Background Recently, a new disease entity was established as IgG4-related aortitis/periaortitis and periarteritis including IgG4-related inflammatory abdominal aortic aneurysm (IgG4-IAAA) , while non-IgG4-IAAA was also recognized as a similar but immunohistochemically different disease entity . 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 , 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.
Stone JH et al. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum 2012;64:3061-7.
Kasashima S et al. IgG4-related inflammatory abdominal aortic aneurysm. Curr Opin Rheumatol. 2011;23:18-23.
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
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