Body Weight and Infectious Outcomes in Patients with Primary Immunodeficiency Diseases: Outcomes from within the US Immunodeficiency Network (USIDNET).

Ruffner, Melanie A.; Sullivan, Kathleen E.

doi:10.1016/j.jaci.2015.12.718

Cited by 4 publications

(3 citation statements)

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“…The analysis carried out by the authors of this study also showed that BMI weakly but statistically significantly (p < 0.05) correlated with the age of the first symptoms. Certainly, this small difference in the results is due to differences between the groups discussed above (Table S3 in Supplementary Materials) [17].…”

Section: Discussionmentioning

confidence: 94%

Points to Consider in Health Assessment of Adult Patients with Primary Antibody Deficiencies

Napiórkowska-Baran,

Ziętkiewicz,

Więsik-Szewczyk

et al. 2023

JCM

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An improved recognition of inborn errors of immunity (IEI) is associated with an increase in life expectancy and a higher incidence of complications and related conditions. The aim of the study was to analyze factors enabling the primary prevention: BMI, smoking and selected laboratory tests (morphology with smear, creatinine, eGFR, total protein, albumin, ferritin, folic acid, vitamin B12, vitamin D3) included in the protocols of standard of care for adult patients with primary antibody deficiencies (PADs). The study included 94 participants ≥ 18 years old, diagnosed with PADs. Overweight was found in 17%, obesity in 14% and underweight in 15% of patients; 11.5% of patients smoked. Leukopenia was diagnosed in 16%, neutropenia in 8.5%, lymphopenia in 22.5% and thrombocytopenia in 14% of patients. A decreased concentration of hemoglobin was found in 32%, total protein in 19%, albumin in 17%, vitamin D3 in 52%, vitamin B12 in 6.5%, folic acid in 34% and ferritin in 26% of patients. Creatinine concentrations were elevated in 16% of patients, while in 20%, eGFR was reduced. Only a holistic assessment of comorbidities and complications of deficiency, as well as regular follow-up and lifestyle changes, can yield the best results in the long-term care of patients.

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Section: Discussionmentioning

confidence: 94%

Points to Consider in Health Assessment of Adult Patients with Primary Antibody Deficiencies

Napiórkowska-Baran,

Ziętkiewicz,

Więsik-Szewczyk

et al. 2023

JCM

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“…Data examining the impact of obesity on primary immunodeficiency outcomes are scarce, and very few studies have evaluated drug concentrations prospectively. One study reported an increase in sepsis (12% versus 6%; p = 0.05) in patients with obesity and common variable immune deficiency versus normal-weight patients [ 28 ]. Other studies suggest no difference in IgG exposure between obese and non-obese individuals [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Body Composition and Serum Immunoglobulin Concentrations after Administration of Intravenous Immune Globulin–Preclinical and Clinical Evidence

et al. 2023

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The purpose of this study was to investigate the effect of obesity on immunoglobulin G (IgG) pharmacokinetics in a rat model of obesity, and to collect clinical evidence for an association between the body composition and intravenous immune globulin (IVIG) pharmacokinetic parameters in humans. In a preclinical study, pharmacokinetics of human IgG was evaluated after intravenous (IV) and subcutaneous (SC) delivery to obese and lean rats (n = 6 in each group). Serial serum samples were analyzed using an ELISA. The animal body composition was assessed using computer tomography. Patients with primary immunodeficiency currently managed with IVIG, and at a steady state, were enrolled in the clinical study (n = 8). Serum immune globulin (Ig) concentrations were measured at baseline and immediately after the administration of two consecutive treatments, with an additional measurement at two weeks after the first administration. In addition to the patient demographic and clinical characteristics, body composition was measured using bioelectrical impedance analysis. The pharmacokinetics of human IgG was significantly different between the obese and lean rats after both the IV and SC administration of 0.5 g/kg. Furthermore, a significant difference in endogenous rat IgG was observed between the two strains. In the human study, total serum IgG and subtype (IgG1, IgG2, IgG3, IgG4) half-life negatively correlated with the body mass index and fat mass. The mean change in the total serum IgG concentration was significantly correlated to body mass index and fat mass. The results of the studies corroborated one another. In the animal study, most pharmacokinetic parameters of human IgG following IV and SC administration were significantly affected by obesity and changes in the body composition. In the clinical study, the mean serum IgG change after the IVIG administration strongly correlated to the BMI and body fat mass. Future studies are needed to establish the outcomes achieved with more frequent dosing in obese individuals with primary immunodeficiency.

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“…Patients with PIDs have been observed to have growth defects, mainly in children [63, 64]. Risk for infection have also been linked to factors including body mass index and adipose deposition due to the immunomodulatory effects of the tissue, but less is understood of the metabolic dynamics in patients with PIDs [65, 66]. An intimate association between primary immunodeficiencies and primary metabolic diseases is supported by the observation that mitochondrial disease patients manifest significant immunological defects, [67, 68], and some studies have linked inborn errors of metabolism (IEM) as mimicking or exacerbating immune defects [69].…”

Section: Discussionmentioning

confidence: 99%

NF-κB-Inducing Kinase Maintains Mitochondrial Efficiency and Systemic Metabolic Homeostasis

Pflug

Lee

Sitcheran

2021

Preprint

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Obesity is a predominant risk factor for metabolic syndrome, which refers to a cluster of disorders that include diabetes, cardiovascular disease and fatty liver disease. Obesity and overnutrition are associated with aberrant immune and inflammatory responses resulting in increased local fat deposition, insulin resistance and systemic metabolic dysregulation. Here we show NF-κB-inducing kinase (NIK), a critical regulator of immunity and inflammation has local and systemic effects on metabolic processes. We demonstrate that NIK has NF-κB-independent and -dependent roles on adipose development and function. Independently of noncanonical NF-κB, NIK deficiency regulates mitochondrial spare respiratory capacity (SRC) and proton leak but establishes higher basal oxygen consumption and glycolytic capacity in preadipocytes and ex vivo adipose tissue. In addition, we demonstrate NIK promotes adipogenesis through its role in activation of the noncanonical NF-κB pathway. Strikingly, when challenged with a high fat diet, NIK deficient mice are protected against diet-induced obesity and insulin insensitivity. Overall, mice lacking NIK exhibit decreased overall fat mass and increased energy expenditure. Our results establish that, through its influences on adipose development, metabolic homeostasis and rewiring, NIK is a driver of pathologies associated with metabolic dysfunction.

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Body Weight and Infectious Outcomes in Patients with Primary Immunodeficiency Diseases: Outcomes from within the US Immunodeficiency Network (USIDNET).

Cited by 4 publications

References 0 publications

Points to Consider in Health Assessment of Adult Patients with Primary Antibody Deficiencies

Points to Consider in Health Assessment of Adult Patients with Primary Antibody Deficiencies

Relationship between Body Composition and Serum Immunoglobulin Concentrations after Administration of Intravenous Immune Globulin–Preclinical and Clinical Evidence

NF-κB-Inducing Kinase Maintains Mitochondrial Efficiency and Systemic Metabolic Homeostasis

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