Pituicytoma is a tumor extremely rare in childhood, with only 4 cases reported in literature. It is thought to arise from the specialized glial elements called "pituicytes." The association of ...pituicytoma and Cushing's disease (CD) has been described only once so far, in an adult patient. A 7-year-old girl was referred for clinical signs of hypercortisolism, and a diagnosis of CD was made. MRI revealed 2 pathologic areas in the pituitary gland. The patient underwent surgery, with microscopic transsphenoidal approach, and a well-circumscribed area of pathologic tissue was identified and removed. Surprisingly, histologic and immunohistochemical study provided unequivocal evidence of pituicytoma. No pituitary adenoma could be identified. For persistent hypercortisolism, the patient necessitated transsphenoidal endoscopic reintervention and 2 other lesions were removed. By immunohistological examination, these lesions were confirmed to be corticotropin-secreting adenoma. Unfortunately, there was no postoperative decrease in corticotropin and cortisol levels, and the patient underwent bilateral laparoscopic adrenalectomy. Considering that we report a second case of association of pituicytoma and corticotropin-secreting adenoma, that CD is infrequent, and pituicytoma is extremely rare in childhood, the coexistence of these 2 tumors should not be considered a mere coincidence. To date, there is no conclusive evidence about the origin of these different subtypes of pituitary tumors. This case supports the hypothesis that these tumors share a common progenitor cell, which could be the folliculostellate cell.
As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. ...We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.
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•Antibody neutralization is inversely associated with SARS-CoV-2 in nasopharyngeal swabs•Antigen-specific B cells positively associate with anti-SARS-CoV-2 humoral immunity•SARS-CoV-2 neutralizing antibodies are present in patients with higher specific T cells•Antigen-specific B and T cells are features of SARS-CoV-2 immunity in children
Cotugno et al. show that neutralizing antibodies affect SARS-CoV-2 viral load in infected children. Antigen-specific B and T cells are positively associated with virus neutralization. This information provides a basis for defining SARS-CoV-2 adaptive responses in children.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 ...families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.
Abstract
Background
Immunization of vulnerable populations with distinct immunity often results in suboptimal immunogenicity, durability, and efficacy.
Methods
Safety and immunogenicity profiles of ...BNT162b2 messenger RNA coronavirus disease 2019 (COVID-19) vaccine, among people living with human immunodeficiency virus (HIV), were evaluated in 28 perinatally HIV-infected patients under antiretroviral therapy (ART) and 65 healthy controls (HCs) with no previous history of COVID-19. Thus, we measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific humoral and CD4+ T cell responses. Samples were collected before vaccination (baseline, day D 0), at the second dose (D21), and at 4 weeks (D28) and 6 months (D180) after D0. Proteomic profiles at D0 and D28 were assessed with a multiplexed proximity extension assay (Olink) on plasma samples.
Results
All HIV-infected patients mounted similar anti–SARS-CoV-2 humoral responses to those of HCs, albeit with lower titers of anti-trimeric S at D28 (P = .01). Only peripheral blood mononuclear cells of HIV-infected patients demonstrated at D28 an impaired ability to expand their specific (CD40L+) CD4+ T-cell populations. Similar humoral titers were maintained between the 2 groups at 6-months follow-up. We additionally correlated baseline protein levels to either humoral or cellular responses, identifying clusters of molecules involved in immune response regulation with inverse profiles between the 2 study groups.
Conclusions
Responses of ART-treated HIV-infected patients, compared to those of HCs, were characterized by distinct features especially within the proteomic compartment, supporting their eligibility to an additional dose, similarly to the HC schedule.
In comparison to healthy individuals, perinatally HIV-infected patients with normal CD4 T-cell counts at the time of enrollment and with distinct baseline proteomic profiles mount and maintain specific immune responses upon BNT162b2 vaccination.
Despite the multiple benefits of vaccination, cardiac adverse Events Following COVID-19 Immunization (c-AEFI) have been reported. These events as well as the severe cardiac involvement reported in ...Multisystem inflammatory syndrome in children (MIS-C) appear more frequent in young adult males. Herein, we firstly report on the inflammatory profiles of patients experiencing c-AEFI in comparison with age, pubertal age and gender matched MIS-C with cardiac involvement. Proteins related to systemic inflammation were found higher in MIS-C compared to c-AEFI, whereas a higher level in proteins related to myocardial injury was found in c-AEFI. In addition, higher levels of DHEAS, DHEA, and cortisone were found in c-AEFI which persisted at follow-up. No anti-heart muscle and anti-endothelial cell antibodies have been detected. Overall current comparative data showed a distinct inflammatory and androgens profile in c-AEFI patients which results to be well restricted on heart and to persist months after the acute event.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Kawasaki disease (KD) is an acute vasculitis occurring in children <5yo that can result in coronary artery lesions. Our study aims to define novel pathogenetic and diagnostic signatures ...through flow cytometry and gene expression of T cell subsets. Peripheral Blood Mononuclear Cells of twenty-four KD patients at diagnosis (KD), twelve febrile patients (FC) and eighteen age-matched healthy controls (HC) were collected. Frequency of T regulatory cells (Treg), peripheral T follicular helper cells (pTfh) and maturational T cell subsets (Naïve, Central Memory, CM; Effector Memory, EM; terminally differentiated memory, TEMRA) were assessed by FACS (CytoFLEX-Beckman Coulter). Transcriptional levels of 96-genes in sort-purified CM, Treg and EM have been analysed by Fluidgm (Biomark). We found that KD have lower frequency of CM and EM compared to HC (p=0.003 and p=0.005), lower frequency of pTfh cells compared to HC (p=0,008), and in line with previous literature, lower Treg compared to HC (p=0.07). Instead, FC have a higher frequency of EM (p= 0.002; p=0.001) and TEMRA (p=0.004; p=0.006) and lower Naive (p=0.005; p=0.003) compared with both HC and KD. At transcriptional level, a distinct signature was found in EM of FC, with 26 and 16 differentially expressed genes (DEGs) compared to KD and HC. These preliminary data suggest that KD present a distinct phenotypic and transcriptional T cell signature, suggesting additional diagnostic and pathogenic insights able to distinguish KD from FC. Future studies with a similar multi OMIC approach could help identifying prognostic signature in KD.
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