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

Abstract

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.

Evaluation of Circulating Chitotriosidase Activity in Children with Obesity

“…This result suggests an extent of the inflammation with the grade of obesity based on previous findings that have indicated an association between CHIT1 activity and in-flammatory conditions [14,15,[57][58][59], probably mainly due to its biological role in reflecting macrophage activation [14]. The increasing CHIT1 activity has been attributed to macrophage activation in adults with obesity-driven complications and in children with glucose intolerance [23,25].…”

“…In a population-based study conducted in a Brazil, Tamanaha et al [24] reported higher CHIT1 serum levels in adults with obesity than in adults with normal BMI. Increased plasma CHIT1 levels were also reported in children with immunodeficiency and lysosomal storage disorders [25,26]. Kabaro glu et al reported higher plasma CHIT1 levels in children with obesity and impaired glucose tolerance than those without impaired glucose tolerance [23].…”

Clinical Significance of Chitotriosidase in Outpatients with Advanced Heart Failure

“…10 In addition, increased levels in plasma have been shown in diseases such as chronic lung diseases, tuberculosis, sarcoidosis, multiple sclerosis, malignancy, thalassemia, familial Mediterranean fever, Alzheimer's and stroke. 11 According to recent studies, CHIT may play a role in innate immunity and may act as an immunomodulator indirectly in antigen presentation and induction of cellmediated immunity. 12 The role of CHIT in the development and progression of atherosclerosis has been supported by many studies.…”

“…Therefore, CHIT activity measurement is used as a biochemical marker in lysosomal storage diseases such as Gaucher disease and Nieman Pick, in which macrophage accumulation and activity increase 10. In addition, increased levels in plasma have been shown in diseases such as chronic lung diseases, tuberculosis, sarcoidosis, multiple sclerosis, malignancy, thalassemia, familial Mediterranean fever, Alzheimer's and stroke 11. According to recent studies, CHIT may play a role in innate immunity and may act as an immunomodulator indirectly in antigen presentation and induction of cell-mediated immunity 12…”