Diverse Clinical and Immunological Profiles in Patients with IPEX Syndrome: a Multicenter Analysis from Turkey.

PURPOSE: Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic FOXP3 variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease. METHODS: Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cTFH) cells, and T-cell proliferation were analyzed. RESULTS: Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the TH2-like skewing accompanied by reduced TH17-like responses was observed in cTFH and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs. CONCLUSIONS: The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome.

Long-term immunological changes after corrective cardiac surgery.

Infants with congenital heart disease (CHD) often undergo thymectomy during corrective cardiac surgery (CCS). The long-term immunological effects remain controversial, with concerns regarding increased susceptibility to infections, allergies, autoimmunity due to compromised immune tolerance mechanisms. This study aims to elucidate the long-term immunological effects of early thymectomy. We enrolled 22 patients who underwent thymectomy in infancy and were followed up in the Pediatric Allergy and Immunology Clinic at Marmara University. We performed demographic characteristics and detailed immunological evaluation, including immunoglobulins, vaccine responses, lymphocyte subset analyses, upregulation, proliferation of T cells and T-cell receptor excision circles (TRECs). Sixteen patients had a history of infection, including six serious infections, all in the first year. Lymphopenia was observed in 27% of patients, with a significant decrease in naive CD4+ and recent thymic emigrant T cells counts and an increase in the proportion of memory T-cells, indicating premature immune senescence. Low levels of IgG, IgA and IgM were found in 36%, 40% and 22% of patients respectively. Vaccine responses were positive in 90% of patients. TREC levels were low in all 10 patients analysed. Seven of nine patients had normal proliferation. Twenty-two percent of patients had allergic disease, and autoimmunity was not observed. Early thymectomy leads to permanent immunological changes that are indicative of early immunosenescence. It is recommended to preserve thymic tissue during surgery and requires long-term follow-up in terms of findings such as allergy and autoimmunity as well as infections due to impaired immune tolerance mechanisms.

Laboratory and clinical features of tumor lysis syndrome in children with non-Hodgkin lymphoma and evaluation of long-term renal functions in survivors.

OBJECTIVE: The purpose of our study is to investigate the laboratory and clinical features of tumor lysis syndrome (TLS) and acute kidney injury (AKI) in childhood non-Hodgkin lymphomas (NHL) and to reveal their impact on long term kidney function in survivors. METHODS: Our single-center retrospective study included 107 patients (0-18 years old) with NHL who were admitted and treated at our hospital between 1998 and 2020. The relationship between TLS and age, gender, histopathological subgroup, tumor stage, lactate dehydrogenase (LDH) level at presentation, bone marrow and kidney involvement were assessed. The long-term renal functions of the patients were investigated. RESULTS: 80.3% of the patients were male with a median age of 9.8 years. The most common detected histopathological subgroup was Burkitt lymphoma. Hyperhydration with or without alkalinisation, and allopurinol were used in first-line treatment and prophylaxis of TLS. Laboratory TLS and clinical TLS was observed in 30.8% and 12.1% of patients, respectively. A significant correlation was found between young age, advanced stage, high LDH level at presentation, and TLS. AKI was observed in 12.1% of the patients. When the glomerular filtration rate values of the patients at the first and last admissions were compared after an average of 6.9 years, a mean decrease of 10 mL/min/1.73 m2 was found. It was not, however, found to be statistically significant. CONCLUSION: Lower age, advanced stage, and high LDH level at presentation were found to be risk factors for TLS in our study. Long-term renal function loss was not observed in the survivors who received early and careful prophylaxis/treatment for TLS. The survivors are still being followed up.

Coats plus syndrome: a rare cause of severe gastrointestinal tract bleeding in children - a case report.

BACKGROUND: Coats plus syndrome, cerebroretinal microangiopathy with calcifications and cysts, is a rare disease with autosomal recessive pattern occurring due to a mutation in CTC1, encoding conserved telomere maintenance component 1, gene. Besides retinal involvement, abnormalities in brain and osteopenia, serious life-threatening bleeding in gastrointestinal tract and portal hypertension can be observed. CASE PRESENTATION: A 6-year-old girl with Coats plus syndrome presented to the pediatric emergency department with vomiting blood and blood in stool. An upper and lower gastrointestinal endoscopy revealed esophageal varices and vascular telangiectasia in the pyloric antrum, duodenum, and colon. She received palliative care and the bleeding was stopped after receiving intravenous octreotide. She then was followed in the pediatric gastroenterology, neurology, and ophthalmology clinics. She was later hospitalized and admitted to the intensive care unit as she continued to have intermittent gastrointestinal system bleeding. She eventually died due to severe gastrointestinal system bleeding. CONCLUSIONS: Coats plus syndrome can lead to life-threatening gastrointestinal bleeding and portal hypertension. As Coats plus syndrome is quite rare, there is little published data on this syndrome. This report presents a case of Coats plus syndrome as a rare cause of gastrointestinal bleeding and portal hypertension.