Manish Butte

Respir Med Case Rep. 2025 Apr 19;55:102214. doi: 10.1016/j.rmcr.2025.102214. eCollection 2025.

ABSTRACT

We report three cases of bronchiectasis caused by homozygous WFDC2 variants. The ages at diagnosis of bronchiectasis were 18, 24, and 16 years, and all patients had a history of chronic sinusitis since childhood. Despite low nasal nitric oxide levels, the radiologic features resembled those of cystic fibrosis, characterized by bronchiectasis predominantly in the upper lobes. All patients experienced frequent exacerbations and respiratory dysfunction, even with long-term macrolide therapy. Consequently, two of the three patients required lung transplantation. Considering the possibility of founder mutations, WFDC2 variants should be included in diagnostic panels for patients with sinopulmonary disease in Asian populations.

PMID:40401042 | PMC:PMC12093231 | DOI:10.1016/j.rmcr.2025.102214

Curr Opin Pulm Med. 2025 May 22. doi: 10.1097/MCP.0000000000001180. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Median survival after lung transplantation is 5.7 years, which lags behind other solid organ transplants, such as heart, liver, and kidney. The major barrier to long-term survival in lung transplant recipients is chronic lung allograft dysfunction (CLAD). This review discusses the challenge of CLAD as a barrier to tolerance and identifies key areas in the field that require further development.

RECENT FINDINGS: CLAD is a heterogenous disease in its kinetics of onset and severity and remains a clinical diagnosis of exclusion, based on a decline in allograft function. While acute cellular rejection and antibody-mediated rejection are major risk-factors for CLAD, other barriers to long-term allograft acceptance are aspiration and primary graft dysfunction. However infections, particularly respiratory viral infections and Cytomegalovirus (CMV) remain the most significant risks for CLAD. Additionally, the lung transplant field is limited by a lack of molecular diagnostic assays for CLAD. Further, new targets are needed for precision immunosuppression, and more studies are needed to develop novel interventions to extend allograft acceptance.

SUMMARY: This review discusses new lines of study to address important unmet needs necessary to extend lung allograft acceptance. Other studies, such as tandem lung transplant and bone marrow transplant in select patients with primary immunodeficiency may provide additional lessons on how to potentially establish tolerance. However, tolerance in lung transplant is extremely rare, and further studies are needed to pursue this ultimate goal.

PMID:40396535 | DOI:10.1097/MCP.0000000000001180

AIDS Rev. 2025;27(1):1-8. doi: 10.24875/AIDSRev.24000012.

ABSTRACT

Many non-infectious diseases have as a common complication the secondary development of infections, which are most likely to occur in immunocompromised individuals. Immunodeficiency (ID) is classified into primary and secondary ID (SID). Primary ID results from fundamental defects in proteins and cells that are critical for specific immune responses. Extrinsic factors, such as long-term use of immunosuppressive drugs and chronic diseases, can also affect immune responses, leading to a state of SID. In this review, we summarized the spectra of potential infectious pathogens in primary and SID, which are very different from those in immunocompetent individuals. We hope that this review will help clinicians with empirical management of infections in immunocompromised individuals caused by different etiologies and lead to better patient outcomes.

PMID:40393059 | DOI:10.24875/AIDSRev.24000012

Front Immunol. 2025 May 5;16:1572791. doi: 10.3389/fimmu.2025.1572791. eCollection 2025.

ABSTRACT

Hyper IgM syndrome (HIGM) is a rare immunodeficiency caused by impaired immunoglobulin class switching, leading to recurrent infections. The present report describes the case of an 18-year-old man initially diagnosed with common variable immunodeficiency at 3 years of age. Genetic analysis revealed a hemizygous CD40LG missense variant (p.Arg203Ile) associated with X-linked HIGM (XHIGM). Structural and flow cytometric analyses indicated normal CD40 ligand (CD40L) expression on activated CD4⁺ T-cells but impaired CD40 binding, indicating disrupted immune signaling. Notably, the patient experienced neither bacterial infections requiring hospitalization nor opportunistic infections during 15 years of immunoglobulin replacement therapy. These findings indicate that the p.Arg203Ile variant destabilizes CD40L-CD40 interactions without affecting CD40L expression, suggesting a hypomorphic phenotype. This report highlights the importance of combining genetic testing with functional analysis when evaluating atypical XHIGM presentations to predict clinical severity and provide a scientific basis for personalized treatment strategies. Additional studies are required to assess the long-term outcomes and potential curative therapies for similar cases.

PMID:40391217 | PMC:PMC12086146 | DOI:10.3389/fimmu.2025.1572791

Front Endocrinol (Lausanne). 2025 May 5;16:1559281. doi: 10.3389/fendo.2025.1559281. eCollection 2025.

ABSTRACT

BACKGROUND: A defective thyroid-stimulating hormone receptor (TSHR) gene is one of the main known genetic factors leading to congenital hypothyroidism (CH). However, the relationship between TSHR genotypes and phenotype and the underlying reason for the broad spectrum of phenotypes in the patients carrying TSHR gene defects have not yet been clearly established. This study aimed to investigate the genetics of patients with CH to identify TSHR defects and to explore the specific extrathyroidal defects and other phenotypic features in these patients to establish a genotype-phenotype correlation.

METHODS: Consanguineous families with primary CH and a history of non-autoimmune acquired hypothyroidism were included in this study. The causative variants in the TSHR gene were identified using exome sequencing. Multiple in silico analysis tools were employed to interpret the variants.

RESULTS: Five TSHR variants including two novel variants were identified in patients with thyroid dysgenesis from five families. Some patients presented inter- and intra-familial variable expression and different ages of onset. The data suggest the possibility that the clinical phenotype of patients with CH caused by TSHR variants can be influenced by the coexistence of other gene defects.

CONCLUSIONS: This study investigated the variants of the TSHR gene contributing to CH for the first time in Iran. Our study on multiplex consanguineous families could help provide further evidence for the elucidation of the oligogenic inheritance in CH, possibly leading to variable expressivity in patients with CH. These data could have implications for genetic diagnosis and counseling to identify deleterious variants for possible diagnostics, clinical management, and preventive aims.

PMID:40391015 | PMC:PMC12086082 | DOI:10.3389/fendo.2025.1559281

Front Endocrinol (Lausanne). 2025 May 5;16:1555189. doi: 10.3389/fendo.2025.1555189. eCollection 2025.

ABSTRACT

BACKGROUND: Ovarian tissue cryopreservation and transplantation (OTCT) is an effective method for preserving fertility and endocrine function. This study aims to summarize the surgical techniques and perioperative experiences to provide clinical evidence for pediatric OTCT.

METHODS: This retrospective study reviewed the clinical data of 89 children who underwent umbilical single-incision laparoscopic oophorectomy at Children’s Hospital, Capital Institute of Pediatrics between September 2020 and December 2024. The types of primary diseases were summarized, differences in preoperative complete blood count results, surgery methods and intraoperative conditions were explored among different primary diseases. Different surgical methods were reviewed. The surgery steps and techniques were summarized. The trends in surgical volume over time and the surgical learning curve were analyzed. The factors affecting follicle density were also explored.

RESULTS: The primary diseases in this study included Turner syndrome, aplastic anemia, mucopolysaccharidosis in, chronic active Epstein-Barr virus (EBV) infection, hematological malignancies, solid tumors, platelet dysfuction, metachromatic leukodystrophy, hemophagocytic syndrome, myelodysplastic syndrome, beta-thalassemia, osteopetrosis, dermatomyositis, congenital dyserythropoietic anemia, metachromatic leukodystrophy, and primary immunodeficiency. Children received chemotherapy will experience a decrease in white blood cell (WBC) and neutrophil levels, necessitating granulocyte-stimulating therapy; children with aplastic anemia had a significant drop in hemoglobin level, thus requiring red blood cell transfusions; children with myelodysplastic syndrome and aplastic anemia showed a marked decrease in platelet levels, necessitating platelet transfusions. Children with Turner syndrome most commonly have the unclosed internal inguinal ring. The main steps of umbilical single-incision laparoscopic oophorectomy were incision, trocar placement, observation, suspension, dissection, removal, and incision closure. The number of umbilical single-incision laparoscopic oophorectomy had been increasing year by year. The learning curve analysis indicated that the first 35 cases were the learning and improvement phase. Follicular density was significantly correlated with age, primary disease and ovarian color.

CONCLUSION: Pediatric OTCT has broad applications and a promising future. Perioperative preparation and the surgical process are important. It is necessary to adjust the complete blood cell count to ensure that WBC greater than 4*10^9/L, neutrophils greater than 1*10^9/L, hemoglobin greater than 70 g/L, and platelet greater than 100*10^9/L before surgery. Given the small volume of children’s ovaries, it’s necessary to remove the entire ovary. Energy devices can be utilized, however, it’s essential to minimize mechanical, thermal damage, and warm ischemia time to the ovary, while also preserving surrounding tissues.

PMID:40391007 | PMC:PMC12086076 | DOI:10.3389/fendo.2025.1555189

Pediatr Int. 2025 Jan-Dec;67(1):e70077. doi: 10.1111/ped.70077.

ABSTRACT

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disorder that causes recurrent edema and abdominal/laryngeal attacks. However, the number of pediatric HAE cases is unknown. We aimed to assess the number of pediatric HAE and the actual status of pediatric HAE management in Japan.

METHODS: A mail questionnaire survey was conducted on 142 clinicians (representatives of institutes) with previous experience in HAE management. The survey items included the number of pediatric patients who were treated for HAE, history of attacks and its impact on quality of life, the presence of untested pediatric relatives of adult patients, and unmet needs.

RESULTS: In total, 69 representatives (49% of overall institutes) responded. Twenty-five (36% of respondents) had experience in pediatric HAE management. The number of cases managed by individual faculties ranged from 1 to 6, and most physicians (n = 16, 64% of faculties with patient(s)) reported the management of a single case only. There were 26 (8 male,16 female) patients with one or more attacks. Nineteen facilities (28% of respondents) reported one or more pediatric relative(s) of patients who were hesitant to screen. Further, physicians reported various unmet needs.

CONCLUSIONS: Pediatric HAE is managed in many facilities in a dispersed manner. In some cases, the pediatric relatives of patients diagnosed with HAE did not undergo screening. This study identified unmet needs and challenges that reflect the absence of specialized pediatric management. Hence, the standardization of pediatric HAE management is an urgent concern in Japan.

PMID:40390650 | DOI:10.1111/ped.70077

BMC Immunol. 2025 May 19;26(1):39. doi: 10.1186/s12865-025-00721-8.

ABSTRACT

BACKGROUND: Primary immunodeficiencies (PIDs) are a group of diseases that develop as a result of primary or congenital malfunction of the immune system and progress with chronic and/or recurrent bacterial, fungal, protozoal and/or viral infections. In this study, we aimed to examine the effects of the COVID-19 pandemic on depression, anxiety levels and psychological resilience in patients with PID and to compare them with those in controls.

METHODS: Seventy patients, aged 18-65 years, who were being followed up with a diagnosis of PID and 69 people as healthy control group, participated in our study. The participants were evaluated cross-sectionally once; sociodemographic data form, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Resilience Scale for Adults (RSA), and COVID-19 Evaluation form were administered to the participants.

RESULTS: HAM-A and HAM-D scores were significantly higher in PID patients compared to controls (HAM-D: 5.5 vs. 3.0, p < 0.001; HAM-A: 6.0 vs. 4.0, p = 0.008). RSA was significantly lower in the patient group (RSA total: 122.5 vs. 136.0, p < 0.001), and pandemic-related risk perception was higher (PRPS: 33.9 vs. 28.3, p < 0.001). Sleep, appetite, and attention-related disturbances were also more common in the patient group. Multivariate regression analyses revealed that PID diagnosis was an independent predictor of increased depression severity (HAM-D), lower psychological resilience (RSA), and greater pandemic-related risk perception. Female sex was independently associated with higher anxiety severity (HAM-A). A personal psychiatric history and greater number of comorbidities were also significant predictors of psychological vulnerability, particularly in relation to depression and anxiety.

CONCLUSION: Given the observed associations between PID and increased levels of depression, anxiety, and reduced psychological resilience during the pandemic, clinicians may consider heightened vigilance for psychological symptoms in this population during times of public health crisis.

PMID:40389841 | DOI:10.1186/s12865-025-00721-8

Biomed Rep. 2025 May 2;23(1):110. doi: 10.3892/br.2025.1988. eCollection 2025 Jul.

ABSTRACT

Tricho-hepato-enteric (THES) syndrome is a severe congenital diarrheal disorder. It is caused by homozygous or compound heterozygous mutations in the SKIC3 (THES1) or SKIC2 (THES2) gene. Primary manifestations include nine clinical signs: Ιntractable diarrhea, hair abnormalities, facial dysmorphism, IUGR, immunodeficiency, skin abnormalities, liver disease, congenital cardiac defects and platelet anomalies in the 96 cases reported to date. Α case of early, isolated severe fetal growth restriction with a non-placental etiology is presented, consistent with postnatal findings reported in the literature. Furthermore, this case introduces two novel prenatal ultrasound findings: Severe echogenic bowel, and dolichocephaly in contribution to the limited body of knowledge. Trio-whole exome sequencing (WES) analysis revealed that the embryo was compound heterozygous for two mutations in SKIC2, both of which were of parental origin. The report also discusses potential mechanisms underlying the observed ultrasound signs, highlighting that the expanded application of WES in prenatal settings will add more cases of sporadic disorder.

PMID:40386307 | PMC:PMC12082065 | DOI:10.3892/br.2025.1988

J Allergy Clin Immunol Pract. 2025 May 16:S2213-2198(25)00484-2. doi: 10.1016/j.jaip.2025.04.058. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic Granulomatous Disease (CGD) is a rare inborn error of immunity caused by mutations affecting individual components of the NADPH oxidase complex. Resultant defective neutrophil function leads to infectious and inflammatory complications, resulting in reduced quality of life and survival. Although haematopoietic stem cell transplant is a curative option, a significant proportion of patients are managed conservatively into adulthood. Skin manifestations are common in patients with uncorrected CGD but are poorly documented with no existing treatment guidelines.

OBJECTIVE: To document skin disease and response to treatment in adults with uncorrected CGD.

METHODS: We conducted a retrospective review in a large cohort of adults with CGD conservatively managed at a single centre in a joint Immunology/Dermatology clinic. Clinical, photographic, histological and treatment data were collected to assign distinct skin diagnoses and assess response to treatment.

RESULTS: 34/50 patients with X-linked or Autosomal Recessive CGD had skin involvement, typically with more than one skin diagnosis. Pustular eruptions, seborrheic dermatitis, rosacea and skin infections were most commonly seen. Mucocutaneous lupus, oro-facial granulomatosis and other pre-dominantly inflammatory diagnoses were seen in a smaller subset. Culture was positive in only 32.5% of the tests, even from pustular lesions. Typically, skin disease was difficult to treat with variable responses to treatment and frequent relapses.

CONCLUSIONS: A broad range of skin manifestations are seen in adults with CGD. It remains unclear to what extent CGD skin disease is contributed to by infection and/or an excessive inflammatory response, for example to skin microorganisms. Prolonged and intensive therapy is often required.

PMID:40383433 | DOI:10.1016/j.jaip.2025.04.058