Manish Butte

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

Clin Chest Med. 2025 Mar;46(1):61-75. doi: 10.1016/j.ccm.2024.10.005. Epub 2024 Nov 29.

ABSTRACT

This review of immunocompromised host pneumonia as the result of inborn errors of immunity (IEI) is organized by opportunistic pulmonary pathogen. The authors identify patients who warrant an evaluation for an IEI based on their clinical presentation. Their recommendations are guided by the immune defect(s) associated with each opportunistic pulmonary infection. Physicians without expertise in immunology may begin an evaluation for IEI using the guidance provided here. Comprehensive evaluation by an immunologist may also be warranted in many instances.

PMID:39890293 | DOI:10.1016/j.ccm.2024.10.005

Pediatr Infect Dis J. 2025 Jan 30. doi: 10.1097/INF.0000000000004737. Online ahead of print.

ABSTRACT

INTRODUCTION: Listeria monocytogenes is a Gram-positive bacillus that causes severe infections mainly in newborns, pregnant women, immunocompromised individuals, and elderly. In this report, we present a case of immune dysregulation that presented with invasive Listeria infection despite the absence of these risk factors.

CASE: A previously healthy 5-year-old girl developed L. monocytogenes meningitis, which is unusual given her age and lack of typical risk factors. The patient initially presented with fever, diarrhea and altered mental status, unresponsive to empiric antibiotic treatment. Besides clinical diagnosis of meningitis, laboratory tests revealed pleocytosis and positive polymerase chain reaction test for L. monocytogenes in cerebrospinal fluid. Despite initial improvement, the patient developed proteinuria and hypertension and was later diagnosed with focal class 3 lupus nephritis following a renal biopsy. Given the atypical nature of her L. monocytogenes infection, persistent organomegaly, and lupus nephritis, further immunological evaluation was conducted. Genetic testing revealed a de-novo gain-of-function mutation in the PIK3CD gene, confirming the diagnosis of Activated Phosphoinositide 3-Kinase Delta Syndrome 1 (APDS1), a rare primary immunodeficiency characterized by lymphoproliferation and autoimmunity. The patient was started on immunoglobulin replacement therapy and prophylactic trimethoprim-sulfamethoxazole. No recurrence of severe infection occurred during 2 years of follow-up.

CONCLUSION: This case underscores the importance of considering underlying immune dysregulations in pediatric patients with atypical presentation of Listeria infections.

PMID:39889727 | DOI:10.1097/INF.0000000000004737

Mol Med Rep. 2025 Mar;31(3):81. doi: 10.3892/mmr.2025.13446. Epub 2025 Jan 31.

ABSTRACT

Cartilage‑hair hypoplasia (CHH) is an autosomal recessive form of metaphyseal chondrodysplasia caused by RNA component of mitochondrial RNA processing endoribonuclease (RMRP) gene variants; however, its molecular etiology remains unclear. Whole‑exome sequencing was performed to detect possible pathogenic variants in a patient with a typical short stature and sparse hair. A co‑segregation analysis was also conducted and variants in the family members of the patient were confirmed by Sanger sequencing. A novel compound heterozygous variant in RMRP (NR_003051.4: n.‑21_‑2dup and n.197C>T) was identified in the affected patient. Data from 2 years and 4 months of follow‑up showed a positive effect of growth hormone (GH) therapy on height. Subsequently, two gene expression profiles associated with CHH were obtained from the EMBL‑EBI ENA and ArrayExpress databases. Differentially expressed genes between patients with CHH and healthy controls were selected using R software and were subjected to core analysis using ingenuity pathway analysis (IPA) software. IPA core analysis showed that the ‘cell cycle checkpoints’ was the most prominent canonical pathway, and the top enriched diseases and functions included various types of cancer, immunological diseases, development disorders and respiratory diseases. The integrative analysis displayed that RMRP can regulate the aberrant expression of downstream targets mainly via the transcription factor TP53, which results in the inhibition of ‘cell cycle checkpoints’; eventually, functions associated with the CHH phenotype, such as ‘growth failure or short stature’ are activated. In conclusion, novel disease‑causing genetic variants of RMRP expand the genetic etiology of CHH, which must be clinically differentiated from achondroplasia. The findings of the present study provide new insights into the mechanisms underlying CHH.

PMID:39886981 | DOI:10.3892/mmr.2025.13446

Pan Afr Med J. 2024 Oct 11;49:33. doi: 10.11604/pamj.2024.49.33.42418. eCollection 2024.

ABSTRACT

Hyper immunoglobulin M (IgM) syndromes are a collection of uncommon primary combined immunodeficiency disorders. They are characterized by recurrent bacterial infections due to low levels of IgG, IgA, and IgE, while IgM levels remain normal or high. These conditions stem from a mutation in the CD40 ligand gene or disruptions in the CD40-signaling pathway. Those affected face increased susceptibility to frequent bacterial infections, an elevated likelihood of autoimmune issues, and early-onset malignancies. These syndromes are rare and account for a small fraction of immunodeficiency cases. We describe a case of an African infant, who had a prolonged pediatric intensive care unit admission due to recurrent and severe infections which took a prolonged course of medication to be treated. After a diagnostic workup, a diagnosis of X-linked hyper IgM syndrome was established, and currently, our child is on monthly replacement of IV immunoglobulin and daily prophylactic cotrimoxazole tablets. Early diagnosis of primary immunodeficiency disorders reduces the incidence of infections and the severity of complications. This case demonstrates the consequences of delayed diagnosis and resulting in a prolonged hospital stay.

PMID:39886113 | PMC:PMC11781210 | DOI:10.11604/pamj.2024.49.33.42418

Leuk Lymphoma. 2025 Jan 28:1-15. doi: 10.1080/10428194.2025.2456970. Online ahead of print.

ABSTRACT

Over the past two decades, there has been a continuous improvement in outcome for patients with indolent lymphoma (iNHL) resulting in a gradual accumulation of survivors. While life expectancy in the current era approaches that of the lymphoma-free population, patients continue to experience lifelong complications of the disease and its treatment affecting general health, emotional, psychological and social wellbeing, relationships, employment, finances, and fitness. Contemporary care models while suited to the management of lymphoma are often lacking when it comes to identification and management of these additional needs. Given improvements in physical survival achieved over the past decades, it is timely for us to focus on other issues affecting patient wellbeing including immunodeficiency and infection, second cancers, cardiovascular disease, bone health, psychological wellbeing, and sexual health. Many of these aspects are in the domain of the primary care physician; however, there is limited guidance on how these issues should be addressed. It is now time for us to engage our patients, their caregivers, and other healthcare providers in care aspects beyond the lymphoma diagnosis, so they can anticipate a rich and full life, free from both direct and indirect consequences of the lymphoma diagnosis.

PMID:39876569 | DOI:10.1080/10428194.2025.2456970