IgG4-positive cell infiltration in various cardiovascular disorders - results from histopathological analysis of surgical samples

Abstract

BackgroundThe diagnosis of Immunoglobulin G4 (IgG4)-related disease (IgG4-RD), in general, depends on serum IgG4 concentrations and histopathological findings; therefore, diagnosis of IgG4-RD in cardiovascular organs/tissues is often difficult owing to the risk of tissue sampling.MethodsPrevalence of IgG4-positive lymphoplasmacytic infiltration in 103 consecutive cardiovascular surgical samples from 98 patients with various cardiovascular diseases was analyzed immunohistochemically.ResultsThe diagnoses of the enrolled patients included aortic aneurysm (abdominal, n = 8; thoracic, n = 9); aortic dissection (n = 20); aortic stenosis (n = 24), aortic regurgitation (n = 10), and mitral stenosis/regurgitation (n = 17). In total, 10 (9.7%) of the 103 specimens showed IgG4-positive cell infiltration with various intensities; five of these were aortic valve specimens from aortic stenosis, and IgG4-positive cell infiltration was present at >10 /HPF in three of them. In one aortic wall sample from an abdominal aortic aneurysm, various histopathological features of IgG4-RD, such as IgG4-positive cell infiltration, obliterating phlebitis, and storiform fibrosis, were observed.ConclusionsIgG4-positive cell infiltration was observed in 9.7% of the surgical cardiovascular specimens, mainly in the aortic valve from aortic stenosis and in the aortic wall from aortic aneurysm. Whether IgG4-positive cell infiltration has pathophysiological importance in the development or progression of cardiovascular diseases should be investigated in future studies.

IgG4-related disease of the mitral valve demonstrated by immunohistochemistry

“…A review of the literature described two cases of IgG4-RD involving the aortic valve requiring valve replacement 5. The challenge in obtaining a tissue diagnosis for IgG4-RD involving the cardiovascular system is the risk of the procedure, leading some to question whether IgG4-RD valvulopathies are underdiagnosed 6. Furthermore, the subsequent finding of a concomitant malignancy in our patient reflects prior observations showing the association of IgG4-RD and cancer.…”

IgG4-Positive Plasmacytic Infiltration in Aortic Wall and Aortic Valve Surgical Samples and Its Relation to Preoperative Serum IgG4 Levels

“…Specimens: In our previous study examining histological samples obtained during cardiothoracic surgery over a 1year period, IgG4-positive cell infiltration was observed only in aortic wall and aortic valve samples. 7) In this study, therefore, histological analysis of either the aortic valve or aortic wall was carried out on 282 consecutive histological specimens (143 aortic wall, 139 aortic valve) obtained from 275 patients who underwent cardiovascular surgery at the Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, between August 2012…”

“…The samples analyzed in the current study included those analyzed in our previous study, corresponding to patients who underwent cardiothoracic surgery between January 2014 and December 2014. 7) Histopathological analysis: Histological evaluation was carried out on formalin-fixed and paraffin-embedded specimens. Immunostaining was performed using antibody against IgG4 and CD138, as described elsewhere.…”

“…Immunostaining was performed using antibody against IgG4 and CD138, as described elsewhere. 7) IgG4positive cell infiltration was graded as follows: negative, 10/higher power fields (hpf), 1-10/hpf, 11-30/hpf, 31-60/ hpf, 61-100/hpf, and > 100/hpf, and ratio of IgG4/ CDC138 was calculated when > 10/hpf IgG4-positive cell infiltration was observed. Measurement of serum IgG4 level: Serum samples were available in 48 patients (50 samples) who had been admitted to the department of cardiology for preoperative evaluation or other purposes before their admission to the department of the cardiothoracic surgery.…”

“…We previously demonstrated in a preliminary study that tissue infiltration of IgG4-positive cell may be observed with the frequency of more than 10% in surgically resected samples of the aortic wall and aortic valve. 7,8) The aim of the current study is to reassess IgG4-positive cell infiltration in aortic wall and aortic valve samples by a larger sample size and to examine whether preoperative serum IgG4 levels, when available, were associated with IgG4-positive cell infiltration in these tissues.…”