Raised levels of immunoglobulin G, A and M are associated with an increased risk of total and cause-specific mortality: the Vietnam Experience Study

Phillips, Anna C.; Drayson, Mark T.; Batty, G. David

doi:10.1136/jech-2014-204345

Cited by 13 publications

(10 citation statements)

References 27 publications

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“…This makes it plausible that in older adults, both low sIgA and high serum IgA can be related to increased mortality. Some recent studies have shown higher serum IgA values associated with increased mortality risk [ 20 , 41 , 43 ]. However, in these cases the authors conclude that this is likely to be due to reverse causation whereby extant disease is responsible for elevated IgA levels.…”

Section: Resultsmentioning

confidence: 99%

“…Certain types of kidney disease are also associated with abnormalities of the IgA system [ 19 ]. Recently, in a large study of Vietnam-era war veterans, we have found that higher levels of serum immunoglobulins, including IgA, were associated with around a two-fold increased risk of mortality from all-causes and ‘other’ causes (corresponding to deaths that were not ascribed to cardiovascular disease and cancer causes, largely comprising infectious diseases) [ 20 ]. On the other hand, severe serum IgA insufficiency which is inherited by up to 0.5% of the general population is also associated with higher mortality in the first 10–15 years from diagnosis in a Swedish population study [ 21 ] and has also been related to higher prevalence of coeliac disease, type I diabetes and other autoimmune diseases [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Salivary Immunoglobulin A Secretion Rate Is Negatively Associated with Cancer Mortality: The West of Scotland Twenty-07 Study

2015

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Immunoglobulins are essential for combating infectious disease although very high levels can indicate underlying pathology. The present study examined associations between secretory immunoglobulin A (sIgA) in saliva and mortality rates in the general population. Participants were 639 adults from the eldest cohort of the West of Scotland Twenty-07 Study aged 63 years at the time of saliva sampling in 1995. From unstimulated 2-minute saliva samples, saliva volume and S-IgA concentration were measured, and S-IgA secretion rate determined as their product. Mortality data were tracked for 19 years. Cox proportional hazard models were applied to compute hazard ratios (HR) for all-cause mortality from sIgA secretion rate. Associations were adjusted for gender, assay batch, household occupational group, smoking, medication usage, and self-reported health. There was a negative association between log sIgA secretion rate and all-cause mortality, HR = 0.81, 95%CI = 0.73–0.91, p < .001. Further analysis of specific causes of mortality revealed that the all-cause association was due to an underlying association with cancer mortality and in particular with cancers other than lung cancer. The HR for non-lung cancer was 0.68 (95%CI = 0.54 to 0.85) implying a 32% reduction in mortality risk per standard deviation rise in log sIgA secretion rate. Effects were stronger for men than women. For deaths from respiratory diseases, sIgA secretion had a non-linear relationship with mortality risk whereby only the very lowest levels of secretion were associated with elevated risk. SIgA concentration revealed a similar but weaker pattern of association. In the present study, higher secretion rates of sIgA were associated with a decreased risk of death from cancer, specifically non-lung cancer, as well as from respiratory disease. Thus, it appears that sIgA plays a protective role among older adults, and could serve as a marker of mortality risk, specifically cancer mortality.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Salivary Immunoglobulin A Secretion Rate Is Negatively Associated with Cancer Mortality: The West of Scotland Twenty-07 Study

2015

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“…High levels of IgG are associated with an elevated risk of death from all-cause mortality, but most importantly from infectious disease. 46 In addition, some auto-antibodies such as anti-GM-CSF 47 and anti-IFN-γ have been associated with CM in otherwise immunocompetent patients. 48 Hence, in addition to total IgG, it may also be useful to follow auto-antibodies specific for inflammatory cytokines during infection.…”

Section: Discussionmentioning

confidence: 99%

Clinical Immunophenotype at Disease Onset in Previously Healthy Patients With Cryptococcal Meningitis

Huang

Lin

et al. 2016

Medicine

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Cryptococcal meningitis (CM) is a global disease with significant morbidity and mortality. Although low peripheral blood cluster of differentiation 4 (CD4)+ cell counts are found to be related to a high burden of cryptococcus in HIV-infected patients, little is known about possible immune defects in previously healthy patients (PHPs). We performed a retrospective study of 41 CM patients treated from January 2005 to December 2014 who did not have HIV-infection. There were 33 PHPs and 8 not previously healthy patients (non-PHPs). We analyzed clinical test data pertaining to peripheral blood T cells, antibodies, inflammation markers, and cerebral spinal fluid (CSF) completed during the disease onset phase and 5 years following diagnosis. PHPs had significantly higher counts of cluster of differentiation 3 (CD3)+, cluster of differentiation 4 (CD4)+, and cluster of differentiation 45 (CD45)+ cells, and lower percentages of CD8+ cells than non-PHPs (P < 0.05). Measurements of inflammatory markers and immunoglobulin in blood were comparable except for lower immunoglobulin A (IgA) levels in non-PHPs (P = 0.0410). Examination of CSF revealed lower white blood cell (WBC) counts in non-PHPs. Five-year mortality in PHPs was higher than in non-PHPs (22.0% vs 12.5%) but this was not statistically significant (P > 0.05). Multivariate analysis revealed that higher immunoglobulin G (IgG) levels in serum during disease onset may be an independent predictor of mortality (P = 0.015). In conclusion, PHPs demonstrate an immunophenotype that is distinct from that of non-PHPs, leading to an improved understanding of the immunology of cryptococcal meningitis.

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“…[28] Several diseases can be diagnosed through the assessment of immunoglobulin levels in biofluids. [29][30][31] Unfortunately, the current state-of-the-art immunoglobulin assays are lengthy and complicated. Here, pooled plasma further characterized the clinical potential of VAIA (Figure 3C).…”

Section: Zuschriftenmentioning

confidence: 99%

Under‐5‐Minute Immunoblot Assays by Vortex Fluidic Device Acceleration

et al. 2022

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Unlocking the potential of personalized medicine in point-of-care settings requires a new generation of biomarker and proteomic assays. Ideally, assays could inexpensively perform hundreds of quantitative protein measurements in parallel at the bedsides of patients. This goal greatly exceeds current capabilities. Furthermore, biomarker assays are often challenging to translate from benchtop to clinic due to difficulties achieving and assessing the necessary selectivity, sensitivity, and reproducibility. To address these challenges, we developed an efficient (< 5 min), robust (comparatively lower CVs), and inexpensive (decreasing reagent use and cost by > 70 %) immunoassay method. Specifically, the immunoblot membrane is dotted with the sample and then developed in a vortex fluidic device (VFD) reactor. All assay steps-blocking, binding, and washing-leverage the unique thin-film microfluidics of the VFD. The approach can accelerate direct, indirect, and sandwich immunoblot assays. The applications demonstrated include assays relevant to both the laboratory and the clinic.

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Raised levels of immunoglobulin G, A and M are associated with an increased risk of total and cause-specific mortality: the Vietnam Experience Study

Abstract: In the present study, high levels of Ig are associated with an elevated risk of death from total and 'other' causes, mainly infectious disease. High levels of Ig, particularly IgG, may signal subclinical disease.

Cited by 13 publications

References 27 publications

Salivary Immunoglobulin A Secretion Rate Is Negatively Associated with Cancer Mortality: The West of Scotland Twenty-07 Study

Salivary Immunoglobulin A Secretion Rate Is Negatively Associated with Cancer Mortality: The West of Scotland Twenty-07 Study

Clinical Immunophenotype at Disease Onset in Previously Healthy Patients With Cryptococcal Meningitis

Under‐5‐Minute Immunoblot Assays by Vortex Fluidic Device Acceleration

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