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Serum levels of IgG4 and soluble interleukin-2 receptor in patients with abdominal and thoracic aortic aneurysm who undergo coronary angiography
Atherosclerosis 221 (2012) 602–603
Contents lists available at SciVerse ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Letter to the Editor Serum levels of IgG4 and soluble interleukin-2 receptor in patients with abdominal and thoracic aortic aneurysm who undergo coronary angiography Keywords: IgG4-related systemic sclerosing disease Inflammation Aortic aneurysm Coronary artery disease Biomarkers
To the Editor Since Hamano et al. reported the infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in autoimmune pancreatitis [1], an IgG4-related clinicopathological condition is now recognized in a wide variety of organs including endocrine, urinary, and cardiovascular systems [2,3]. Inflammatory abdominal aortic aneurysm is a condition that shows dense periaortic fibrosis containing infiltrated inflammatory cells, and this relatively rare disorder is, albeit not always, IgG4-related [4]. It should be noted, however, that periaortic infiltration of IgG4-positive plasma cells may be observed in aortic aneurysm of an atherosclerotic [5], as well as an inflammatory nature. It has increasingly been recognized that IgG4-related perivascular immune inflammation can be observed not only in large vessels, such as aorta, but also in smaller-sized vessels such as coronary arteries [6–8]. In the current study, we measured serum levels of not only IgG4 but also soluble interleukin-2 receptor (sIL-2R), another marker of lymphocytic activation, which was because several previous studies suggested the association between sIL-2R and coronary artery disease [9–11]. In addition, a recent study showed that elevation of serum sIL-2R levels was observed in all patients (n = 9) with IgG4-related lymphadenopathy [12], although physiological relevance of elevation of sIL-2R in IgG4-related disease remains unclear. We have also recently shown that serum IgG4 and sIL2R levels were higher in patients with coronary artery stenosis among patients who were naïve for coronary artery interventions [13]. Intriguingly, the association between these biomarkers and coronary artery stenosis was in part independent of other atherosclerotic risk factors. In that study, however, 40 of the 286 patients enrolled were known to have aortic aneurysm; therefore, it might be questioned whether the observed relationship could be explained by the association between aortic aneurysm and IgG4. Here, after increasing the sample size, we set out to assess this point. The study was approved by The Ethical Committee of University of Tokyo, Tokyo, Japan. Written informed consent was obtained from all subjects. We enrolled 571 patients who underwent coronary angiography between 2005 and 2009, and, among them, 86 patients had aortic aneurysm (abdominal, 65, and thoracic, 37), of 0021-9150/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2012.01.038
which one was diagnosed as inflammatory aortic aneurysm with serum IgG4 levels of 115.0 mg/dL and sIL-2R levels of 592 U/mL. The exclusion criteria were acute myocardial infarction, and lack of informed consent for study enrollment. Unlike our preceding paper [13], patients who had a history of coronary interventions were not excluded from this study population (percutaneous coronary interventions 171; coronary artery bypass surgery 50). Serum levels of IgG4 were determined by turbidimetry and those of sIL2R were measured by enzyme-linked immunosorbent assay (SRL, Tokyo, Japan). A summary of the data of patients is provided in Table 1. The mean age was slightly, but significantly, higher, and male gender was more prevalent in patients with aortic aneurysm. The correlation coefficient between age and serum IgG4 was −0.044 (P = 0.302), and that between age and serum sIL-2R was 0.149 (P < 0.001) in this study population. Neither serum levels of IgG4 nor those of sIL-2R differed significantly between patients with and without aortic aneurysm. We then compared these biomarkers after subdividing patients according to the presence or absence of the coronary artery disease. Among 409 patients who had significant coronary artery disease, 51 patients had, and 358 patients did not have, aortic aneurysm. Serum levels of IgG4 (median 37.4 mg/dL, interquartile range [IR] 21.2–59.5) and sIL-2R (median 414 U/mL,
Table 1 Baseline characteristics of the study patients. Variables
AA group (n = 86)
no-AA group (n = 485)
Male gender, n (%) Age, years BMI, kg/m2 Systolic BP, mmHg Diastolic BP, mmHg The median of IgG4, mg/dL (IR) The median of sIL-2R, U/mL (IR) Old myocardial infarction, n (%) Congestive heart failure, n (%) Renal failure on hemodialysis, n (%) Hypertension, n (%) Dyslipidemia, n (%) Diabetes, n (%) Arteriosclerosis obliterans, n (%) Valvular heart disease, n (%) Smoking
72 (83.7) 69.3 ± 11.3 23.2 ± 3.7 127 ± 15 73 ± 11 36.6 (21.2–64.9) 384 (312–516) 11 (12.8) 8 (9.3) 1 (1.2)
352 (72.6) 66.4 ± 10.1 24.0 ± 3.5 131 ± 19 74 ± 13 32.5 (17.1–56.4) 374 (289–508) 106 21.9) 65 (13.4) 17 (3.5)
72 83.7) 36 (41.9) 15 (17.4) 5 (5.8)
408 (84.1) 328 (67.6) 226 (46.6) 35 (7.2)
4 (4.7)
39 (8.0)
Never, n (%)
22 (25.6)
172 (35.5)
Former, n (%)
47 (54.7)
230 (47.4)
Current, n (%)
17 (19.8)
83 (17.1)
P value 0.029 0.020 0.064 0.032 0.794 0.245 0.429 0.055 0.291 0.252 0.925 <0.001 <0.001 0.639 0.272 0.204
Values are presented as the mean ± standard deviation unless described otherwise. AA, BMI and BP indicate aortic aneurysm, body mass index and blood pressure, respectively. IR indicates interquartile range.
Letter to the Editor / Atherosclerosis 221 (2012) 602–603
IR 334–553) in patients with aortic aneurysm did not significantly differ from those in patients without aortic aneurysm (IgG4, median 34.1 mg/dL, IR 18.1–58.8, P = 0.602; sIL-2R, median 392 U/mL, IR 303–524, P = 0.176, by Mann–Whitney test). Among 162 patients who did not have significant coronary artery disease, 35 patients had, and 127 patients did not have, aortic aneurysm. Serum levels of IgG4 (median 33.7 mg/dL, IR 18.1–68.4) and sIL-2R (median 356 U/mL, IR 274–422) in patients with aortic aneurysm, again, did not significantly differ from those in patients without aortic aneurysm (IgG4, median 28.5 mg/dL, IR 14.9–45.7, P = 0.112; sIL2R, median 317 U/mL, IR 260–450, P = 0.460). It was found that 42 patients (8.7%) in the non-aneurysm group and 9 patients (10.5%) in the aneurysm group had serum IgG4 levels greater than the upper normal limit (105 mg/dL). Multivariate logistic regression analysis adjusted for age, gender, hypertension, dyslipidemia, diabetes, and coronary artery disease showed that neither elevated IgG4 (IgG4 > 105 mg/dL) nor elevated sIR-2R (sIL-2R > 519 U/mL) significantly predicted aortic aneurysm; the odds ratio was 1.21 (95% CI 0.53–2.72) for elevated IgG4 and 0.99 (95% CI 0.55–1.77) for elevated sIL-2R. Association remained non-significant even when the dependent variables were subdivided into abdominal and thoracic ones (data not shown). These data support the notion that the elevation of serum levels of IgG4 and sIL-2R in patients with coronary artery disease [13] may not have been attributed to the coexistence of coronary artery disease and aortic aneurysm in that study population. There are several possible explanations for why serum IgG4 levels were not higher in patients with aortic aneurysm than in those without. First, although several previous studies have shown a marked increase in serum IgG4 levels in patients with inflammatory aortic aneurysm, only one patient was diagnosed to have inflammatory aortic aneurysm in our series. Second, even in patients with abdominal aortic aneurysm of an inflammatory nature, which may account for 5–10% of all cases of abdominal aortic aneurysm [14], more than 40% of patients do not have increased serum IgG4 levels [15]. In addition, the prevalence of IgG4-related pathologies was observed in only about 4% of patients with thoracic aortic aneurysm/aortitis [16]. These findings collectively indicate that most patients with aortic aneurysm may not have elevated serum IgG4 levels. Third, serum IgG4 levels may be elevated in diseases other than inflammatory aortic aneurysm; these include coronary periarteritis [8] and retroperitoneal fibrosis, and other autoimmune disorders [3]. In conclusion, among patients who underwent coronary artery angiography, neither serum IgG4 nor sIL-2R levels were elevated in those with abdominal and/or thoracic aortic aneurysm. We suggest that the observed association between coronary artery disease and elevated serum levels of IgG4 and sIL-2R [13] may not be attributed to the relationship between aortic aneurysm and these biomarkers. Acknowledgments The work was supported in part by Health Sciences Research Grants of The Ministry of Health, Labour and Welfare of Japan (Research on Hepatitis, Acute Aortic Syndrome), Mitsui Life Social Welfare Foundation, and the Japan Society for the Promotion of Science (JSPS) through its “Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program).” References [1] Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 2001;344:732–8.
603
[2] Ishizaka N, Sakamoto A, Imai Y, Terasaki F, Nagai R. Multifocal fibrosclerosis and IgG4-related disease involving the cardiovascular system. J Cardiol; in press. [3] Sakamoto A, Nagai R, Saito K, et al. Idiopathic retroperitoneal fibrosis, inflammatory aortic aneurysm, and inflammatory pericarditis – retrospective analysis of 11 case histories. J Cardiol; in press. [4] Kasashima S, Zen Y, Kawashima A, et al. Inflammatory abdominal aortic aneurysm: close relationship to IgG4-related periaortitis. Am J Surg Pathol 2008;32:197–204. [5] Sakata N, Tashiro T, Uesugi N, et al. IgG4-positive plasma cells in inflammatory abdominal aortic aneurysm: the possibility of an aortic manifestation of IgG4related sclerosing disease. Am J Surg Pathol 2008;32:553–9. [6] Matsumoto Y, Kasashima S, Kawashima A, et al. A case of multiple immunoglobulin G4-related periarteritis: a tumorous lesion of the coronary artery and abdominal aortic aneurysm. Hum Pathol 2008;39:975–80. [7] Ikutomi M, Matsumura T, Iwata H, et al. Giant tumorous legions surrounding the right coronary artery associated with immunoglobulin-G4-related systemic disease. Cardiology 2011;120:22–6. [8] Tanigawa J, Daimon M, Murai M, et al. IgG4-related coronary periarteritis in patients presenting with myocardial ischemia. Hum Pathol; in press. [9] Olsson AG, Schwartz GG, Jonasson L, Linderfalk C. Are early clinical effects of cholesterol lowering mediated through effects on inflammation. Acta Physiol Scand 2002;176:147–50. [10] Wadwa RP, Kinney GL, Ogden L, et al. Soluble interleukin-2 receptor as a marker for progression of coronary artery calcification in type 1 diabetes. Int J Biochem Cell Biol 2006;38:996–1003. [11] Satoh D, Inami N, Shimazu T, et al. Soluble TRAIL prevents RANTES-dependent restenosis after percutaneous coronary intervention in patients with coronary artery disease. J Thromb Thrombolysis 2010;29:471–6. [12] Sato Y, Kojima M, Takata K, et al. Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman’s disease. Mod Pathol 2009;22:589–99. [13] Sakamoto A, Ishizaka N, Saito K, et al. Serum levels of IgG4 and soluble interleukin-2 receptor in patients with coronary artery disease. Clin Chim Acta 2012;413:577–81. [14] Hellmann DB, Grand DJ, Freischlag JA. Inflammatory abdominal aortic aneurysm. JAMA 2007;297:395–400. [15] Kasashima S, Zen Y, Kawashima A, et al. A new clinicopathological entity of IgG4-related inflammatory abdominal aortic aneurysm. J Vasc Surg 2009;49:1264–71, discussion 1271. [16] Kasashima S, Zen Y, Kawashima A, et al. A clinicopathologic study of immunoglobulin G4-related sclerosing disease of the thoracic aorta. J Vasc Surg 2010;52:1587–95.
Aiko Sakamoto ∗ Department of Cardiovascular Medicine, the University of Tokyo Graduate School of Medicine, Tokyo, Japan Nobukazu Ishizaka a,b Department of Cardiovascular Medicine, the University of Tokyo Graduate School of Medicine, Tokyo, Japan b Department of Cardiology, Osaka Medical College, Osaka, Japan a
Yasushi Imai Ryozo Nagai Department of Cardiovascular Medicine, the University of Tokyo Graduate School of Medicine, Tokyo, Japan ∗ Corresponding author at: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo, Tokyo, Japan. Tel.: +81 3 3815 5411; fax: +81 3 5800 8806. E-mail address: [email protected] (A. Sakamoto)
4 January 2012 Available online 4 February 2012
Contents lists available at SciVerse ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Letter to the Editor Serum levels of IgG4 and soluble interleukin-2 receptor in patients with abdominal and thoracic aortic aneurysm who undergo coronary angiography Keywords: IgG4-related systemic sclerosing disease Inflammation Aortic aneurysm Coronary artery disease Biomarkers
To the Editor Since Hamano et al. reported the infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in autoimmune pancreatitis [1], an IgG4-related clinicopathological condition is now recognized in a wide variety of organs including endocrine, urinary, and cardiovascular systems [2,3]. Inflammatory abdominal aortic aneurysm is a condition that shows dense periaortic fibrosis containing infiltrated inflammatory cells, and this relatively rare disorder is, albeit not always, IgG4-related [4]. It should be noted, however, that periaortic infiltration of IgG4-positive plasma cells may be observed in aortic aneurysm of an atherosclerotic [5], as well as an inflammatory nature. It has increasingly been recognized that IgG4-related perivascular immune inflammation can be observed not only in large vessels, such as aorta, but also in smaller-sized vessels such as coronary arteries [6–8]. In the current study, we measured serum levels of not only IgG4 but also soluble interleukin-2 receptor (sIL-2R), another marker of lymphocytic activation, which was because several previous studies suggested the association between sIL-2R and coronary artery disease [9–11]. In addition, a recent study showed that elevation of serum sIL-2R levels was observed in all patients (n = 9) with IgG4-related lymphadenopathy [12], although physiological relevance of elevation of sIL-2R in IgG4-related disease remains unclear. We have also recently shown that serum IgG4 and sIL2R levels were higher in patients with coronary artery stenosis among patients who were naïve for coronary artery interventions [13]. Intriguingly, the association between these biomarkers and coronary artery stenosis was in part independent of other atherosclerotic risk factors. In that study, however, 40 of the 286 patients enrolled were known to have aortic aneurysm; therefore, it might be questioned whether the observed relationship could be explained by the association between aortic aneurysm and IgG4. Here, after increasing the sample size, we set out to assess this point. The study was approved by The Ethical Committee of University of Tokyo, Tokyo, Japan. Written informed consent was obtained from all subjects. We enrolled 571 patients who underwent coronary angiography between 2005 and 2009, and, among them, 86 patients had aortic aneurysm (abdominal, 65, and thoracic, 37), of 0021-9150/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2012.01.038
which one was diagnosed as inflammatory aortic aneurysm with serum IgG4 levels of 115.0 mg/dL and sIL-2R levels of 592 U/mL. The exclusion criteria were acute myocardial infarction, and lack of informed consent for study enrollment. Unlike our preceding paper [13], patients who had a history of coronary interventions were not excluded from this study population (percutaneous coronary interventions 171; coronary artery bypass surgery 50). Serum levels of IgG4 were determined by turbidimetry and those of sIL2R were measured by enzyme-linked immunosorbent assay (SRL, Tokyo, Japan). A summary of the data of patients is provided in Table 1. The mean age was slightly, but significantly, higher, and male gender was more prevalent in patients with aortic aneurysm. The correlation coefficient between age and serum IgG4 was −0.044 (P = 0.302), and that between age and serum sIL-2R was 0.149 (P < 0.001) in this study population. Neither serum levels of IgG4 nor those of sIL-2R differed significantly between patients with and without aortic aneurysm. We then compared these biomarkers after subdividing patients according to the presence or absence of the coronary artery disease. Among 409 patients who had significant coronary artery disease, 51 patients had, and 358 patients did not have, aortic aneurysm. Serum levels of IgG4 (median 37.4 mg/dL, interquartile range [IR] 21.2–59.5) and sIL-2R (median 414 U/mL,
Table 1 Baseline characteristics of the study patients. Variables
AA group (n = 86)
no-AA group (n = 485)
Male gender, n (%) Age, years BMI, kg/m2 Systolic BP, mmHg Diastolic BP, mmHg The median of IgG4, mg/dL (IR) The median of sIL-2R, U/mL (IR) Old myocardial infarction, n (%) Congestive heart failure, n (%) Renal failure on hemodialysis, n (%) Hypertension, n (%) Dyslipidemia, n (%) Diabetes, n (%) Arteriosclerosis obliterans, n (%) Valvular heart disease, n (%) Smoking
72 (83.7) 69.3 ± 11.3 23.2 ± 3.7 127 ± 15 73 ± 11 36.6 (21.2–64.9) 384 (312–516) 11 (12.8) 8 (9.3) 1 (1.2)
352 (72.6) 66.4 ± 10.1 24.0 ± 3.5 131 ± 19 74 ± 13 32.5 (17.1–56.4) 374 (289–508) 106 21.9) 65 (13.4) 17 (3.5)
72 83.7) 36 (41.9) 15 (17.4) 5 (5.8)
408 (84.1) 328 (67.6) 226 (46.6) 35 (7.2)
4 (4.7)
39 (8.0)
Never, n (%)
22 (25.6)
172 (35.5)
Former, n (%)
47 (54.7)
230 (47.4)
Current, n (%)
17 (19.8)
83 (17.1)
P value 0.029 0.020 0.064 0.032 0.794 0.245 0.429 0.055 0.291 0.252 0.925 <0.001 <0.001 0.639 0.272 0.204
Values are presented as the mean ± standard deviation unless described otherwise. AA, BMI and BP indicate aortic aneurysm, body mass index and blood pressure, respectively. IR indicates interquartile range.
Letter to the Editor / Atherosclerosis 221 (2012) 602–603
IR 334–553) in patients with aortic aneurysm did not significantly differ from those in patients without aortic aneurysm (IgG4, median 34.1 mg/dL, IR 18.1–58.8, P = 0.602; sIL-2R, median 392 U/mL, IR 303–524, P = 0.176, by Mann–Whitney test). Among 162 patients who did not have significant coronary artery disease, 35 patients had, and 127 patients did not have, aortic aneurysm. Serum levels of IgG4 (median 33.7 mg/dL, IR 18.1–68.4) and sIL-2R (median 356 U/mL, IR 274–422) in patients with aortic aneurysm, again, did not significantly differ from those in patients without aortic aneurysm (IgG4, median 28.5 mg/dL, IR 14.9–45.7, P = 0.112; sIL2R, median 317 U/mL, IR 260–450, P = 0.460). It was found that 42 patients (8.7%) in the non-aneurysm group and 9 patients (10.5%) in the aneurysm group had serum IgG4 levels greater than the upper normal limit (105 mg/dL). Multivariate logistic regression analysis adjusted for age, gender, hypertension, dyslipidemia, diabetes, and coronary artery disease showed that neither elevated IgG4 (IgG4 > 105 mg/dL) nor elevated sIR-2R (sIL-2R > 519 U/mL) significantly predicted aortic aneurysm; the odds ratio was 1.21 (95% CI 0.53–2.72) for elevated IgG4 and 0.99 (95% CI 0.55–1.77) for elevated sIL-2R. Association remained non-significant even when the dependent variables were subdivided into abdominal and thoracic ones (data not shown). These data support the notion that the elevation of serum levels of IgG4 and sIL-2R in patients with coronary artery disease [13] may not have been attributed to the coexistence of coronary artery disease and aortic aneurysm in that study population. There are several possible explanations for why serum IgG4 levels were not higher in patients with aortic aneurysm than in those without. First, although several previous studies have shown a marked increase in serum IgG4 levels in patients with inflammatory aortic aneurysm, only one patient was diagnosed to have inflammatory aortic aneurysm in our series. Second, even in patients with abdominal aortic aneurysm of an inflammatory nature, which may account for 5–10% of all cases of abdominal aortic aneurysm [14], more than 40% of patients do not have increased serum IgG4 levels [15]. In addition, the prevalence of IgG4-related pathologies was observed in only about 4% of patients with thoracic aortic aneurysm/aortitis [16]. These findings collectively indicate that most patients with aortic aneurysm may not have elevated serum IgG4 levels. Third, serum IgG4 levels may be elevated in diseases other than inflammatory aortic aneurysm; these include coronary periarteritis [8] and retroperitoneal fibrosis, and other autoimmune disorders [3]. In conclusion, among patients who underwent coronary artery angiography, neither serum IgG4 nor sIL-2R levels were elevated in those with abdominal and/or thoracic aortic aneurysm. We suggest that the observed association between coronary artery disease and elevated serum levels of IgG4 and sIL-2R [13] may not be attributed to the relationship between aortic aneurysm and these biomarkers. Acknowledgments The work was supported in part by Health Sciences Research Grants of The Ministry of Health, Labour and Welfare of Japan (Research on Hepatitis, Acute Aortic Syndrome), Mitsui Life Social Welfare Foundation, and the Japan Society for the Promotion of Science (JSPS) through its “Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program).” References [1] Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 2001;344:732–8.
603
[2] Ishizaka N, Sakamoto A, Imai Y, Terasaki F, Nagai R. Multifocal fibrosclerosis and IgG4-related disease involving the cardiovascular system. J Cardiol; in press. [3] Sakamoto A, Nagai R, Saito K, et al. Idiopathic retroperitoneal fibrosis, inflammatory aortic aneurysm, and inflammatory pericarditis – retrospective analysis of 11 case histories. J Cardiol; in press. [4] Kasashima S, Zen Y, Kawashima A, et al. Inflammatory abdominal aortic aneurysm: close relationship to IgG4-related periaortitis. Am J Surg Pathol 2008;32:197–204. [5] Sakata N, Tashiro T, Uesugi N, et al. IgG4-positive plasma cells in inflammatory abdominal aortic aneurysm: the possibility of an aortic manifestation of IgG4related sclerosing disease. Am J Surg Pathol 2008;32:553–9. [6] Matsumoto Y, Kasashima S, Kawashima A, et al. A case of multiple immunoglobulin G4-related periarteritis: a tumorous lesion of the coronary artery and abdominal aortic aneurysm. Hum Pathol 2008;39:975–80. [7] Ikutomi M, Matsumura T, Iwata H, et al. Giant tumorous legions surrounding the right coronary artery associated with immunoglobulin-G4-related systemic disease. Cardiology 2011;120:22–6. [8] Tanigawa J, Daimon M, Murai M, et al. IgG4-related coronary periarteritis in patients presenting with myocardial ischemia. Hum Pathol; in press. [9] Olsson AG, Schwartz GG, Jonasson L, Linderfalk C. Are early clinical effects of cholesterol lowering mediated through effects on inflammation. Acta Physiol Scand 2002;176:147–50. [10] Wadwa RP, Kinney GL, Ogden L, et al. Soluble interleukin-2 receptor as a marker for progression of coronary artery calcification in type 1 diabetes. Int J Biochem Cell Biol 2006;38:996–1003. [11] Satoh D, Inami N, Shimazu T, et al. Soluble TRAIL prevents RANTES-dependent restenosis after percutaneous coronary intervention in patients with coronary artery disease. J Thromb Thrombolysis 2010;29:471–6. [12] Sato Y, Kojima M, Takata K, et al. Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman’s disease. Mod Pathol 2009;22:589–99. [13] Sakamoto A, Ishizaka N, Saito K, et al. Serum levels of IgG4 and soluble interleukin-2 receptor in patients with coronary artery disease. Clin Chim Acta 2012;413:577–81. [14] Hellmann DB, Grand DJ, Freischlag JA. Inflammatory abdominal aortic aneurysm. JAMA 2007;297:395–400. [15] Kasashima S, Zen Y, Kawashima A, et al. A new clinicopathological entity of IgG4-related inflammatory abdominal aortic aneurysm. J Vasc Surg 2009;49:1264–71, discussion 1271. [16] Kasashima S, Zen Y, Kawashima A, et al. A clinicopathologic study of immunoglobulin G4-related sclerosing disease of the thoracic aorta. J Vasc Surg 2010;52:1587–95.
Aiko Sakamoto ∗ Department of Cardiovascular Medicine, the University of Tokyo Graduate School of Medicine, Tokyo, Japan Nobukazu Ishizaka a,b Department of Cardiovascular Medicine, the University of Tokyo Graduate School of Medicine, Tokyo, Japan b Department of Cardiology, Osaka Medical College, Osaka, Japan a
Yasushi Imai Ryozo Nagai Department of Cardiovascular Medicine, the University of Tokyo Graduate School of Medicine, Tokyo, Japan ∗ Corresponding author at: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo, Tokyo, Japan. Tel.: +81 3 3815 5411; fax: +81 3 5800 8806. E-mail address: [email protected] (A. Sakamoto)
4 January 2012 Available online 4 February 2012