Is Granulomatosis with Polyangiitis (GPA) an autoimmune disease?

From the Guidelines

Yes, granulomatosis with polyangiitis (GPA) is an autoimmune disease. It is a type of vasculitis where the body's immune system mistakenly attacks its own blood vessels, particularly affecting small and medium-sized vessels in the lungs, kidneys, and upper respiratory tract. The condition is characterized by inflammation and granuloma formation that can damage organ systems.

Key Characteristics of GPA

• The autoimmune nature of GPA is evidenced by the presence of anti-neutrophil cytoplasmic antibodies (ANCA), particularly those targeting proteinase 3 (PR3-ANCA), in about 80-90% of patients 1.
• These antibodies activate neutrophils, leading to vessel damage and inflammation.
• Treatment typically involves immunosuppressive medications such as cyclophosphamide or rituximab for induction therapy, often combined with high-dose corticosteroids like prednisone (initially 1 mg/kg/day, maximum 80 mg daily) 1.

Treatment and Management

• Maintenance therapy may include azathioprine, methotrexate, or rituximab for 12-24 months or longer.
• Regular monitoring of organ function, ANCA levels, and medication side effects is essential for managing this chronic condition.
• The 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of ANCA-associated vasculitis recommends a reduced-dose glucocorticoid regimen over a standard-dose regimen for remission induction in patients with active, severe GPA/MPA 1.
• The guideline also suggests that either IV pulse glucocorticoids or high-dose oral glucocorticoids may be prescribed as part of initial therapy for patients with active, severe GPA/MPA.

From the FDA Drug Label

Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA) in adult and pediatric patients 2 years of age and older in combination with glucocorticoids A total of 197 patients with active, severe GPA and MPA (two forms of ANCA Associated Vasculitides) were treated in a randomized, double-blind, active-controlled, multicenter, non-inferiority study

Autoimmune Nature of Granulomatosis with Polyangiitis: The FDA drug label for rituximab indicates that Granulomatosis with Polyangiitis (GPA) is associated with ANCA (Anti-Neutrophil Cytoplasmic Antibodies), which suggests an autoimmune component.

• Key Points:
  • GPA is a form of ANCA Associated Vasculitis
  • Rituximab, a treatment for GPA, targets CD20-positive B cells, which are involved in the autoimmune response
  • The presence of ANCA in GPA patients supports the autoimmune nature of the disease 2, 2

From the Research

Definition and Classification of Granulomatis with Polyangitis

• Granulomatosis with polyangiitis (GPA) is an autoimmune small vessel vasculitis highly associated with anti-neutrophil cytoplasmic antibodies (ANCA) 3.
• The hallmarks of this condition are systemic necrotising vasculitis, necrotising granulomatous inflammation, and necrotising glomerulonephritis 3.
• GPA is diagnosed based on clinical manifestations of systemic vasculitis and histological evidence of necrotising vasculitis or granulomatous inflammation 3.

Pathogenesis and Genetics

• The aetiology of granulomatosis with polyangiitis is linked to environmental and infectious triggers inciting onset of disease in genetically predisposed individuals 3.
• Anti-neutrophil cytoplasmic antibodies are pathogenic and play an important role in the pathogenesis of this disease, although ANCA positivity is not essential for a clinical diagnosis of granulomatosis with polyangiitis 3.
• GPA typically evolves into two phases: an initial phase characterized by ear, nose and throat (ENT) manifestations, and a severe generalized phase defined by the occurrence of rapidly progressive glomerulonephritis, pulmonary hemorrhage, and arthritis 4.
• Susceptibility genes and loci have been identified by candidate gene approaches, genome-wide association studies, and meta-analyses, as well as familial association studies, including CTLA4, PTPN22, COL11A2, SERPINA1, and the MHC class II gene cluster 4.

Treatment and Management

• Immunosuppression and adjuvant therapies have contributed to the improved prognosis of granulomatosis with polyangiitis over the past decades 3.
• Treatment strategies are tailored to the severity of the disease, based on published evidence of the efficacy and safety of the immunosuppressive drugs indicated to manage active vasculitis and maintain clinical remission 3.
• Rituximab was shown to be noninferior to cyclophosphamide for remission induction, and methotrexate was noninferior to cyclophosphamide for induction of remission in nonsevere disease 5.
• For maintenance of remission, methotrexate and azathioprine showed no difference in the risk of relapse, while rituximab was superior to a tapering azathioprine strategy in major relapse-free survival 5.
• Discontinuation or use of low doses of maintenance therapy is associated with a higher relapse rate 6.
• Intravenous immunoglobulins represent an alternative adjuvant therapy, with beneficial effects reported in patients suffering from granulomatosis with polyangiitis 7.