New-onset IgG autoantibodies in hospitalized patients with COVID-19

Chang, Sarah; Feng, Allan; Meng, Wenzhao; Apostolidis, Sokratis A.; Mack, Elisabeth; Artandi, Maja; Barman, Linda; Bennett, Kate; Chakraborty, Saborni; Chang, Iris; Cheung, Peggie; Chinthrajah, Sharon; Dhingra, Shaurya; Do, Evan; Finck, Amanda; Gaano, Andrew; Geßner, Reinhard; Giannini, H.M.; González, Joyce; Greib, Sarah; Gündisch, Margrit; Hsu, Alexander; Kuo, Alex; Manohar, Monali; Mao, Rong; Neeli, Indira; Neubauer, Andreas; Oniyide, Oluwatosin; Chen, Alex; Puri, Rajan; Renz, Harald; Schapiro, Jeffrey M.; Weidenbacher, Payton A.; Wittman, Richard; Ahuja, Neera; Chung, Ho‐Ryun; Jagannathan, Prasanna; James, Judith A.; Kim, Peter; Meyer, Nuala J.; Nadeau, Kari; Radic, Marko; Robinson, William H.; Singh, Upinder; Wang, Taia T.; Wherry, E. John; Skevaki, Chrysanthi; Prak, Eline T. Luning; Utz, Paul J.

doi:10.1038/s41467-021-25509-3

Cited by 317 publications

(334 citation statements)

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“…In the observation with the context of severe COVID-19, numerous antibody secreting cells are produced as a result of upregulation of extrafollicular B cells, including clonotypes that are autoreactive ( Woodruff et al, 2020 ). Considering these data in cellular structuring, ANA was detected in 18% of COVID-19 patients in our study, but this was lower than the data in the literature (21.3%–64%) ( Pascolini et al, 2021 ; Gazzaruso et al, 2020 ; Lerma et al, 2020 ; Sacchi et al, 2020 ; Chang et al, 2021b ; Chang et al, 2021a ; Trahtemberg et al, 2021 ). The relationship between disease severity or the time of sampling and antibody titers were not significant, but the majority of ANAs were strongly positive at a titer of 3+.…”

Section: Discussioncontrasting

confidence: 89%

“…Although various ANA patterns have been detected in the initiation of COVID-19, the presence of patterns directed mainly against nuclear antigens has been reported ( Lerma et al, 2020 ; Chang et al, 2021b ; Chang et al, 2021a ). In agreement with the literature, mainly nucleolar patterns were detected in our study.…”

Section: Discussionmentioning

confidence: 99%

“…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 ).…”

Section: Discussionmentioning

confidence: 99%

“…Nuclear antigens are usually the target of autoantibodies and anti-nuclear antibodies (ANA) can be detected in many autoimmune diseases such as systemic lupus erythematosus (SLE), but also in many viral infections ( Sener et al, 2014 ). Although there are several studies in the literature, autoantibodies are commonly seen in COVID-19 patients (21.3%–64%), but larger studies are needed to investigate their association with disease prognosis ( Pascolini et al, 2021 ; Gazzaruso et al, 2020 ; Lerma et al, 2020 ; Sacchi et al, 2020 ; Chang et al, 2021b ; Chang et al, 2021a ; Trahtemberg et al, 2021 ). However, because ANA is also positive in the healthy population (with a weak titer and prevalence ranging from 8% to 15%) and in other clinical conditions, positive results must be interpreted with clinical data ( Kaklıkkaya et al, 2020 ; Yurttutan Uyar et al, 2017 ; Damoiseaux et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…Recent studies have demonstrated the significant breadth of emerging autoreactivity in severe SARS-CoV-2 infection [1][2][3] . More specifically, we have identified a relaxation of peripheral tolerance within early antibody secreting cells that emerge in patients with COVID-19 as important drivers of those responses 2 .…”

Section: Main Textmentioning

confidence: 99%

Inflammation and autoreactivity define a discrete subset of patients with post-acute sequelae of COVID-19, or long-COVID

Woodruff

Walker

Truong

et al. 2021

Preprint

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Recent studies have demonstrated the significant breadth of emerging autoreactivity in severe SARS-CoV-2 infection. Importantly, we have identified a relaxation of peripheral tolerance within early antibody secreting cells that emerge in patients with COVID-19 as important drivers of those responses. While often viral-specific, these extrafollicular-derived cells also display cross reactivity to autoantigens present in the inflammatory lung environment, and despite resolution of most autoreactivity within 6 months, they persisted in some patients. These results raise questions regarding autoreactive antibodies that arise during acute SARS-CoV-2 infection and their persistence in patients with symptoms in Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Through clinical autoreactive antibody screening of 95 patients with PASC and no history of autoimmune disease, we identify significant autoreactive profiles in patients with ongoing symptoms post-recovery, with 80% of patients returning positive tests for at least one autoantigen, and 40% showing breaks in tolerance to 2 or more. Anti-nuclear antigen positivity was most common, displaying positivity in 63% of patients, however, positive tests were broad and included reactivities against carbamylated protein responses, RNA polymerase III, and phospholipids. We also identify patients with reactivity against dsDNA in the PASC cohort -- a reactivity not observed in acute infection even in the critically ill. These results demonstrate evidence of serum autoantibodies in patients who present to PASC clinics with persistent symptoms up 14 months following SARS-CoV-2 infection, and further confirm the growing linkage between COVID-19 and observed clinical autoreactivity -- even into the recovery phase of disease.

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Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events

et al. 2023

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ImportanceThe prevalence of antiphospholipid antibodies (aPL) and their association with future atherosclerotic cardiovascular disease (ASCVD) risk has yet to be thoroughly investigated.ObjectiveTo determine the association between measurements of aPL at a single time point and ASCVD risk in a diverse population.Design, Setting, and ParticipantsThis cohort study measured 8 aPL (anticardiolipin [aCL] IgG/IgM/IgA, anti–beta-2 glycoprotein I [aβ2GPI] IgG/IgM/IgA, and antiphosphatidylserine/prothrombin [aPS/PT] IgG/IgM) by solid-phase assays in plasma from participants of the Dallas Heart Study (DHS) phase 2, a multiethnic, population-based cohort study. Blood samples were collected between 2007 and 2009. The median follow-up was 8 years. Statistical analysis was performed from April 2022 to January 2023.Main Outcomes and MeasuresAssociations of aPL with future ASCVD events (defined as first nonfatal myocardial infarction, first nonfatal stroke, coronary revascularization, or death from cardiovascular cause) were assessed by Cox proportional hazards models, adjusting for known risk factors, medications, and multiple comparisons.ResultsAmong the 2427 participants (mean [SD] age, 50.6 [10.3] years; 1399 [57.6%] female; 1244 [51.3%] Black, 339 [14.0%] Hispanic, and 796 [32.8%] White), the prevalence of any positive aPL tested at a single time point was 14.5% (353 of 2427), with approximately one-third of those detected at a moderate or high titer; aCL IgM had the highest prevalence (156 individuals [6.4%]), followed by aPS/PT IgM (88 [3.4%]), aβ2GPI IgM (63 [2.6%]), and aβ2GPI IgA (62 [2.5%]). The IgA of aCL (adjusted hazard ratio [HR], 4.92; 95% CI, 1.52-15.98) and aβ2GPI (HR, 2.91; 95% CI, 1.32-6.41) were independently associated with future ASCVD events. The risk further increased when applying a positivity threshold of at least 40 units (aCL IgA: HR, 9.01 [95% CI, 2.73-29.72]; aβ2GPI IgA: HR, 4.09 [95% CI, 1.45-11.54]). Levels of aβ2GPI IgA negatively correlated with cholesterol efflux capacity (r = −0.055; P = .009) and positively correlated with circulating oxidized LDL (r = 0.055; P = .007). aβ2GPI IgA–positive plasma was associated with an activated endothelial cell phenotype as evidenced by increased surface expression of surface E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1.Conclusions and RelevanceIn this population-based cohort study, aPL detectable by solid-phase assays were present in a substantial proportion of adults; positive aCL IgA and aβ2GPI IgA at a single time point were independently associated with future ASCVD events. Longitudinal studies with serial aPL measurements are needed to further explore these findings.

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New-onset IgG autoantibodies in hospitalized patients with COVID-19

Cited by 317 publications

References 61 publications

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

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

Inflammation and autoreactivity define a discrete subset of patients with post-acute sequelae of COVID-19, or long-COVID

Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events

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