Granulomatosis with Polyangiitis

Granulomatosis with Polyangiitis

Characteristics of Granulomatosis with Polyangiitis (GPA)

GPA is a systemic inflammatory disease. The kidneys and the upper and lower respiratory are all influenced by it. It is a relatively uncommon condition. Patients' serum presents anti-neutrophil cytoplasmic antibodies (ANCA) and they have necrotizing granulomatous vasculitis of small- and medium-sized vessels. GPA remains one of the most challenging diagnostic dilemmas in clinical medicine. From common respiratory and neurological symptoms to infrequent cardiac complications, this fatal systemic illness is difficult to distinguish from infectious etiologies and is often mistaken for an isolated complaint. The consequential delay in the necessary diagnosis and treatment can lead to a long-term disability or mortality due to the common rapid progression of the disease.

Clinical Manifestations of GPA

The majority of patients have symptoms in the ear, nose, and throat, such as crusting rhinorrhea, sinusitis, chronic otitis media, or damage of the facial cartilage with deformities causing saddle nose, and perforation of the nasal septum, the palate, or the pinna of the ear. Nasal-sinus involvement is the most common manifestation of GPA, the most common hallmark of the disease, and maybe the only sign in the localized forms. Nasal obstruction with hyposmia or anosmia is often the first symptom. Lung involvement affects 50 to 90% of patients. It is characterized by alveolar hemorrhage of variable severity and parenchymatous nodules. The most typical renal involvement is focal segmental necrotizing glomerulonephritis associated with extra capillary proliferation with pauci-immune crescent formation. The involvement of the peripheral nervous system affects about one-third of patients. It is characterized by mono neuritis multiplex or, less commonly, by sensorimotor neuropathy. Mucocutaneous lesions, mainly vascular purpura to the lower limbs, are reported in 10 to 50% of cases; they can be ulcerating, necrotic, and widespread. Ocular involvement occurs fairly frequently (14 to 60%), usually in the form of necrotizing nodular episcleritis. Scleritis, corneal ulcerations, and retinal vasculitis also occur.

The main clinical manifestations of GPA.Fig.1 The main clinical manifestations of GPA. (Guzman-Soto, et al., 2021)

Epidemiology of GPA

The overall annual incidence of GPA is approximately 2.4-11.3 cases per one million with no significant gender predilection. The age of symptom onset has a wide distribution, with a peak incidence between the ages of 41 and 68 years, and a very rare occurrence in childhood and young adults. There is a significantly higher prevalence of GPA amongst Caucasians, especially those from Northern Europe, compared to Asian and African populations. These differences may be attributed to differences in geographical, environmental, and genetic factors.

Etiology and Pathogenesis of GPA

GPA's complex multifactorial etiology is indicated to result from immunologic and environmental contributions in genetically predisposed individuals. Genetic predisposition amongst GPA patients is heterogeneous and may result in variations in Human leukocyte antigen-mediated antigen presentation, defective immune regulation, and an abnormal structure and function of the target antigen.

Monitoring lgG Sialylation Level as a Biomarker of GPA

Since glycosylated autoantibodies (AAbs) seem to be involved in autoimmune disease pathophysiology, they have been suggested to represent biomarkers for disease activity. Indeed, anti-neutrophil cytoplasm antibodies (ANCA) are pathogenic in GPA and their serum levels appear to be correlated with disease activity. However, this correlation is not close enough to reliably predict clinical outcomes and subsequent relapses. The Sialylation levels of IgGs from proteinase 3 (PR3)-ANCA contribute to the disease activity by modulating the intensity of ANCA-induced oxidative burst of neutrophils. Spectrometric analysis of IgG revealed a reduced level of 2,6 sialylated N-Glycans and a high level of galactosylated IgG among high activity scores of GPA patients. Moreover, we found that the sialylation levels of PR3-ANCA are lower in GPA patients with active vasculitis and determine the activity of GPA more closely than PR3-ANCA levels. Thus, we showed that the sialylation level of PR3-ANCA could be considered a more accurate biomarker of clinical activity in GPA than the PR3-ANCA serum level. These promising results remain to be further confirmed in larger series. As Glycosylation abnormalities have been described in a large number of autoimmune diseases, AAb glycosylation level assessment could become a new way to monitor disease activity and a new biomarker of clinical activity of autoimmune diseases, more accurate than AAb level alone.

Treatment of GPA

GPA is a serious disease, with a nearly always fatal outcome in the absence of treatment. Fortunately, with therapeutic approaches that are increasingly standardized and the emergence of new biotherapies, 90% of patients go into remission. Effective induction therapy with corticosteroids combined with cyclophosphamide or rituximab transformed the survival of patients with GPA, with 5-year survival rates > 80%.

Sialylation is a biomarker of GPA activity. Sialic acid also plays a key role in pathology and physiology. CD BioGlyco provides professional solutions for the Analysis of Sialic Acids. Our team is made up of individuals with many years of experience in this field. If you are interested in our services, please contact us for more detailed information.


  1. Guzman-Soto, M.I.; et al. From head to toe: granulomatosis with polyangiitis. RadioGraphics. 2021, 41(7): 1973-1991.
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