Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts

Ajeganova, Sofia; Humphreys, Jennifer; Verheul, Marije K.; Steenbergen, H.W. van; Nies, Jessica A B van; Hafström, Ingiäld; Svensson, Björn; Huizinga, Tom W J; Trouw, Leendert A.; Verstappen, Suzanne M M; Mil, Annette H M van der Helm-van

doi:10.1136/annrheumdis-2015-208579

Cited by 58 publications

(62 citation statements)

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“…Based upon previous studies, such events could be related to a chronic low-grade inflammatory state through sustained activation of the TLR2/TLR4/CD14 complex and production of pro-inflammatory cytokines (14, 18, 21, 24, 38), associations with elevated high-sensitivity C-reactive protein and uric acid levels (23, 25), impairment of HDL function (10–13, 16, 17), interference with basal heart rate regulation (22, 24, 25) or B-cell epitope spreading (39). Other pathophysiological mechanisms, other than those currently ascribed to anti-apoA-1 IgG could also be involved, in the same way that multiple molecular pathways underlie the associations of other autoantibodies with all-cause mortality in the community (7, 9, 40, 41). These challenging points will have to be investigated in future clinical and translational research efforts.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple studies have established the relationship between a chronic inflammatory state due to clinical or quiescent autoimmunity and poor outcomes in various clinical settings (5, 6). Marking sustained B-cell activation, presence of autoantibodies specifically represents a signature of humoral autoimmunity, which can drive disease pathogenesis even in the absence of overt clinical AD (7–9). …”

Section: Introductionmentioning

confidence: 99%

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Anti-Apolipoprotein A-1 IgG Predict All-Cause Mortality and Are Associated with Fc Receptor-Like 3 Polymorphisms

et al. 2017

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BackgroundAutoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) have emerged as an independent biomarker for cardiovascular disease and mortality. However, their association with all-cause mortality in the community, as well as their genetic determinants, have not been studied.ObjectiveTo determine whether anti-apoA-1 IgG: (a) predict all-cause mortality in the general population and (b) are associated with single-nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS).MethodsClinical, biological, and genetic data were obtained from the population-based, prospective CoLaus study, including 5,220 participants (mean age 52.6 years, 47.3% men) followed over a median duration of 5.6 years. The primary study outcome was all-cause mortality.ResultsAfter multivariate adjustment, anti-apoA-1 IgG positivity independently predicted all-cause mortality: hazard ratio (HR) = 1.54, 95% confidence interval (95% CI): 1.11–2.13, P = 0.01. A dose–effect relationship was also observed, each SD of logarithmically transformed anti-apoA-1 IgG being associated with a 15% increase in mortality risk: HR = 1.15, 95% CI: 1.02–1.28, P = 0.028. The GWAS yielded nine SNPs belonging to the Fc receptor-like 3 (FCRL3) gene, which were significantly associated with anti-apoA-1 IgG levels, with the lead SNP (rs6427397, P = 1.54 × 10−9) explaining 0.67% of anti-apoA-1 IgG level variation.ConclusionAnti-apoA-1 IgG levels (a) independently predict all-cause mortality in the general population and (b) are linked to FCRL3, a susceptibility gene for numerous autoimmune diseases. Our findings indicate that preclinical autoimmunity to anti-apoA-1 IgG may represent a novel mortality risk factor.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-Apolipoprotein A-1 IgG Predict All-Cause Mortality and Are Associated with Fc Receptor-Like 3 Polymorphisms

et al. 2017

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“…The role of anti-CCP positivity in atherosclerosis is supported by some studies showing that patients anti-CCP positive had increased risk of CV death that correlated with higher levels of proinflammatory cytokines such as TNFα and interleukin 6 (IL-6) [6]. If anti-CCP positivity plays a direct role in the development of atherosclerosis or if it represents only marker of proinflammatory state resulting in atherosclerotic process in these patients is still unknown.…”

Section: Inflammatory Markersmentioning

confidence: 96%

“…Excess mortality in RA has been seen in CV disease (31 %), pulmonary fibrosis (4 %), and lymphoma (2.3 %) [4]. Baseline predictors of mortality in patients with RA have been reported male gender, older age, poor function, lower socio-economic status, extra-articular manifestations, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) positivity, higher inflammatory parameters, and glucocorticoid therapy [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Cardiac Impairment in Rheumatoid Arthritis and Influence of Anti-TNFα Treatment

Lazúrová

Tomáš

2016

Clinic Rev Allerg Immunol

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There is evidence that rheumatoid arthritis (RA) is associated with higher overall and cardiovascular (CV) morbidity and mortality as compared with general population. Increased prevalence of traditional risk factors and chronic inflammation, that has been recognized as independent CV risk factor, may play an important role in atherosclerosis and subsequently ischemic heart disease development. However, myocardial dysfunction as a result of chronic inflammation and secondarily myocardial fibrosis markedly participates on heart failure development. Proinflammatory cytokines, such as C-reactive protein, tumor necrosis factor alpha (TNFα), interleukins 1 and 6, that are markedly increased in RA, play a role in the acceleration of atherosclerosis as well as myocardial fibrosis development. Several studies documented that increased CV risk was associated with seropositivity, disease activity score, citrullination, and duration of RA. Early detection of heart dysfunction is based on echocardiographic detection of diastolic dysfunction resulting from myocardial inflammation and fibrosis. Some studies showed also higher prevalence of left ventricular systolic dysfunction and increased prevalence of cardiac arrhythmias as compared to non-RA population. There are still controversies on the impact of NT-proBNP in predicting cardiac impairment in RA patients. Some authors consider it to be a sensitive noninvasive predictor of subclinical CV disease in these patients and also a predictor of all-cause mortality independently on traditional CV risk factors. However, the correlation with parameters of cardiac function was confirmed only in a few studies. The impact of biological treatment on progression of atherosclerosis and heart failure is still controversial and seems to be not harmful in young patients with normal left ventricular function. The effect of biologics, especially anti-TNFα drugs, is probably related to the cardiac function before treatment. Larger prospective clinical, echocardiographic, and magnetic resonance studies are needed.

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“…Subacute-acute, hyperacute, or even catastrophic and fulminant respiratory events occur in the ambit of almost all classic connective tissue disorders (CTDs); they may share systemic life-threatening manifestations, may precipitously lead to respiratory failure - in most cases requiring ventilatory support - as well as a combination of specific therapeutic measures, and in most affected patients constitute the devastating end-of-life event [1,2,3,4,5,6,7,8,9,10]. …”

Section: Introductionmentioning

confidence: 99%

Acute Respiratory Events in Connective Tissue Disorders

Papiris¹,

Manali²,

Kolilekas³

et al. 2016

Respiration

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Subacute-acute, hyperacute, or even catastrophic and fulminant respiratory events occur in almost all classic connective tissue disorders (CTDs); they may share systemic life-threatening manifestations, may precipitously lead to respiratory failure requiring ventilatory support as well as a combination of specific therapeutic measures, and in most affected patients constitute the devastating end-of-life event. In CTDs, acute respiratory events may be related to any respiratory compartment including the airways, lung parenchyma, alveolar capillaries, lung vessels, pleura, and ventilatory muscles. Acute respiratory events may also precipitate disease-specific extrapulmonary organ involvement such as aspiration pneumonia and lead to digestive tract involvement and heart-related respiratory events. Finally, antirheumatic drug-related acute respiratory toxicity as well as lung infections related to the rheumatic disease and/or to immunosuppression complete the spectrum of acute respiratory events. Overall, in CTDs the lungs significantly contribute to morbidity and mortality, since they constitute a common site of disease involvement; a major site of infections related to the ‘mater' disease; a major site of drug-related toxicity, and a common site of treatment-related infectious complications. The extreme spectrum of the abovementioned events, as well as the ‘vicious' coexistence of most of the aforementioned manifestations, requires skills, specific diagnostic and therapeutic means, and most of all a multidisciplinary approach of adequately prepared and expert scientists. Avoiding lung disease might represent a major concern for future advancements in the treatment of autoimmune disorders.

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Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts

Abstract: The presence of RF in patients with RA associates with an increased overall mortality rate. Cause-specific mortality rates differed between autoantibodies: ACPA associates with increased cardiovascular death and RF with death related to neoplasm and respiratory disease.

Cited by 58 publications

References 41 publications

Anti-Apolipoprotein A-1 IgG Predict All-Cause Mortality and Are Associated with Fc Receptor-Like 3 Polymorphisms

Anti-Apolipoprotein A-1 IgG Predict All-Cause Mortality and Are Associated with Fc Receptor-Like 3 Polymorphisms

Cardiac Impairment in Rheumatoid Arthritis and Influence of Anti-TNFα Treatment

Acute Respiratory Events in Connective Tissue Disorders

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