Analysis of Serum IgG Subclasses in Churg-Strauss Syndrome -The Meaning of Elevated Serum Levels of IgG4

Abstract

Objective Mikulicz's disease (MD) is characterized by symmetrical and persistent enlargement of the lacrimal and salivary glands. Recently it has been categorized as an 'Ig (immunoglobulin) G4-related disease.' It presents with elevated serum levels of IgG4 and abundant infiltration of IgG4-bearing plasmacytes in involved organs. Allergic symptoms are often observed in patients with IgG4-related disease. On the other hand, allergic diseases are often complicated with Churg-Strauss syndrome (CSS). Here we focused on CSS and analyzed the relation of IgG4 in its pathogenesis. Materials and MethodsWe analyzed five patients (2 men and 3 women) with CSS and 51 patients (20 men and 31 women) with MD who presented at Sapporo Medical University Hospital since 2001. We measured the serum concentrations of IgG subclasses in the patients with MD and CSS, and evaluated renal specimens from CSS patients, staining them for anti-IgG4 antibody. Results We surprisingly found elevated serum levels of IgG4 not only in MD but also in CSS patients. The renal specimens in CSS patients revealed the infiltration of IgG4-positive plasmacytes. Conclusion IgG4-bearing plasmacytes may be involved in the pathogenesis of CSS, and it is possible that an allergic reaction plays an important role in the pathogenesis of IgG4-related disease.

Hepatitis Associated with Hypereosinophilia Suspected to be Caused by HES that Also Presented with the Pathological Features of IgG4-related Disease

“…Hypereosinophilia and an elevated IgE level induce IL-10 and transforming growth factor-β (TGF-β) secretion from immunosuppressive T-cells and increase the serum IgG4 concentration (22). Subsequently, serum IgG4 interferes with allergic reactions by competing with IgE in the immune response and binding to mast cells (4,21,(23)(24)(25)(26)(27)(28). Therefore, hypereosinophilia and an elevated IgG4 concentration are simultaneously observed in some cases.…”

“…Its histological characteristics include the presence of IgG4-positive plasma cell infiltration in the involved organs, obliterative phlebitis and storiform or swirling fibrosis (3). Some histological features of IgG4-RD resemble those of HES, and the findings of other eosinophilic diseases, such as eosinophilic granulomatosis with polyangitis (EGPA), coincide with the IgG4-RD diagnostic criteria (4). Therefore, making a careful differential diagnosis is required in cases of an elevated serum IgG4 concentration accompanied by hypereosinophilia.…”

Churg-Strauss Syndrome Concomitant with Chronic Symmetrical Dacryoadenitis Suggesting Mikulicz's Disease

“…No previous reports have described the serum complement levels of CSS in detail; however, no review has shown hypocomplementemia in CSS until now. The five cases of CSS described by Yamamoto et al also showed normal or high levels of CH50 (2). In patients with IgG4-RD, including those with MD, the serum levels of complement are frequently at low levels and reflect the disease activity (7).…”

“…A diagnosis of IgG4-RD is not straightforward, as some known pathological conditions meet the same criteria and may be diagnosed as IgG4-RD "in a wide sense." Yamamoto et al claimed that in order to diagnosis IgG4-RD "in a narrow sense," both swelling of the involved organs and a lack of systemic inflammation must be present (2). Because the definition of IgG4- RD has not yet been established, determining the correct criteria for diagnosing IgG4-RD is difficult.…”

Clinical outcomes and pathological characteristics of immunoglobulin G4-related ophthalmic disease versus orbital inflammatory pseudotumor

“…Thus, ANCA-related vasculitis may not only include nonspecific inflammatory lesions [16], but also have abundant IgG4-positive plasma cells [17].…”