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THU0382 Involvement of Macrophages and A Proliferation-Inducing Ligand (APRIL) in Igg4-Related Inflammatory Abdominal Aortic Aneurysm
  1. I. Mizushima1,2,
  2. S. Kasashima3,
  3. K. Yamada2,
  4. K. Harada4,
  5. Y. Nakanuma4,
  6. M. Yamagishi5,
  7. M. Kawano2
  1. 1Division of Nephrology and Rheumatology, Department of Internal Medicine, Ishikawa Prefectural Central Hospital
  2. 2Division of Rheumatology, Department of Internal Medicine, Kanazawa University Graduate School of Medicine
  3. 3Department of Pathology and Department of Clinical Laboratory, National Hospital Organization, Kanazawa Medical Center
  4. 4Department of Human Pathology, Kanazawa University Graduate School of Medicine
  5. 5Division of Cardiology, Department of Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan


Background Recently, a new disease entity was established as IgG4-related aortitis/periaortitis and periarteritis including IgG4-related inflammatory abdominal aortic aneurysm (IgG4-IAAA) [1], while non-IgG4-IAAA was also recognized as a similar but immunohistochemically different disease entity [2]. However, the pathophysiology that discriminates these two entities remains to be clarified. A proliferation-inducing ligand (APRIL) is a cytokine that promotes activation, proliferation, and survival of B lymphocytes and plasma cells. High serum APRIL level was reported in IgG4-related disease [3], but histological analysis of APRIL in IgG4-RD is lacking.

Objectives To evaluate the involvement of APRIL histopathologically in IgG4-IAAA and non-IgG4-IAAA.

Methods We evaluated 12 IAAA patients whose aortic lesions were obtained surgically. Five of them were diagnosed with IgG4-IAAA based on histological findings of numerous IgG4-positive plasma cells [>50/high-power field (hpf) and an IgG4/IgG-positive cell ratio >60%] in the surgical specimens, while the remaining 7 were diagnosed as non-IgG4-IAAA. Clinicopathological findings including immunostaining of anti-membrane type APRIL antibody (Stalk-1) and anti-soluble APRIL antibody (Aprily-8) were analyzed. Dual fluorescent immunostaining of various cell surface markers and Stalk-1 was also performed.

Results The patients were 10 men and 2 women with an average age of 69.3 years. Clinically, patients histologically diagnosed with IgG4-IAAA showed significantly higher serum IgG4 and IgE levels than those diagnosed with non-IgG4-IAAA. Histopathologically, patients with IgG4-IAAA showed a tendency of a high prevalence of obliterative phlebitis and a thicker adventitia compared with those with non-IgG4-IAAA. Although all specimens of 12 patients showed infiltration of Stalk-1-positive APRIL-producing cells, the number of infiltrating those cells was significantly higher in IgG4-IAAA than in non-IgG4-IAAA (128±48/hpf vs 58±33/hpf, P =0.019). In addition, the soluble APRIL stained with Aprily-8 was more marked in IgG4-IAAA compared with non-IgG4-IAAA. There was a significant positive correlation between the number of infiltrating IgG4-bearing plasma cells and that of APRIL-producing cells (P =0.013). Dual fluorescent immunostaining revealed that macrophages including M2 macrophages were the major cells producing APRIL, while T cells, B cells, and plasma cells did not produce APRIL.

Conclusions Our data implicate APRIL-producing macrophages in the affected lesions in the pathophysiology of local IgG4 production, which may help to discriminate between IgG4-IAAA and non-IgG4-IAAA.


  1. Stone JH et al. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum 2012;64:3061-7.

  2. Kasashima S et al. IgG4-related inflammatory abdominal aortic aneurysm. Curr Opin Rheumatol. 2011;23:18-23.

  3. Kiyama K et al. Serum BAFF and APRIL levels in patients with IgG4-related disease and their clinical significance. Arthritis Res Ther. 2012;14:R86.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.2803

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