Abstract
PurposeIndividuals with immunoglobulin G deficiency (IgGsd) often complain of fatigue. The correlation between systemic inflammation and fatigue is unknown. In this study perceived quality of life (QoL) and fatigue in individuals with IgGsd, on and off immunoglobulin replacement therapy (IgRT) were correlated to inflammatory markers in plasma to identify the subgroup that benefits from IgRT.MethodThirty-five IgGsd-patients were sampled on three occasions: at baseline, after being on IgRT for at least 18 months, and 18 months after discontinuation of IgRT. Short form 36, EQ-5D-5L visual analogue scale and fatigue impact scale questionnaires were used for evaluation of QoL and fatigue. Furthermore, a panel of 92 inflammatory markers were analysed in plasma. Thirty-two gender- and age-matched healthy individuals were included as controls and sampled on one occasion.ResultsQoL was lower and perceived fatigue higher in IgGsd compared to the controls. Severe fatigue and low QoL were associated with the need to restart IgRT (which is considered in IgGsd-individuals with a high burden of infections in Sweden). Twenty-five inflammatory factors were dysregulated in IgGsd and the plasma protein patterns were similar regardless of whether IgRT was ongoing or not. Enrichment analysis indicated IL-10 signalling as the most affected pathway. Severe fatigue was associated with decreased levels of the neurotrophic factors VEGFA and CSF-1.ConclusionFatigue is a major contributory factor to impaired health-related QoL in IgGsd and is related to the need for IgRT. Low-grade systemic inflammation is a potential driver of fatigue. In addition to the burden of infections, we suggest the degree of fatigue should be considered when the decision to introduce IgRT is made.
Highlights
Health-related quality of life (QoL) is a multidimensional concept that relate to an individual’s perceived physical and mental health
We found that low QoL and fatigue were common in IgG subclass deficiency (IgGsd) regardless of whether immunoglobulin replacement therapy (IgRT) was ongoing or not, and were most pronounced in those who needed to reintroduce IgRT due to the recurrence of frequent infections
Out of the 35 subjects that were recruited to the study, 18 (51%) needed to restart IgRT after the period of discontinuation, while 16 did not need the substitution and one had left the study
Summary
Health-related quality of life (QoL) is a multidimensional concept that relate to an individual’s perceived physical and mental health. Fatigue is a major cause of reduced QoL in many diseases, including cancer and chronic inflammatory disorders. In these conditions, fatigue has been reported to be associated with a poor prognosis and may even predict mortality [1,2,3,4]. Common variable immunodeficiency (CVID) is a PAD, characterised by reduced levels of total IgG and standard care includes lifelong immunoglobulin replacement therapy (IgRT) [5]. In Sweden, the need for IgRT in IgGsd is based on the frequency and severity of bacterial infections and/or the presence of lung damage. If bacterial respiratory tract infections reoccur, or if signs of reduced lung function develop, IgRT should be restarted [5]
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