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.

Adverse COVID-19 outcomes in immune deficiencies: Inequality exists between subclasses.

BACKGROUND: Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS-CoV-2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID-19 outcomes. METHODS: We studied 34 IEI patients (19M/15F, 12 [min: 0.6-max: 43] years) from six centers. We diagnosed COVID-19 infection by finding a positive SARS-CoV-2 PCR test (n = 25) and/or a lung tomography scoring (CORADS) ≥4 (n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. RESULTS: Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID-related death (OR: 2.630, 95% CI; 1.198-5.776, p < .001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin-T, ferritin, and total-lung-score (p = .020, p = .003, p = .014, p = .013, p = .020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG (p = .012, p = .022, p = .011; respectively). CONCLUSION: Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID-19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS-Cov-2 therapy trials.

Evolution and long-term outcomes of combined immunodeficiency due to CARMIL2 deficiency.

BACKGROUND: Biallelic loss-of-function mutations in CARMIL2 cause combined immunodeficiency associated with dermatitis, inflammatory bowel disease (IBD), and EBV-related smooth muscle tumors. Clinical and immunological characterizations of the disease with long-term follow-up and treatment options have not been previously reported in large cohorts. We sought to determine the clinical and immunological features of CARMIL2 deficiency and long-term efficacy of treatment in controlling different disease manifestations. METHODS: The presenting phenotypes, long-term outcomes, and treatment responses were evaluated prospectively in 15 CARMIL2-deficient patients, including 13 novel cases. Lymphocyte subpopulations, protein expression, regulatory T (Treg), and circulating T follicular helper (cTFH ) cells were analyzed. Three-dimensional (3D) migration assay was performed to determine T-cell shape. RESULTS: Mean age at disease onset was 38 ± 23 months. Main clinical features were skin manifestations (n = 14, 93%), failure to thrive (n = 10, 67%), recurrent infections (n = 10, 67%), allergic symptoms (n = 8, 53%), chronic diarrhea (n = 4, 27%), and EBV-related leiomyoma (n = 2, 13%). Skin manifestations ranged from atopic and seborrheic dermatitis to psoriasiform rash. Patients had reduced proportions of memory CD4+ T cells, Treg, and cTFH cells. Memory B and NK cells were also decreased. CARMIL2-deficient T cells exhibited reduced T-cell proliferation and cytokine production following CD28 co-stimulation and normal morphology when migrating in a high-density 3D collagen gel matrix. IBD was the most severe clinical manifestation, leading to growth retardation, requiring multiple interventional treatments. All patients were alive with a median follow-up of 10.8 years (range: 3-17 years). CONCLUSION: This cohort provides clinical and immunological features and long-term follow-up of different manifestations of CARMIL2 deficiency.