Background: Increased prevalence of autoantibody Fab glycosylation has been demonstrated for several autoimmune diseases. Objectives: To study whether elevated Fab glycosylation is a common feature... Show moreBackground: Increased prevalence of autoantibody Fab glycosylation has been demonstrated for several autoimmune diseases. Objectives: To study whether elevated Fab glycosylation is a common feature of autoimmunity, this study investigated Fab glycosylation levels on serum IgG and its subclasses for autoantibodies associated with a range of different B cell- mediated autoimmune diseases, including rheumatoid arthritis, myasthenia gravis subtypes, pemphigus vulgaris, antineutrophil cytoplasmic antibody-associated vasculitis, systemic lupus erythematosus, anti-glomerular basement membrane glomerulonephritis, thrombotic thrombocytopenic purpura, and Guillain-Barre ⠁ syndrome. Methods: The level of Fab glycosylated IgG antibodies was assessed by lectin affinity chromatography and autoantigen-specific immunoassays. Results: In 6 of 10 autoantibody responses, in 5 of 8 diseases, the investigators found increased levels of Fab glycosylation on IgG autoantibodies that varied from 86% in rheumatoid arthritis to 26% in systemic lupus erythematosus. Elevated autoantibody Fab glycosylation was not restricted to IgG4, which is known to be prone to Fab glycosylation, but was also present in IgG1. When autoimmune diseases with a chronic disease course were compared with more acute autoimmune illnesses, increased Fab glycosylation was restricted to the chronic diseases. As a proxy for chronic autoantigen exposure, the investigators determined Fab glycosylation levels on antibodies to common latent herpes viruses, as well as to glycoprotein 120 in individuals who are chronically HIV-1-infected. Immunity to these viral antigens was not associated with increased Fab glycosylation levels, indicating that chronic antigen-stimulation as such does not lead to increased Fab glycosylation levels. Conclusions: These data indicate that in chronic but not acute B cell-mediated autoimmune diseases, disease-specific autoantibodies are enriched for Fab glycans. (J Allergy Clin Immunol 2023;151:16 46-54.) Show less
Voorend, C.G.N.; Oevelen, M. van; Nieberg, M.; Meuleman, Y.; Franssen, C.F.M.; Joosten, H.; ... ; POLDER Investigators 2021
Background: Older patients with advanced chronic kidney disease are at increased risk for a severe course of the coronavirus disease-2019 (COVID-19) and vulnerable to mental health problems. We... Show moreBackground: Older patients with advanced chronic kidney disease are at increased risk for a severe course of the coronavirus disease-2019 (COVID-19) and vulnerable to mental health problems. We aimed to investigate prevalence and associated patient (demographic and clinical) characteristics of mental wellbeing (health-related quality of life [HRQoL] and symptoms of depression and anxiety) before and during the COVID-19 pandemic in older patients with advanced chronic kidney disease.Methods: An ongoing Dutch multicentre prospective cohort study enrols patients of >= 70 years with an eGFR < 20 mL/min/1.73m(2) from October 2018 onward. With additional questionnaires during the pandemic (May-June 2020), disease-related concerns about COVID-19 and general anxiety symptoms were assessed cross-sectionally, and depressive symptoms, HRQoL, and emotional symptoms longitudinally.Results: The 82 included patients had a median age of 77.5 years (interquartile range 73.9-82.1), 77% were male and none had tested positive for COVID-19. Cross-sectionally, 67% of the patients reported to be more anxious about COVID-19 because of their kidney disease, and 43% of the patients stated that their quality of life was reduced due to the COVID-19 pandemic. Compared to pre-COVID-19, the presence of depressive symptoms had increased (11 to 22%; p = .022) and physical HRQoL declined (M = 40.4, SD = 10.1 to M = 36.1, SD = 10.4; p < .001), particularly in males. Mental HRQoL (M = 50.3, SD = 9.6 to M = 50.4, SD = 9.9; p = .913) and emotional symptoms remained similar.Conclusions: Older patients with advanced chronic kidney disease suffered from disease-related anxiety about COVID-19, increased depressive symptoms and reduced physical HRQoL during the COVID-19 pandemic. The impact of the pandemic on this vulnerable patient group extends beyond increased mortality risk, and awareness of mental wellbeing is important. Show less
Purpose Unidentified cognitive decline and other geriatric impairments are prevalent in older patients with advanced chronic kidney disease (CKD). Despite guideline recommendation of geriatric... Show morePurpose Unidentified cognitive decline and other geriatric impairments are prevalent in older patients with advanced chronic kidney disease (CKD). Despite guideline recommendation of geriatric evaluation, routine geriatric assessment is not common in these patients. While high burden of vascular disease and existing pre-dialysis care pathways mandate a tailored geriatric assessment, no consensus exists on which instruments are most suitable in this population to identify geriatric impairments. Therefore, the aim of this study was to propose a geriatric assessment, based on multidisciplinary consensus, to routinely identify major geriatric impairments in older people with advanced CKD. Methods A pragmatic approach was chosen, which included focus groups, literature review, inventory of current practices, an expert consensus meeting, and pilot testing. In preparation of the consensus meeting, we composed a project team and an expert panel (n = 33), drafted selection criteria for the selection of instruments, and assessed potential instruments for the geriatric assessment. Results Selection criteria related to general geriatric domains, clinical relevance, feasibility, and duration of the assessment. The consensus-assessment contains instruments in functional, cognitive, psychological, somatic, patient preferences, nutritional status, and social domains. Administration of (seven) patient questionnaires and (ten) professional-administered instruments, by nurse (practitioners), takes estimated 20 and 40 min, respectively. Results are discussed in a multidisciplinary meeting including at least nephrology and geriatric expertise, informing nephrology treatment decisions, and follow-up interventions among which comprehensive geriatric assessment. Conclusion This first multidisciplinary consensus on nephrology-tailored geriatric assessment intent to benefit clinical care and enhance research comparability for older patients with advanced CKD.Key Summary pointsAim To propose a consensus-based geriatric assessment for optimizing both routine care and research in older patients with advanced chronic kidney disease. Findings Using a pragmatic approach, we reached consensus on a suitable nephrology-tailored geriatric assessment to routinely identify major geriatric impairments in older patients with advanced chronic kidney disease. This geriatric assessment contains instruments in functional, cognitive, psychological, somatic, patient preferences, nutritional status, and social domains, and can be administered with patient questionnaires and professional-administered instruments by nurse (practitioners) in approximately 20 and 40 minutes, respectively. Message We propose a consensus test set for standardized nephrology-tailored geriatric assessment, which is currently being implemented in multiple hospitals and studies, to benefit clinical care for older patients with advanced chronic kidney disease and enhance research comparability. Show less
Faria, B.; Costa, M.G. da; Poppelaars, F.; Franssen, C.F.M.; Pestana, M.; Berger, S.P.; ... ; Seelen, M.A. 2019
Background: Intravenous (IV) iron is widely used to treat anemia in chronic kidney disease patients. Previously, iron formulations were shown to induce immune activation in-vitro. The current study... Show moreBackground: Intravenous (IV) iron is widely used to treat anemia in chronic kidney disease patients. Previously, iron formulations were shown to induce immune activation in-vitro. The current study aimed to investigate the effect of IV iron on complement activation in-vivo, and whether this subsequently induces inflammation and/or oxidative stress.Methods: Two distinct patient groups were included: 51 non-dialysis and 32 dialysis patients. The non-dialysis group received iron sucrose or ferric carboxymaltose, based on physicians' choice. Plasma samples were collected prior to and 1 h after completion of IV iron infusion. The dialysis group received iron sucrose exclusively. Plasma samples were collected at the start and end of two consecutive hemodialysis sessions, one with and one without IV iron. Finally, plasma levels of MBL, C1q, properdin, factor D, sC5b-9, MPO, PTX3 were assessed by ELISA.Results: In the non-dialysis group, sC5b-9 levels significantly increased after IV iron by 32%, while levels of factor D and MBL significantly dropped. Subgroup analysis demonstrated that iron sucrose induced complement activation whereas ferric carboxymaltose did not. In the dialysis group, levels of sC5b-9 significantly increased by 46% during the dialysis session with IV iron, while factor D levels significantly fell. Furthermore, the relative decrease in factor D by IV iron correlated significantly with the relative increase in sC5b-9 by IV iron. MPO levels rose significantly during the dialysis session with IV iron, but not in the session without iron. Moreover, the relative increase in MPO and sC5b-9 by IV iron correlated significantly. PTX3 levels were not affected by IV iron.Conclusions: Iron sucrose but not ferric carboxymaltose, results in complement activation possibly via the lectin and alternative pathway partially mediating oxidative stress but not inflammation. Show less
