prodromal symptoms remained consistent in type but varied in intensity and frequency under LTP.

CONCLUSIONS: For dental procedures, the mandatory use of STP in HAE patients on effective LTP should be reconsidered, provided acute treatment is available and other trigger factors are absent.

PMID:39893484 | DOI:10.1186/s13023-025-03562-1