Fatigue Is Common in Immunoglobulin G Subclass Deficiency and Correlates With Inflammatory Response and Need for Immunoglobulin Replacement Therapy

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.

Clinical and immunological characterization of IgG subclass deficiency reveals that low levels of pneumococcal antibodies associate with need of immunoglobulin replacement therapy

“…The level of fatigue has previously been described in the present cohort [14]. Fatigue was evaluated by fatigue impact scale (FIS) [15], and FIS-score 60 or above was considered consistent with severe fatigue and was previously found to be associated with the need of IgRT [14]. Handling of blood samples and routine laboratory measurements Blood samples were drawn in vacutainers, and routine laboratory analyses and immune phenotyping were performed according to national treatment guidelines for IgGsd including levels of IgG, IgA, IgM, and IgG subclasses IgG1, IgG2 and IgG3 on fresh samples [11].…”

“…4C). We have recently shown that fatigue is more common in IgGsd patients with need of IgRT in the present cohort of patients [14]. This led us to include severe fatigue among factors that may predispose for the need to reintroduce IgRT.…”

“…1B). The group of IgGsd patients was heterogeneous, with diverse types of comorbidities (Table 1), and has previously been described in detail [14]. IgG3 de ciency was present in ten of the 16 patients with normal levels of total IgG.…”

Ginsenoside Rg1 can reverse fatigue behavior in CFS rats by regulating EGFR and affecting Taurine and Mannose 6-phosphate metabolism

“…VEGFA is a key regulator of vascular growth. Angiogenesis in skeletal muscle can maintain oxygen and nutrient supply and clear metabolic byproducts that may lead to fatigue ( Mohamad Shalan et al, 2016 ), which is associated with decreased levels of VEGFA ( Wågström et al, 2021 ). A study on metabolic gene polymorphisms conducted progressive fatigue tests on athletes and identified VEGFA rs2010963C as an “endurance allele” of elite athletes ( Ahmetov et al, 2009 ).…”

Mechanism of the Huangguoshu waterfall forest environment’s promotive effect on human health in Guizhou, China

“…According to the serological indexes, the waterfall forest environment notably improved the levels of endogenous GSH-Px and SOD in participants but reduced the level of MDA. Meanwhile, the levels of serum IL-1β, IL-6, and IL-10 were decreased after exposure to the waterfall forest environment, suggesting that the waterfall forest environment can reduce the level of inflammatory factors in the body (34). Serum TNF-α level has been shown to be elevated in patients with agingrelated diseases such as Alzheimer disease (35).…”