An overview of the diagnosis and management of immunoglobulin G4–related disease

Abstract

What pathophysiologic mechanisms are involved in IgG4-related disease? The pathophysiology of IgG4-related disease is uncertain. Both genetic predisposition and environmental triggers may prompt aberrant immune pathways to perpetuate the disease. 15 An overview of current understanding of the disease is shown in Figure 1. 15-23 The pathology seems to be primarily affected by B cells. Patients with IgG4-related disease carry dominantly expanded clones of tissue B cells that produce immunoglobulins with greater antigen affinity and, preferentially, make more IgG4. However, the pathogenic role of IgG4 remains a contentious issue in view of its immune-modulating properties. 15,24 Expansion of regulatory T cells is observed, 22 which may contribute to fibrosis. Furthermore, a modified type 2 T-helper (Th2) cellular response 25 augments B-cell changes. 26,27 Maturation of B cells may also be directly stimulated by microbial components. 28 An overview of the diagnosis and management of immunoglobulin G4-related disease

Blocking IL-17: A Promising Strategy in the Treatment of Systemic Rheumatic Diseases

“…IgG4-related disease (IgG4-RD) is characterized by an increase in IgG4 + cells and circulating IgG4, which is associated with the development of a fibro-inflammatory process mediated by tissue infiltrations of immune cells, including IgG4-positive plasma cells. This process leads to the formation of pseudotumor structures that produce dysfunction or lesions in the affected organs [ 116 , 117 ]. Despite the mechanisms of action involved in this disease remaining largely unknown [ 118 ], some studies have suggested that IL-17 might be implicated in the pathogenesis of the disease.…”

A Challenging Diagnosis of IgG4-Related Disease When Understanding Limitations of Laboratory Testing Was Pivotal

“…However, as IgG4-RD can be patchy, renal biopsies can on occasion reveal normal histology [ 5 ]. Although no tissue from his aortic aneurysm repair was sent for pathology, his CT chest showed periaortic wall thickening as can be seen in IgG4-related aortitis [ 2 ].…”

“…Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated multisystem disease that is characterized by inflammation and fibrosis of affected organs [ 1 , 2 ]. Since the disease often presents with nonspecific symptoms and signs and can affect any organ or system, the diagnosis is challenging and often delayed.…”

Perirenal soft tissue infiltration from immunoglobulin G4–related disease

“…The definite diagnosis can be made based on imaging, serology (serum IgG4 > 1.35 g/L) and histology (IgG4+ plasma cells > 10/HPF or IgG4:IgG > 40%). 1 IgG4-related kidney disease usually presents as bilateral multiple renal nodules. 2 The presentation of perirenal soft tissue infiltration is uncommon, but should provoke further histopathologic work-up.…”

“…Even though there is no conclusive treatment, international consensus suggests giving induction therapy (prednisolone 40 mg/d) with tapering and aiming to stop treatment in three to six months. 1 If treated inadequately, IgG4related disease may cause renal dysfunction and progress to irreversible renal damage. 3…”