A Transient Increase in the Serum ANCAs in Patients with SARS-CoV-2 Infection: A Signal of Subclinical Vasculitis or an Epiphenomenon with No Clinical Manifestations? A Pilot Study.

A relationship is emerging between SARS-CoV-2 infections and ANCA-associated vasculitis (AAV) because: (i) the pulmonary involvement of COVID-19 may mimic that observed in patients with AAV; (ii) the two diseases may occur together; (iii) COVID-19 may trigger AAV. However, few cases of AAV have been identified so far in COVID-19 patients. To define the frequency of ANCA autoimmunity in patients with SARS-CoV-2 infection, we analyzed the serum ANCAs and the serum PR3 and MPO antigens by immunoassays in 124 adult patients with a diagnosis of SARS-CoV-2 infection (16 were asymptomatic and 108 were hospitalized) and 48 control subjects. The serum ANCAs were significantly higher in the hospitalized patients compared with either the controls or the asymptomatic patients and increased with the progression of the COVID-19 severity. After one week of hospitalization, the values were significantly lower. In contrast, no differences emerged among the controls, asymptomatic and hospitalized patients for the PR3 and MPO serum levels. None of the patients had clinical signs of AAV with the exception of a severe pulmonary involvement. Further studies are necessary to define whether the increase in the serum ANCAs might mask subclinical vasculitis in a percentage of patients with SARS-CoV-2 infection or it is an epiphenomenon of SARS-CoV-2 infection with no clinical manifestations.

ANCA-Associated Vasculitis Following Pfizer-BioNTech COVID-19 Vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread around the world. As of the end of June 2021, there were approximately 181 million confirmed cases and more than 3.9 million deaths across the globe. The colossal impact of coronavirus disease 2019 (COVID-19) is driving the biggest vaccination campaign in human history. All 3 vaccines authorized for emergency use by the US Food and Drug Administration (Pfizer-BioNTech, Moderna, and Janssen/Johnson & Johnson) have been thoroughly studied and found to be safe and effective in preventing severe COVID-19 cases. While short-term side effects of COVID-19 vaccine resemble those of other vaccines, long-term side effects remain unknown. Rare side effects continue to surface as millions of people receive COVID-19 vaccines around the world, as compared with the thousands enrolled in the clinical trials. We report a case of new-onset renal-limited ANCA-associated vasculitis (AAV) in a 78-year-old woman with previously normal kidney function after receiving the Pfizer-BioNTech COVID-19 vaccine. The patient developed acute kidney injury with proteinuria and microscopic hematuria with many dysmorphic red blood cells in the urine. Anti-myeloperoxidase antibody titer was elevated. Kidney biopsy showed pauci-immune crescentic necrotizing glomerulonephritis. Kidney function improved after treatment with steroids and rituximab. Our patient had normal routine laboratory testing before the vaccination. Although this case cannot demonstrate a causal relationship between COVID-19 vaccination and AAV, ongoing surveillance for similar complications would be prudent as worldwide vaccination efforts continue.

Impaired HVJ-stimulated Interferon producing capacity in MPO-ANCA-associated vasculitis with rapidly progressive glomerulonephritis lead to susceptibility to infection.

ANCA-associated RPGN leads to renal failure through systemic vasculitis and diffuse crescentic glomerulonephritis. MPO-ANCA-RPGN patients are highly susceptible to infections. Our aim in this study was to uncover reasons why these patients were susceptible to infections. We analyzed various aspects of type I interferon system including HVJ-stimulated IFN-α producing capacity and plasmacytoid dendritic cell (pDC) number in whole blood in MPO-ANCA-RPGN patients. Compared with healthy subjects, MPO-ANCA-RPGN patients showed impaired HVJ-stimulated IFN-α producing capacity and lower pDC number with or without glucocorticoid treatment. Immuno-histological staining of MPO-ANCA-RPGN kidney samples revealed a few but apparent pDC in T cell infiltrating regions even in patients with low pDC number in their peripheral blood. Patients' low HVJ-stimulated IFN-α producing capacity and pDC numbers persisted even after patients underwent several years of treatment. Former infection was determined using patients' serum BPI, Lamp-2 and Calprotectin, since they are reflective of a history of infection. These markers were higher in MPO-ANCA-RPGN patients than in healthy subjects. These results indicate that impaired HVJ-stimulated IFN-α production as well as dysfunction of the IFN system might have resulted from a previous bout of infection and can be partially implicated in patients' long-term susceptibility and vulnerability to infection.