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Clinical features and predictive value of serum inflammatory markers of perivascular involvement in immunoglobulin G4-related disease

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Abstract

Vascular and/or perivascular involvements of sclerotic inflammation (perivasculitis) are a complication of immunoglobulin G4-related disease (IgG4-RD). We sought to examine clinical manifestations of perivasculitis by computed tomography (CT) in patients with elevated serum IgG4 levels, and then to evaluate some potential predictors of perivasculitis in definite IgG4-RD patients. From a database of patients with serum IgG4 measurements, we selected 81 patients with elevated serum IgG4 levels (≥135 mg/dl). Perivasculitis was defined radiologically as thickened contrast-enhanced rind surrounding the aorta and its major artery on CT imaging. We found 15 patients with perivasculitis; 10 patients in the definite (n = 37), four in the possible (n = 18), and one in the excluded (n = 26) IgG4-RD groups. Clinical predictors of perivasculitis were investigated in 34 untreated patients with definite IgG4-RD. Patients with perivasculitis (n = 10) had significantly higher age at diagnosis (74.2 ± 8.8 vs 63.5 ± 9.9 years, P = 0.006), higher levels of serum IgG4 (754 vs 292 mg/dl, P = 0.007) and C-reactive protein (CRP, 0.52 mg/dl vs 0.10 mg/dl, P = 0.001) than patients without perivasculitis (n = 24). The sensitivity and specificity of serum CRP ≥0.25 mg/dl for identifying perivasculitis in the definite IgG4-RD group were 100 and 71%, respectively (area under the receiver operating characteristic curve 0.863). Our results indicate that IgG4-related perivasculitis was associated with elevated levels of serum CRP and older age, and that CRP may be a useful marker for detecting perivascular involvement in IgG4-RD.

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References

  1. Stone JH, Zen Y, Deshpande V (2012) IgG4-related disease. N Engl J Med 366:539–551

    Article  CAS  PubMed  Google Scholar 

  2. Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, Fukushima M, Nikaido T, Nakayama K, Usuda N, Kiyosawa K (2001) High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 344:732–738

    Article  CAS  PubMed  Google Scholar 

  3. Kamisawa T, Funata N, Hayashi Y, Eishi Y, Koike M, Tsuruta K, Okamoto A, Egawa N, Nakajima H (2003) A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol 38:982–984

    Article  CAS  PubMed  Google Scholar 

  4. Stone JH, Khosroshahi A, Hilgenberg A, Spooner A, Isselbacher EM, Stone JR (2009) IgG4-related systemic disease and lymphoplasmacytic aortitis. Arthritis Rheum 60:3139–3145

    Article  PubMed  Google Scholar 

  5. Urabe Y, Fujii T, Kurushima S, Tsujiyama S, Kihara Y (2012) Pigs-in-a-blanket coronary arteries: a case of immunoglobulin G4-related coronary periarteritis assessed by computed tomography coronary angiography, intravascular ultrasound, and positron emission tomography. Circ Cardiovasc Imaging 5:685–687

    Article  PubMed  Google Scholar 

  6. Kusunose K, Hotchi J, Takagawa Y, Nishio S, Ise T, Tobiume T, Yamaguchi K, Yagi S, Iwase T, Yamada H, Soeki T, Wakatsuki T, Sata M (2015) Serial imaging changes during treatment of immunoglobulin G4-related disease with multiple pseudotumors. Circulation 131:1882–1883

    Article  PubMed  Google Scholar 

  7. Qian Q, Kashani KB, Miller DV (2009) Ruptured abdominal aortic aneurysm related to IgG4 periaortitis. N Engl J Med 361:1121–1123

    Article  CAS  PubMed  Google Scholar 

  8. Castelein T, Coudyzer W, Blockmans D (2015) IgG4-related periaortitis vs idiopathic periaortitis: is there a role for atherosclerotic plaque in the pathogenesis of IgG4-related periaortitis? Rheumatology 54:1250–1256

    Article  PubMed  Google Scholar 

  9. Hourai R, Miyamura M, Tasaki R, Iwata A, Takeda Y, Morita H, Hanaoka N, Tanigawa J, Shibata K, Takeshita A, Kawano M, Sato Y, Hirose Y, Ishizaka N (2016) A case of IgG4-related lymphadenopathy, pericarditis, coronary artery periarteritis and luminal stenosis. Heart Vessels 31:1709–1713

    Article  PubMed  Google Scholar 

  10. Stone JH, Khosroshahi A, Deshpande V, Chan JK, Heathcote JG, Aalberse R, Azumi A, Bloch DB, Brugge WR, Carruthers MN, Cheuk W, Cornell L, Castillo CF, Ferry JA, Forcione D, Klöppel G, Hamilos DL, Kamisawa T, Kasashima S, Kawa S, Kawano M, Masaki Y, Notohara K, Okazaki K, Ryu JK, Saeki T, Sahani D, Sato Y, Smyrk T, Stone JR, Takahira M, Umehara H, Webster G, Yamamoto M, Yi E, Yoshino T, Zamboni G, Zen Y, Chari S (2012) Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum 64:3061–3067

    Article  CAS  PubMed  Google Scholar 

  11. Inoue D, Zen Y, Abo H, Gabata T, Demachi H, Yoshikawa J, Miyayama S, Nakanuma Y, Matsui O (2011) Immunoglobulin G4-related periaortitis and periarteritis: CT findings in 17 patients. Radiology 261:625–633

    Article  PubMed  Google Scholar 

  12. Perugino CA, Wallace ZS, Meyersohn N, Oliveira G, Stone JR, Stone JH (2016) Large vessel involvement by IgG4-related disease. Medicine (Baltimore) 95:e3344

    Article  CAS  Google Scholar 

  13. Mitchinson MJ (1970) The pathology of idiopathic retroperitoneal fibrosis. J Clin Pathol 23:681–689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Parums DV, Mitchinson MJ (1981) Demonstration of immunoglobulin in the neighbourhood of advanced atherosclerotic plaques. Atherosclerosis 38:211–216

    Article  CAS  PubMed  Google Scholar 

  15. Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, Matsui S, Yoshino T, Nakamura S, Kawa S, Hamano H, Kamisawa T, Shimosegawa T, Shimatsu A, Nakamura S, Ito T, Notohara K, Sumida T, Tanaka Y, Mimori T, Chiba T, Mishima M, Hibi T, Tsubouchi H, Inui K, Ohara H (2012) Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol 22:21–30

    Article  CAS  PubMed  Google Scholar 

  16. Tsushima H, Yamamoto H, Kitagawa T, Urabe Y, Tatsugami F, Awai K, Kihara Y (2015) Association of epicardial and abdominal visceral adipose tissue with coronary atherosclerosis in patients with a coronary artery calcium score of zero. Circ J 79:1084–1091

    Article  PubMed  Google Scholar 

  17. Mizushima I, Inoue D, Yamamoto M, Yamada K, Saeki T, Ubara Y, Matsui S, Masaki Y, Wada T, Kasashima S, Harada K, Takahashi H, Notohara K, Nakanuma Y, Umehara H, Yamagishi M, Kawano M (2014) Clinical course after corticosteroid therapy in IgG4-related aortitis/periaortitis and periarteritis: a retrospective multicenter study. Arthritis Res Ther 16:R156

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kasashima S, Zen Y, Kawashima A, Konishi K, Sasaki H, Endo M, Matsumoto Y, Kawakami K, Kasashima F, Moriya M, Kimura K, Ohtake H, Nakanuma Y (2008) Inflammatory abdominal aortic aneurysm: close relationship to IgG4-related periaortitis. Am J Surg Pathol 32:197–204

    Article  PubMed  Google Scholar 

  19. Henderson EL, Geng YJ, Sukhova GK, Whittemore AD, Knox J, Libby P (1999) Death of smooth muscle cells and expression of mediators of apoptosis by T lymphocytes in human abdominal aortic aneurysms. Circulation 99:96–104

    Article  CAS  PubMed  Google Scholar 

  20. Ridker PM (2001) High-sensitivity C-reactive protein potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 103:1813–1818

    Article  CAS  PubMed  Google Scholar 

  21. Nakagawa M, Shimada K, Yoshiyama M (2016) New insights into spotty calcification and plaque rupture in acute coronary syndrome: an optical coherence tomography study. Heart Vessels 31:1915–1922

    Article  PubMed  Google Scholar 

  22. Ebe H, Tsuboi H, Hagiya C, Takahashi H, Yokosawa M, Hagiwara S, Hirota T, Kurashima Y, Takai C, Miki H, Asashima H, Umeda N, Kondo Y, Ogishima H, Suzuki T, Chino Y, Matsumoto I, Sumida T (2015) Clinical features of patients with IgG4-related disease complicated with perivascular lesions. Mod Rheumatol 25:105–109

    Article  CAS  PubMed  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Hideya Yamamoto, Toshiro Kitagawa, Atsushi Senoo, Yumiko Kubo Nakamoto & Yasuki Kihara

  2. Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan

    Eiji Sugiyama

  3. Department of Gastroenterology and Metabolism, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

    Masahiro Serikawa & Kazuaki Chayama

  4. Department of Diagnostic Radiology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

    Fuminari Tatsugami & Kazuo Awai

  5. Clinical Laboratory, Hiroshima University Hospital, Hiroshima, Japan

    Michiya Yokozaki

Authors
  1. Hideya Yamamoto
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  2. Eiji Sugiyama
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  3. Masahiro Serikawa
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  4. Fuminari Tatsugami
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  8. Yumiko Kubo Nakamoto
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  9. Kazuo Awai
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  10. Kazuaki Chayama
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  11. Yasuki Kihara
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Correspondence to Hideya Yamamoto.

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Funding

Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Tokyo, Japan, No. 26461111).

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None of the authors has a conflict of interest to declare.

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Yamamoto, H., Sugiyama, E., Serikawa, M. et al. Clinical features and predictive value of serum inflammatory markers of perivascular involvement in immunoglobulin G4-related disease. Heart Vessels 32, 1176–1185 (2017). https://doi.org/10.1007/s00380-017-0987-2

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  • DOI: https://doi.org/10.1007/s00380-017-0987-2

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