Inborn errors of immunity underlying a susceptibility to pyogenic infections: from innate immune system deficiency to complex phenotypes

Conti, Francesca; Antonio, Miguel; Moratti, Mattia; Lodi, Lorenzo; Ricci, Silvia

doi:10.1016/j.cmi.2022.05.022

Cited by 5 publications

(2 citation statements)

References 72 publications

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“…Alternatively, compromised innate immunity resulting from underlying genetic conditions may be a factor. Studies 22,23 have shown that neutrophils play a key role in the innate immune system, and deficiencies in immune system components are often linked to increased susceptibility to severe infections. Inborn errors of immunity are also known to underlie infectious diseases.…”

Section: Discussionmentioning

confidence: 99%

Genetic Diseases and Invasive Infections in Infants 100 Days or Younger

Zhu

Bei

et al. 2023

Pediatric Infectious Disease Journal

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Background: Understanding the association of genetic diseases with invasive infections in neonates or infants is important, given the clinical and public health implications of genetic diseases. Methods: We conducted a retrospective case-control study over a 5-year period to investigate the association between genetic diseases and invasive infections in neonates or infants. The case group included 56 patients with laboratory-confirmed invasive infections and a genetic etiology identified by exome sequencing. Another 155 patients without a genetic etiology were selected as controls from the same pool of patients. Results: An overview of genetic diseases that predispose patients to develop invasive infections were outlined. We identified 7 independent predictors for genetic conditions, including prenatal findings [adjusted odds ratio (aOR), 38.44; 95% confidence interval (CI): 3.94–374.92], neonatal intensive care unit admission (aOR, 46.87; 95% CI: 6.30–348.93), invasive ventilation (aOR, 6.66; 95% CI: 3.07–14.46), bacterial infections (aOR, 0.21; 95% CI: 0.06–0.69), fever (aOR, 0.15; 95% CI: 0.08–0.30), anemia (aOR, 6.64; 95% CI: 3.02–14.59) and neutrophilia (aOR, 0.98; 95% CI: 0.96–0.99). The area under the curve for the predictive model was 0.921 (95% CI: 0.876–0.954). We also found that a genetic etiology [hazard ratio (HR), 7.25; 95% CI: 1.71–30.81], neurological manifestations (HR, 3.56; 95% CI: 1.29–9.88) and septic shock (HR, 13.83; 95% CI: 3.18–60.10) were associated with severe outcomes. Conclusions: Our study established predictive variables and risk factors for an underlying genetic etiology and its mortality in neonates or infants with invasive infections. These findings could lead to risk-directed screening and treatment strategies, which may improve patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Genetic Diseases and Invasive Infections in Infants 100 Days or Younger

Zhu

Bei

et al. 2023

Pediatric Infectious Disease Journal

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“…Furthermore, with advancements in sepsis research in recent years, it has been found that uncontrolled infection may lead to dysregulation of the host’s immune response. At the same time, excessive immune response results in the secretion of a multitude of cytokines, leading to organ dysfunction and, ultimately, host death ( 8 – 10 ). Therefore, effective prevention and treatment of serious infectious diseases has become critical.…”

Section: Introductionmentioning

confidence: 99%

The causal relationship between gut microbiota and nine infectious diseases: a two-sample Mendelian randomization analysis

Wang,

Yin,

Sun

et al. 2024

Front. Immunol.

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BackgroundEvidence from observational studies and clinical trials has associated gut microbiota with infectious diseases. However, the causal relationship between gut microbiota and infectious diseases remains unclear.MethodsWe identified gut microbiota based on phylum, class, order, family, and genus classifications, and obtained infectious disease datasets from the IEU OpenGWAS database. The two-sample Mendelian Randomization (MR) analysis was then performed to determine whether the gut microbiota were causally associated with different infectious diseases. In addition, we performed reverse MR analysis to test for causality.ResultsHerein, we characterized causal relationships between genetic predispositions in the gut microbiota and nine infectious diseases. Eight strong associations were found between genetic predisposition in the gut microbiota and infectious diseases. Specifically, the abundance of class Coriobacteriia, order Coriobacteriales, and family Coriobacteriaceae was found to be positively associated with the risk of lower respiratory tract infections (LRTIs). On the other hand, family Acidaminococcaceae, genus Clostridiumsensustricto1, and class Bacilli were positively associated with the risk of endocarditis, cellulitis, and osteomyelitis, respectively. We also discovered that the abundance of class Lentisphaeria and order Victivallales lowered the risk of sepsis.ConclusionThrough MR analysis, we found that gut microbiota were causally associated with infectious diseases. This finding offers new insights into the microbe-mediated infection mechanisms for further clinical research.

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