Blog

Ital J Pediatr. 2023 Feb 10;49(1):19. doi: 10.1186/s13052-022-01392-6.

ABSTRACT

Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants. The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents’ education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis.

PMID:36765418 | DOI:10.1186/s13052-022-01392-6

Gac Med Mex. 2023 Jan 20;158(Suplement 2):1-116. doi: 10.24875/GMM.M22000690.

ABSTRACT

With the advancement of knowledge in relation to the physiopathogenesis of atopic dermatitis (AD), several new therapeutic forms have been developed. There are also new guidelines for self-care. On the other hand, there is still an underdiagnosis of AD in Mexico. Thus, the need was seen to develop a national guide, with a broad base among the different medical groups that care for patients with AD. The Atopic Dermatitis Guidelines for Mexico (GUIDAMEX) was developed with the ADAPTE methodology, with the endorsement and participation of ten national medical societies, from physicians in Primary Healthcare to allergists and dermatologists. Throughout the manuscript, key clinical questions are answered that lead to recommendations and suggestions for the diagnosis of AD (including differential diagnosis with immunodeficiency syndromes), the recognition of comorbidities and complications, non-pharmacological treatment including therapeutic education, treatment of flares and maintenance therapy. The latter encompasses general measures to avoid triggering factors, first-line treatment focussed on repair of the skin barrier, second-line treatment (topical proactive therapy), and third-line phototherapy or systemic treatment, including dupilumab and JAK inhibitors.

PMID:36763412 | DOI:10.24875/GMM.M22000690

J Allergy Clin Immunol. 2023 Feb 7:S0091-6749(23)00147-1. doi: 10.1016/j.jaci.2023.01.022. Online ahead of print.

ABSTRACT

BACKGROUND: Lymphopenia, particularly restricted to the T-cell compartment, has been described as one of the major clinical hallmarks in COVID-19 patients and proposed as a disease severity indicator. Although several mechanisms fostering COVID-19-related lymphopenia have been described, including cell apoptosis and tissue homing, the underlying causes of the decline in T-cell count and function are still not completely understood.

OBJECTIVE: Given that viral infections can directly target thymic microenvironment and impair the process of T-cell generation, we sought to investigate the impact of SARS-CoV-2 on thymic function.

METHODS: We performed molecular quantification of T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) to assess, respectively, T- and B-cell neogenesis in SARS-CoV-2-infected patients. We developed in vitro culture system of primary human thymic epithelial cells (TECs) to mechanistically investigate the impact of SARS-CoV-2 on TEC function.

RESULTS: We showed that COVID-19 patients had reduced thymic function, which was inversely associated with the severity of the disease. We found that angiotensin-converting enzyme 2 (ACE2), through which SARS-CoV-2 enters the host cells, was expressed by thymic epithelium, and in particular by medullary TECs. We also demonstrated that SARS-CoV-2 can target TECs and downregulate critical genes and pathways associated with epithelial cell adhesion and survival.

CONCLUSIONS: Our data demonstrate that the human thymus is a target of SARS-CoV-2 and thymic function is altered upon infection. These findings expand our current knowledge of the effects of SARS-CoV-2 infection on T-cell homeostasis and suggest that monitoring thymic activity may represent a useful marker to predict disease severity and progression.

PMID:36758836 | DOI:10.1016/j.jaci.2023.01.022

J Clin Immunol. 2023 Feb 9. doi: 10.1007/s10875-023-01439-1. Online ahead of print.

NO ABSTRACT

PMID:36757554 | DOI:10.1007/s10875-023-01439-1

Front Immunol. 2023 Jan 23;14:1080129. doi: 10.3389/fimmu.2023.1080129. eCollection 2023.

ABSTRACT

Dendritic cells (DCs) are crucial cells for initiating and maintaining immune response. They play critical role in homeostasis, inflammation, and autoimmunity. A number of molecules regulate their functions including synapse formation, migration, immunity, and induction of tolerance. A number of IEI are characterized by mutations in genes encoding several of these molecules resulting in immunodeficiency, inflammation, and autoimmunity in IEI. Currently, there are 465 Inborn errors of immunity (IEI) that have been grouped in 10 different categories. However, comprehensive studies of DCs have been reported in only few IEI. Here we have reviewed biology of DCs in IEI classified according to recently published IUIS classification. We have reviewed DCs in selected IEI in each group category and discussed in depth changes in DCs where significant data are available regarding role of DCs in clinical and immunological manifestations. These include severe immunodeficiency diseases, antibody deficiencies, combined immunodeficiency with associated and syndromic features, especially disorders of synapse formation, and disorders of immune regulation.

PMID:36756122 | PMC:PMC9899832 | DOI:10.3389/fimmu.2023.1080129

Medicine (Baltimore). 2023 Feb 3;102(5):e32816. doi: 10.1097/MD.0000000000032816.

ABSTRACT

RATIONALE: Activated phosphoinositide 3-kinase δ syndrome (APDS), a recently described primary immunodeficiency,is caused by autosomal dominant mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta(PIK3CD) gene encoding the p110δ catalytic subunit of PI3Kδ (APDS1) or the PIK3R1 gene that encodes the p85α regulatory subunit of PI3Kδ (APDS2). Gain-of-function mutation of PIK3CD in APDS1 leads to p110δ hyperactivity, with the result of the hyperphosphorylation of downstream mediators of Akt and mammalian target of rapamycin that cause a series of clinical symptoms. Few cases with APDS were reported in Asia.

PATIENT CONCERNS: We report a 6-year-old patient with a recurrent respiratory infection, cryptosporidium enteritis, lymphoproliferation, high serum immunoglobulin-M level, anemia, and inverted CD4+/CD8+ ratio. The whole exome sequencing confirmed a heterozygous missense mutation c.3061G>A（p.E1021K）in patient and her mother. Her mutant gene is inherited from her mother, but her mother has not any clinical symptoms.

DIAGNOSES: Activated phosphoinositide 3-kinase δ syndrome.

INTERVENTIONS: The patient was received immunoglobulin (Ig) replacement therapy, antibiotics, and rapamycin treatment. Through effectively controlling infection and optimal timing of transplantation by adjusting the conditioning regimen, haploidentical Hematopoietic Stem Cell Transplantation(haplo-HSCT) from her brother was successfully performed.

OUTCOMES: The patient is in good condiion with a good quality of life after 20 months of follow-up.

LESSONS: We reported a rare APDS1 case with PIK3CDE1021K gene mutation, Successfully treated with haplo-HSCT. This case provided a reference for treating APDS with haplo-HSCT.

PMID:36749229 | DOI:10.1097/MD.0000000000032816

Front Immunol. 2023 Jan 20;14:1084630. doi: 10.3389/fimmu.2023.1084630. eCollection 2023.

ABSTRACT

PURPOSE: To describe SARS-CoV-2 infection outcome in unvaccinated children and young adults with inborn errors of immunity (IEI) and to compare their specific acute and long-term immune responses with a sex-, age-, and severity-matched healthy population (HC).

METHODS: Unvaccinated IEI patients up to 22 years old infected with SARS-CoV-2 were recruited along with a cohort of HC. SARS-CoV-2 serology and ELISpot were performed in the acute phase of infection (up to 6 weeks) and at 3, 6, 9, and 12 months.

RESULTS: Twenty-five IEI patients (median age 14.3 years, min.-max. range 4.5-22.8; 15/25 males; syndromic combined immunodeficiencies: 48.0%, antibody deficiencies: 16.0%) and 17 HC (median age 15.3 years, min.-max. range 5.4-20.0; 6/17 males, 35.3%) were included. Pneumonia occurred in 4/25 IEI patients. In the acute phase SARS-CoV-2 specific immunoglobulins were positive in all HC but in only half of IEI in whom it could be measured (n=17/25): IgG⁺ 58.8% (10/17) (p=0.009); IgM⁺ 41.2% (7/17)(p<0.001); IgA⁺ 52.9% (9/17)(p=0.003). Quantitative response (index) was also lower compared with HC: IgG IEI (3.1 ± 4.4) vs. HC (3.5 ± 1.5)(p=0.06); IgM IEI (1.9 ± 2.4) vs. HC (3.9 ± 2.4)(p=0.007); IgA IEI (3.3 ± 4.7) vs. HC (4.6 ± 2.5)(p=0.04). ELISpots positivity was qualitatively lower in IEI vs. HC (S-ELISpot IEI: 3/11, 27.3% vs. HC: 10/11, 90.9%; p=0.008; N-ELISpot IEI: 3/9, 33.3% vs. HC: 11/11, 100%; p=0.002) and also quantitatively lower (S-ELISpot IEI: mean index 3.2 ± 5.0 vs. HC 21.2 ± 17.0; p=0.001; N-ELISpot IEI: mean index 9.3 ± 16.6 vs. HC: 39.1 ± 23.7; p=0.004). As for long term response, SARS-CoV-2-IgM⁺ at 6 months was qualitatively lower in IEI(3/8, 37.5% vs. 9/10 HC: 90.0%; p=0.043), and quantitatively lower in all serologies IgG, M, and A (IEI n=9, 1.1 ± 0.9 vs. HC n=10, 2.1 ± 0.9, p=0.03; IEI n=9, 1.3 ± 1.5 vs. HC n=10, 2.9 ± 2.8, p=0.02; and IEI n=9, 0.6 ± 0.5 vs. HC n=10, 1.7 ± 0.8, p=0.002 -respectively) but there were no differences at remaining time points.

CONCLUSIONS: Our IEI pediatric cohort had a higher COVID-19 pneumonia rate than the general age-range population, with lower humoral and cellular responses in the acute phase (even lower compared to the reported IEI serological response after SARS-CoV-2 vaccination), and weaker humoral responses at 6 months after infection compared with HC.

PMID:36742319 | PMC:PMC9896004 | DOI:10.3389/fimmu.2023.1084630

Zhonghua Jie He He Hu Xi Za Zhi. 2023 Feb 12;46(2):158-163. doi: 10.3760/cma.j.cn112147-20220712-00594.

ABSTRACT

A 28-year-old male with a history of leukopenia was admitted with complaints of fever, cough, and dyspnea for 3 months. Initial work-up identified reduced circulating levels of granulocytes, monocytes, lymphocytes, and NK cells. Computed tomography revealed bilateral reticulonodular opacities and mediastinal lymph node enlargement. Peripheral blood culture and mediastinal lymph node aspiration yielded Mycobacterium avium. Genetic testing revealed a heterozygous germline GATA2 mutation (c.1187G>A, R396Q). Despite standard anti-mycobacterial therapy, the patient’s dyspnea worsened and subsequent imaging studies revealed diffuse ground-glass opacification. A transbronchial lung biopsy confirmed the development of pulmonary alveolar proteinosis. Bone marrow transplantation had not been performed due to the unavailability of suitable donors. The disease progressed after whole lung lavage, and the patient died at the age of 31 years from respiratory failure. The current case report emphasized the importance of raising awareness about the rare GATA2 deficiency, which is characterized by hematologic abnormalities, primary immunodeficiency, and pulmonary alveolar proteinosis.

PMID:36740376 | DOI:10.3760/cma.j.cn112147-20220712-00594

Indian J Tuberc. 2023 Jan;70(1):129-133. doi: 10.1016/j.ijtb.2022.04.008. Epub 2022 Apr 30.

ABSTRACT

Mendelian Susceptibility to Mycobacterial Disease describes a spectrum of inherited defects, of which complete deficiency of the interleukin-12 receptor β subunit 1 (IL-12Rβ1) is the most common cause. This condition results in a predisposition to severe disease caused by mycobacteria. We report a case of disseminated multidrug-resistant tuberculosis with extensive central nervous system affection with SARS-CoV-2 co-infection, in a 4-year-old child with IL-12Rβ1 complete deficiency.

PMID:36740310 | DOI:10.1016/j.ijtb.2022.04.008

Clin Exp Med. 2023 Feb 3. doi: 10.1007/s10238-023-01006-3. Online ahead of print.

ABSTRACT

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. CVID embraces a plethora of heterogeneous manifestations linked to complex immune dysregulation. While CVID is thought to be due to genetic defects, the exact cause of this immune disorder is unknown in the large majority of cases. Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. Here we discuss the potential of treating CVID patients by developing a gut microbiome-based personalized approach, including diet, prebiotics, probiotics, postbiotics and fecal microbiota transplantation. We also highlight the need for a better understanding of microbiota-host interactions in CVID patients to prime the development of improved preventive strategies and specific therapeutic targets.

PMID:36737487 | DOI:10.1007/s10238-023-01006-3