Accelerated atherosclerosis in patients with common variable immunodeficiency: Is it overlooked or absent?

Uçar, Ramazan; Arslan, Şevket; Türkmen, Kültiğin; Çalışkaner, Ahmet Zafer

doi:10.1016/j.mehy.2015.07.002

Cited by 8 publications

(11 citation statements)

References 21 publications

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“…A rational line of reasoning could suggest the chronic systemic inflammation found in CVID patients would lead to increased incidence of cardiovascular disease in this group. However, no clear evidence has been found to substantiate this hypothesis 29 . American and European registry data have rather identified lung disease and autoimmune manifestations as the most prevalent complications to CVID 7,30 .…”

Section: Discussionmentioning

confidence: 95%

“…American and European registry data have rather identified lung disease and autoimmune manifestations as the most prevalent complications to CVID 7,30 . It has however been speculated that atherosclerosis is present but does not amount to clinical levels substantial enough to cause cardiovascular disease due to the reduced life expectancy in CVID patients with non-infectious complications 29 .…”

Section: Discussionmentioning

confidence: 99%

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Impaired HDL Function Amplifies Systemic Inflammation in Common Variable Immunodeficiency

Macpherson

Halvorsen

Yndestad

et al. 2019

Sci Rep

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Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency, characterized by inadequate antibody responses and recurrent bacterial infections. Paradoxically, a majority of CVID patients have non-infectious inflammatory and autoimmune complications, associated with systemic immune activation. Our aim was to explore if HDL, known to have anti-inflammatory properties, had impaired function in CVID patients and thereby contributed to their inflammatory phenotype. We found reduced HDL cholesterol levels in plasma of CVID patients compared to healthy controls, particularly in patients with inflammatory and autoimmune complications, correlating negatively with inflammatory markers CRP and sCD25. Reverse cholesterol transport capacity testing showed reduced serum acceptance capacity for cholesterol in CVID patients with inflammatory and autoimmune complications. They also had reduced cholesterol efflux capacity from macrophages to serum and decreased expression of ATP-binding cassette transporter ABCA1. Human HDL suppressed TLR2-induced TNF release less in blood mononuclear cells from CVID patients, associated with decreased expression of transcriptional factor ATF3. Our data suggest a link between impaired HDL function and systemic inflammation in CVID patients, particularly in those with autoimmune and inflammatory complications. This identifies HDL as a novel therapeutic target in CVID as well as other more common conditions characterized by sterile inflammation or autoimmunity.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Impaired HDL Function Amplifies Systemic Inflammation in Common Variable Immunodeficiency

Macpherson

Halvorsen

Yndestad

et al. 2019

Sci Rep

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“…So, atherosclerotic changes and endothelial dysfunction may be overlooked. Ucar et al 6 speculated that the immunomodulatory effect of regular IVIg treatment in CVID patients might supress IgG-dependent inflammation and thus protect endothelial cells from excessive cytokine exposure.…”

Section: Discussionmentioning

confidence: 99%

Chitotriosidase enzyme activity: is this a possible chronic inflammation marker in children with common variable immunodeficiency and early atherosclerosis?

et al. 2017

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Background Common variable immunodeficiency is a rare clinically symptomatic primary immunodeficiency disorder which manifests a wide variability of symptoms, complications. Atherosclerosis in common variable immunodeficiency patients has not been investigated yet contrary to other severe clinical complications. We aimed to investigate the chitotriosidase enzyme's role as an inflammation and atherosclerosis marker in paediatric common variable immunodeficiency patients. Methods Common variable immunodeficiency patients (n = 24) and healthy controls (n = 23) evaluated for chitotriosidase activity with other inflammation markers (hsCRP, myeloperoxidase, serum amyloid A, ferritin), lipid profile and echocardiographic findings (carotid artery intima media thickness - cIMT, brachial artery flow-mediated vazodilatation - FMD%). Results In patients, the mean chitotriosidase activity (8.98 ± 6.28) was significantly higher than the controls (5.17 ± 3.42) ( P = 0.014). Chitotriosidase showed positive relation with hs-CRP ( P = 0.011) and SAA ( P = 0.011) but had no relation with ferritin ( P = 0.155), HDL ( P = 0.152) or LDL-cholesterol ( P = 0.380). Mean cIMT increased in patients compared with the controls ( P < 0.001) but did not show any relation with chitotriosidase ( P = 0.546). FMD% decreased in patients ( P < 0.001) also showing no relation with chitotriosidase ( P = 0.298). Ventricular myocardial performance indexes had no significant difference, but RVEF% decreased in patients ( P = 0.043). Conclusions High chitotriosidase activity in common variable immunodeficiency patients demonstrated in vivo the presence of activated macrophages indicating ongoing inflammation. Echocardiographic diastolic functional deficiency, increased cIMT and decreased FMD% may be accepted as early atherosclerotic findings, but none of them showed relationship with chitotriosidase activities.

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“…On the other hand, it was thought that atherosclerosis and related diseases could be overlooked in these patients due to chronic respiratory infections (pneumonia, bronchiectasis, etc. ), gastrointestinal system infections, autoimmune diseases and malignant diseases which are more common in early ages (23). As life expectancy was lower in this patient group, atherosclerotic cardiovascular diseases were thought to not display any clinical symptoms.…”

Section: Discussionmentioning

confidence: 80%

“…In a comprehensive study, the age of mortality was shown to be between 40 and 50 years. However, with current immunoglobulin therapies and advanced antibiotic technologies, it is thought that the rate of patients presenting with cardiovascular diseases will increase in the near future (23,24). Another hypothesis was described as follows: "Endothelial dysfunction and endothelial inflammation in atherosclerosis cannot develop due to chronic immune dysregulation and immunodeficiency or the risk of atherosclerosis in these patients is similar in healthy individuals due to received immunoglobulin treatments" (23).…”

Section: Discussionmentioning

confidence: 99%

Electrocardiographic Alterations in Patients with Common Variable Immune Deficiency

Alsancak¹,

Çölkesen²

2020

Istanbul Med J

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Amaç: Ortak değişken immün yetmezlik (CVID), antikor eksikliği sendromları arasında en heterojen gruptur, ancak kardiyovasküler sistem üzerindeki etkileri henüz net bir şekilde tanımlanamamıştır. Burada, bu hastalığın olası aritmojenik etkilerini, elektrokardiyografi ile değerlendirmeyi amaçladık. Yöntemler: Çalışmaya 30 CVID hastası ile yaş ve komorbiditeleri eşleşen 30 gönüllü kontrol grubu dahil edildi. Tüm katılımcıların elektrokardiyografik ve ekokardiyografik değerleri kaydedildi. QRS, QT, Tp-e manuel olarak ölçüldü. QTc, Bazett formülü kullanılarak hesaplandı. Daha sonra, Tp-e/QT, Tp-e/QTc, QT/QRS ve QTc/QRS oranları hesaplandı ve gruplar arasında karşılaştırılma yapıldı. Bulgular: CVID grubunda PR aralığı ve P dalga dispersiyonu daha yüksek bulundu. Ayrıca, QT aralığı ve düzeltilmiş QT aralığı, T peak-to-end interval, CVID kolunda daha yüksekti ve QT/QRS oranı ile elde edilen kardiyak elektrofizyolojik denge indeksi değeri CVID grubunda da daha yüksekti. CVID grubunda P terminal kuvveti olan hasta sayısı da daha fazla idi. Sonuç: Bu çalışma sonucunda, CVID hastalarının normal sağlıklı bireylere göre aritmi gelişme sıklığının daha yüksek olabileceği bulunmuştur.

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Accelerated atherosclerosis in patients with common variable immunodeficiency: Is it overlooked or absent?

Cited by 8 publications

References 21 publications

Impaired HDL Function Amplifies Systemic Inflammation in Common Variable Immunodeficiency

Impaired HDL Function Amplifies Systemic Inflammation in Common Variable Immunodeficiency

Chitotriosidase enzyme activity: is this a possible chronic inflammation marker in children with common variable immunodeficiency and early atherosclerosis?

Electrocardiographic Alterations in Patients with Common Variable Immune Deficiency

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