Anti-neutrophil cytoplasmic antibodies (ANCA): Antigen interactions and downstream effects

Sundqvist, Martina; Gibson, Kristen M; Bowers, Sarah M.; Niemietz, Iwona; Brown, Kelly L.

doi:10.1002/jlb.3vmr0220-438rr

Cited by 7 publications

(6 citation statements)

References 124 publications

(198 reference statements)

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“…ANCAs are reactive against multiple antigens in the cytoplasmic and perinuclear regions in neutrophils and monocytes. The most prevalent ANCAs in ANCA‐associated vasculitis target myeloperoxidase and proteinase 3 and are strongly associated with small vessel vasculitis 28 . It is believed that, in genetically predisposed patients, the first neutrophil immune response may lead to antigen presentation and chronic immune dysregulation in small vessel vasculitis 28 .…”

Section: Discussionmentioning

confidence: 99%

“…28 It is believed that, in genetically predisposed patients, the first neutrophil immune response may lead to antigen presentation and chronic immune dysregulation in small vessel vasculitis. 28 However, the immunopathology of vasculitis is still unclear. Several models have suggested that T-lymphocytes may play a leading role in the loss of tolerance and development of autoimmunity.…”

Section: Accepted Articlementioning

confidence: 99%

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COVID‐19 and Immunological Dysregulation: Can Autoantibodies be Useful?

Pascolini

Vannini

Deleonardi

et al. 2021

Clinical Translational Sci

144

153

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Coronavirus disease 2019 (COVID-19) is often associated with interstitial pneumonia. However, there is insufficient knowledge on the presence of autoimmune serological markers in patients with COVID-19. We analyzed the presence and role of autoantibodies in patients with COVID-19-associated pneumonia. We prospectively studied 33 consecutive patients with COVID-19, 31 (94%) of whom had interstitial pneumonia, and 25 age-and sex-matched patients with fever and/or pneumonia with etiologies other than COVID-19 as the pathological control group. All patients were tested for the presence of antinuclear antibodies (ANAs), antiantiphospholipid antibodies (APLs), and anti-cytoplasmic neutrophil antibodies (ANCAs). Clinical, biochemical, and radiological parameters were also collected. Fifteen of 33 (45%) patients tested positive for at least one autoantibody, including 11 who tested positive for ANAs (33%), 8 who tested positive for anti-cardiolipin antibodies (IgG and/or IgM) (24%), and 3 who tested positive for anti-β2-glycoprotein antibodies (IgG and/or IgM) (9%). ANCA reactivity was not detected in any patient. Patients that tested positive for autoantibodies had a significantly more severe prognosis than other patients did: 6 of 15 (40%) patients with autoantibodies died due to COVID-19 complications during hospitalization, whereas only 1 of 18 (5.5%) patients who did not have autoantibodies died (p = 0.03). Patients with poor prognosis (death due to COVID-19 complications) had a significantly higher respiratory rate at admission (23 breaths per minute vs. 17 breaths per minute; p = 0.03) and a higher frequency of autoantibodies (86% vs. 27%; p = 0.008). In conclusion, autoantibodies are frequently detected in patients with COVID-19 possibly reflecting a pathogenetic role of immune dysregulation. However, given the small number of patients, the association of autoantibodies with an unfavorable prognosis requires further multicenter studies.

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Section: Discussionmentioning

confidence: 99%

Section: Accepted Articlementioning

confidence: 99%

COVID‐19 and Immunological Dysregulation: Can Autoantibodies be Useful?

Pascolini

Vannini

Deleonardi

et al. 2021

Clinical Translational Sci

144

153

View full text Add to dashboard Cite

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“…There are only a limited number of studies showing vasculitis associated autoantibodies in COVID-19 patients ( Gazzaruso et al, 2020 ; Sacchi et al, 2020 ; Vlachoyiannopoulos et al, 2020 ; Chang et al, 2021a ). In ANCA associated vasculitis, the most common ANCAs target MPO and PR3 which are closely related with small vessel vasculitis ( Sundqvist et al, 2020 ). Vasculitis associated MPO antibody was detected only in one patient.…”

Section: Discussionmentioning

confidence: 99%

Antinuclear antibodies (ANAs) detected by indirect immunofluorescence (IIF) method in acute COVID-19 infection; future roadmap for laboratory diagnosis

Peker

Şener

Aydoğmuş

2021

Journal of Immunological Methods

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“…Although MPO and PR3 released by neutrophils may associate with the endothelium and in this manner target the endothelium for ANCA-mediated damage, it is also possible that disease processes are the result of the indirect action of ANCA, or are independent of autoantibodies, as may be the case in patients with ANCA-negative vasculitis (2).…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies Against Lysosome Associated Membrane Protein-2 (LAMP-2) in Pediatric Chronic Primary Systemic Vasculitis

et al. 2021

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BackgroundAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis in adults and children that commonly affects the kidneys. Although the frequent antigenic, and presumed pathogenic, targets of ANCA in AAV are proteinase-3 (PR3) and myeloperoxidase (MPO), ANCA against lysosome associated membrane protein-2 (LAMP-2), a lesser known ANCA antigen that is expressed on the glomerular endothelium, are present in some adults with AAV-associated renal disease. LAMP-2-ANCA has not been assessed in children with chronic systemic vasculitis, and, if present, would be a potentially valuable biomarker given that treatment decisions for these pediatric patients at diagnosis are largely informed by kidney function.MethodsA custom ELISA, using commercially available reagents, was designed to detect autoantibodies to human LAMP-2 in serum. Sera obtained from 51 pediatric patients at the time of diagnosis of chronic primary systemic vasculitis (predominantly AAV) were screened. LAMP-2-ANCA titers were evaluated for correlation with clinical metrics of disease activity (pediatric vasculitis activity score [pVAS], C-reactive protein [CRP] concentration, and erythrocyte sedimentation rate [ESR]), MPO- and PR3-ANCA titers, and renal function (glomerular filtration rate [GFR], renal-specific pVAS, and serum creatinine concentration).ResultsLAMP-2-ANCA (>1,000 ng/ml) were detected in 35% (n = 18) of pediatric systemic vasculitis patients, of which, 10 (20% of all patients) were found to have high positive titers (>1,500 ng/ml). Undetectable or negative titres (<500 ng/ml) were identified in 12% (n = 6) of patients, those with titers between 500 and 1,000 ng/ml were considered low with unknown clinical relevance (53%, n = 27). Although LAMP-2-ANCA titers did not significantly differ between patients with AAV versus ANCA-negative vasculitis, only AAV patients had high concentrations (>1,500 ng/ml) of LAMP-2-ANCA. LAMP-2-ANCA titers did not correlate with measures of disease activity (pVAS, CRP, or ESR) at the time of diagnosis. In contrast, for patients with 12-month post diagnosis follow-up, a negative correlation was observed between the change in GFR (from diagnosis to 12-month follow-up) and LAMP-2-ANCA titer at diagnosis.ConclusionsModerate to high LAMP-2-ANCA titers were detected in 35% (18/51) of children with chronic systemic vasculitis affecting small-to-medium vessels. Although the highest concentrations of LAMP-2-ANCA in this population were observed in individuals positive for classic ANCA (MPO- or PR3-ANCA), similar to previous reports on adult patients, LAMP-2-ANCA titers do not correlate with classic ANCA titers or with overall disease activity at diagnosis. Renal disease is a common manifestation in systemic small-medium vessel vasculitis (both in adults and children, though more severe in children) and our preliminary data suggest LAMP-2-ANCA at diagnosis may be a risk factor for more severe renal disease.

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Anti-neutrophil cytoplasmic antibodies (ANCA): Antigen interactions and downstream effects

Cited by 7 publications

References 124 publications

COVID‐19 and Immunological Dysregulation: Can Autoantibodies be Useful?

COVID‐19 and Immunological Dysregulation: Can Autoantibodies be Useful?

Antinuclear antibodies (ANAs) detected by indirect immunofluorescence (IIF) method in acute COVID-19 infection; future roadmap for laboratory diagnosis

Autoantibodies Against Lysosome Associated Membrane Protein-2 (LAMP-2) in Pediatric Chronic Primary Systemic Vasculitis

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