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Prevalence of Elevated Serum IgG4 Level among Patients Diagnosed or Suspected with Cardiovascular Disorders.

ABSTRACT: Immunoglobulin G4 (IgG4)-related disease, that is characterized by the elevation of circulating IgG4 level and the tissue-in?ltration of IgG4-positive plasma cells, can target the cardiovascular tissue, although the diagnosis of IgG4-related cardiovascular lesion is not easy owing to the substantial risk for the tissue sampling. We herein examined the serum IgG4 levels among cardiac patients. In patients who were admitted to the cardiology department (n=477) and those who underwent computed tomography coronary artery angiography (n=401), elevated serum IgG4 level (?135?mg/dL) was found 23 (4.8%) and 17 (4.2%), respectively. However, among those with elevated serum IgG4, only two patients could be clinicopathologically diagnosed with IgG4-related disease. Cardiovascular organ involvement may aggravate the prognosis of IgG4-related disease which in general not life-threatening. Considering that the non-negligible prevalence of high IgG4 level among cardiac patients who were not diagnosed with IgG4-related disease, however, physicians should not count too much on the serum IgG4 levels for the diagnosis of IgG4-related cardiovascular lesions, especially when histopathologic ?ndings are not available, or when other-tissue involvement of IgG4-related disease is not apparent. (This is a translation of J Jpn Coll Angiol 2017; 57: 91-98.).

SUBMITTER: Ishizaka N

PROVIDER: S-EPMC6326049 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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Prevalence of Elevated Serum IgG4 Level among Patients Diagnosed or Suspected with Cardiovascular Disorders.

Ishizaka Nobukazu N Fujinaga Yasunari Y Hourai Ryoto R Fujisaka Tomohiro T Sohmiya Koichi K

Annals of vascular diseases 20181201 4

Immunoglobulin G4 (IgG4)-related disease, that is characterized by the elevation of circulating IgG4 level and the tissue-inﬁltration of IgG4-positive plasma cells, can target the cardiovascular tissue, although the diagnosis of IgG4-related cardiovascular lesion is not easy owing to the substantial risk for the tissue sampling. We herein examined the serum IgG4 levels among cardiac patients. In patients who were admitted to the cardiology department (n=477) and those who underwent computed tomo ...[more]

PMID: 30637005

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Project description:Background:Recent studies have suggested that cell death might be involved in the pathophysiology of metabolic disorders. The cytokeratin 18 (CK18) fragment, as a cell death marker, plays an important role in nonalcoholic fatty liver disease (NAFLD). However, only a limited number of studies have found elevated serum levels of CK18 in patients with type 2 diabetes. Moreover, no studies have been conducted yet to investigate the role of CK18 in hypertension or dyslipidemia. In particular, CK18 M65ED is a more sensitive marker of cell death, and its role in cardiometabolic disorders has not been revealed yet. Methods:A total of 588 subjects were enrolled from the local communities of Shanghai. Serum CK18 M65ED were determined using the enzyme-linked immunosorbent assay. A cardiometabolic disorder was identified by the presence of at least one of the components including overweight or central obesity, diabetes, dyslipidemia, and hypertension. Results:Subjects with cardiometabolic disorders exhibited significantly higher serum levels of CK18 M65ED than those without cardiometabolic disorders (197.36 (121.13-354.50) U/L versus 83.85 (52.80-153.75) U/L, respectively, P < 0.001). Increased serum CK18 M65ED quartiles were associated with the increased prevalence of cardiometabolic disorders and its components (P < 0.001 for all components). Multiple stepwise regression analysis also revealed that diastolic blood pressure, glycated hemoglobin A1c, alanine transaminase, and high-density lipoprotein cholesterol were independently correlated with serum CK18 M65ED levels (all P < 0.01). In addition, logistic regression analysis showed that the serum CK18 M65ED levels were positively correlated with cardiometabolic disorders and in an independent manner. Further, CK18 M65ED was revealed to be an indicator of cardiometabolic disorders in a NAFLD-independent manner. Conclusions:Elevated levels of CK18 M65ED, a sensitive cell death marker, were independently and positively correlated with cardiometabolic disorders, even after the adjustment for the presence of NAFLD and other cardiovascular risk factors.

Project description:Simple Summary Immunoglobulin is a group of proteins participating in process of inflammation. One of its subtypes is Immunoglobulin Gamma-4 (IgG4) which is related to a rare disease called IgG4-related disease and characterized by a process of fibrosis—deposition of fibers in different organs and inflammation, resulting in tissue damage and dysfunction including the heart muscle and vessels. There is a paucity of information regarding the potential link between of IgG4 and cardiovascular diseases. The purpose of this study is to assess the serum levels of IgG4 in patients with dilated cardiomyopathy (DCM), a disease characterized by cardiac muscle dysfunction of ischemic and non-ischemic origin. Ischemic heart disease is a disease in which heart muscle is damaged by inappropriate blood supply caused by blood vessel obstruction and may cause heart muscle dysfunction. Ninety-eight patients with ischemic and non-ischemic cardiomyopathy were included in this study. The serum concentrations of IgG4 were measured. Patients with DCM had significantly higher levels of IgG4 compared with the healthy control group (77.4 ± 64.0 vs. 50.3 ± 28.8 mg/dL, p < 0.01). Although there was no difference in the total IgG levels in patients with ischemic DCM, the serum concentrations of IgG4 were significantly higher than the corresponding values in the control group (89.8 ± 67.3 vs. 50.3 ± 28.8 mg/dL, p < 0.01). In conclusion, we found that patients with ischemic cardiomyopathy had increased blood levels of IgG4. Additional studies with a larger number of patients are needed to support and explain this finding. Abstract (1) Background: Immunoglobulin gamma subclass 4 (IgG4) is a serum protein belonging to the immunoglobulin superfamily. It has a central role in certain immune-mediated conditions defined as IgG4-related disease. There is a paucity of data regarding the potential association of IgG4 and cardiovascular diseases. Our aim is to study the serum levels of IgG4 in patients with ischemic and non-ischemic dilated cardiomyopathy (DCM). (2) Methods: patients with ischemic and non-ischemic DCM were included in this study. Non-ischemic DCM was defined as a left ventricular ejection fraction (LVEF) < 40% without coronary artery disease (CAD). Ischemic DCM was defined as a LVEF < 40% and proven CAD. The serum concentrations of IgG4 were measured by turbidimetry. (3) Results: Overall 98 patients with cardiomyopathy had significantly higher levels of IgG4 compared with the control group (77.4 ± 64.0 vs. 50.3 ± 28.8 mg/dL, p < 0.01). Although there was no difference in the total IgG levels in patients with ischemic DCM, the serum concentrations of IgG4 were significantly higher than the corresponding values in the control group (89.8 ± 67.3 vs. 50.3 ± 28.8 mg/dL; interquartile ranges: 40.4–126.5 vs. 31.8–66.8 mg/dL, p < 0.01). This was altered by gender and smoking. (4) Conclusions: The patients with ischemic DCM had increased serum concentrations of IgG4. Future studies are warranted to explore the potential role of an IgG4-mediated process in patients with heart failure with reduced LVEF.

Dataset Information

Prevalence of Elevated Serum IgG4 Level among Patients Diagnosed or Suspected with Cardiovascular Disorders.

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Prevalence of Elevated Serum IgG4 Level among Patients Diagnosed or Suspected with Cardiovascular Disorders.

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