Search

Pulmonary infection is the leading cause of infectious morbidity and mortality in children with immune defects. We provide a comprehensive review of lung infections in immunocompromised children, with a focus on imaging findings and imaging-based management. We include an overview of the immune defences of the respiratory tract, the aetiologies of immune defects in children, the features of specific infections and important differential diagnoses and describe diagnostic strategies using imaging and non-imaging-based techniques., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: There is a lack of data on post-HSCT non-osteopenic bone pathology specifically for children with inborn errors of immunity (IEI). We collected data on non-osteopenic bone pathology in children with IEI post-HSCT over two decades in a large tertiary pediatric immunology center., Methods: Descriptive study with data analysis of bone pathology in allo-HSCT for IEI was performed between 1/1/2000 to 31/12/2018 including patients alive at follow-up to July 2022. Records were analyzed for bone pathology and risk factors. Exclusion criteria included isolated reduced bone density, fractures, and skeletal anomalies due to underlying IEI and short stature without other bone pathology. Bone pathologies were divided into 5 categories: bone tumors; skeletal dysplasia; avascular necrosis; evolving bone deformities; slipped upper femoral epiphysis., Results: A total of 429 children received HSCT between 2000 and 2018; 340 are alive at last assessment. Non-osteopenic bone pathology was observed post-HSCT in 9.4% of patients (32/340, mean 7.8 years post-HSCT). Eleven patients (34%) had > 1 category of bone pathology. Seventeen patients (17/32; 53%) presented with bilateral bone pathology. The majority of patients received treosulfan-based conditioning (26/32; 81.2%). Totally, 65.6% (21/32) of patients had a history of prolonged steroid use (> 6 months). Pain was the presenting symptom in 66% of patients, and surgical intervention was required in 43.7%. The highest incidence of bone pathologies was seen in Wiskott-Aldrich syndrome (WAS) (n = 8/34; 23.5%) followed by hemophagocytic lymphohistiocytosis patients (n = 3/16; 18.8%)., Conclusion: Non-osteopenic bone pathology in long-term survivors of allo-HSCT for IEI is not rare. Most patients did not present with complaints until at least 5 years post-HSCT highlighting the need for ongoing bone health assessment for patients with IEI. Children presenting with stunted growth and bone pathology post-HSCT should undergo skeletal survey to rule out development of post-HSCT skeletal dysplasia. Increased rates and complexity of bone pathology were seen amongst patients with Wiskott-Aldrich syndrome., (© 2023. Crown.)

We investigated the anti-polysaccharide antibody responses in subjects with Down syndrome (DS) because DS subjects show decreased peripheral B-lymphocyte numbers in all age groups, and a clinical picture of recurrent respiratory tract infections and increased incidence of autoimmune diseases which is reminiscent of common variable immunodeficiency disorders (CVID)-like disease. We determined titers and opsonophagocytosis in response to conjugated and unconjugated pneumococcal serotypes in 18 DS subjects aged 6-24 years. The results show adequate serotype-specific antibody titers in response to all conjugated and almost all unconjugated serotypes used. Opsonophagocytosis activity as measured against pneumococcal serotypes 9N, 19F and 23F was also found to be intact. We conclude that DS subjects do not have a clear defect in their anti-polysaccharide antibody response., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We determined the response of 48 Down syndrome children to 2 doses of influenza A/H1N1 vaccination. Ninety-two percent of the children reached the previously defined protective level (hemagglutination-inhibition titer ≥1:40), but only 27% of the children reached the level of ≥1:110 which was recently described to predict the conventional 50% clinical protection rate in children. Further studies, and potentially adaptations of the schedule, are needed.

The immune system declines with aging, leading to an increased susceptibility to infections and higher incidence and progression of autoimmune phenomena and neoplasia. Down syndrome prematurely shows clinical manifestations that are normally seen with aging. This review provides a concise overview of abnormalities in the adaptive immune system of Down syndrome in comparison to normal and precocious (Progeria syndromes) aging. Clinical signs and immunological changes are reviewed. We challenge the hypothesis that the immunological abnormalities in Down syndrome should be interpreted as precocious immunosenescence.

Down syndrome children show a decreased avidity of the antibody response after tetanus toxoid booster vaccination at 9 years of age suggesting impaired memory B cell selection in the germinal center. Clinicians need to be aware of this ongoing subtle immunologic deficit in Down syndrome.

Because of their increased malignancies, autoimmune diseases, and infections, patients with Down syndrome (DS) show features of immunodeficiency. The DS thymus and T lymphocyte subsets have indeed proven to be different, and this has been interpreted as precocious aging. Our study on T lymphocyte subpopulations in DS shows that the normal expansion of naive helper (CD4CD45RA) and cytotoxic (CD8CD45RACD27) T lymphocytes is lacking in the first years of life; this is more logically explainable with an intrinsic T lymphocyte defect. Furthermore, memory cell numbers are not different from age-matched controls (AMC), which does not support the hypothesis of precocious aging. Although the absolute numbers of T lymphocyte subpopulations approach AMC levels toward adulthood, the persistent clinical problems suggest that these cells may not function optimally. However, the clinical picture does not fit severe T lymphocyte deficiency. The latter concept is also supported by our finding that cytomegalovirus (CMV)-seropositive DS children show similar numbers of terminally differentiated cytotoxic T lymphocytes when compared with healthy children, not increased numbers as are seen in immunocompromised hosts.

Down syndrome (DS) is known for increased incidence of respiratory infections and autoimmune diseases, indicating impaired immunity. Until now, attention has been mainly focused on T lymphocytes. Therefore, we determined B-lymphocyte subpopulations in 95 children with DS compared with 33 age-matched control (AMC) children. DS serum immunoglobulin levels were compared with 962 non-DS children with recurrent infections. The results were combined with clinical data. Transitional and naive B lymphocytes are profoundly decreased in the children with DS. This could be caused by an intrinsic B-lymphocyte defect resulting in (partial) failure of B-lymphocyte generation, decreased antigen-induced proliferation and/or increased apoptosis, or by decreased proliferation due to deficient T-lymphocyte help, or a combination of these. The decreased CD27, CD21, and CD23 cells are reminiscent of common variable immunodeficiency and suggestive of disturbed peripheral B-lymphocyte maturation. Immunoglobulin levels in DS are abnormal-as has been described before-and different from non-DS children with recurrent infections. We conclude that the humoral immune system is abnormal in DS, but could not find a relation between B-lymphocyte subsets, immunoglobulins and clinical features of the children with DS in our cohort, nor could we answer the question whether DS lymphocytes are truly intrinsically deficient, or could all findings be explained by deficient T-lymphocyte help.

Down syndrome (DS) is the most frequent cause of mental retardation in man. Immunological changes in DS have been observed since the 1970s. The neurological system appears to be ageing precociously, with early occurrence of Alzheimer disease; until now, the observed immunological differences have been interpreted in the same context. Looking back at past and present results of immunological studies in DS children in relation to the clinical consequences they suffer, we conclude that it is more likely that the DS immune system is intrinsically deficient from the very beginning.