The sensitivity of this assay for anti-nuclear antibodies in systemic autoimmune disease is similar to that of other methods [[16], [17], [18], [19]]. We detected anti-nuclear antibodies in 25% (16/64) of COVID-19 patients using manufacturer-recommended thresholds. antibody, Antiphospholipid antibody Highlights ? Autoantibodies against nuclear antigens are detectable in Luteoloside 25% of patients hospitalized with acute COVID-19. ? Anti-nuclear antigen antibodies were weakly reactive and most often directed to single antigens. ? Vasculitis-associated autoantibodies were not detected in specimens from patients with acute COVID-19. ? Anti-phospholipid antibodies were infrequently detected in patients with acute COVID-19. 1.?Introduction Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a recently emergent, now pandemic virus and etiological agent of Coronavirus Induced Disease-19 (COVID-19) [1,2]. Luteoloside SARS-CoV-2 infection is characterized by a wide range of clinical outcomes, from asymptomatic infection to severe lower respiratory tract damage and acute respiratory distress syndrome (ARDS) [3]. Lethal disease is often associated with sepsis, coagulopathy, multi-organ failure and heightened inflammatory responses, including cytokine storm syndrome [4]. In addition, a myriad of other clinical associations have been described, including autoimmune phenomena such as Kawasaki-like syndrome, multisystem inflammatory syndrome, Guillain Barre syndrome, immune thrombocytopenic purpura and chilblain-like lesions [5,6]. Immune mechanisms likely play a significant component to the pathogenesis of disease in COVID-19. SARS-CoV-2 infection may trigger development of autoimmunity in susceptible patients, potentially as a result of viral cross-reactivity with autoantigens [7,8]. Nuclear antigens are commonly targeted by autoantibodies, and antinuclear antibodies are a hallmark of multiple autoimmune diseases, including systemic lupus erythematosus [9]. Reactivity to more than one nuclear antigen is characteristically found in specimens from patients with autoimmune diseases. Recent data from small studies suggest a high prevalence of antibodies against nuclear antigens in severe COVID-19, detectable in 92% of 11 ICU patients in a study from Germany [10] and 50% of 21 ICU patients in a study from China [11]. In addition to nuclear antigens, many other self-antigens can be targeted by autoantibodies in association with diverse autoimmune phenomena, including vasculitis and thrombosis. Histologic evidence of vasculitis has been described in COVID-19, suggesting the possibility that autoimmune-mediated vessel diseases may occur [12,13]. In addition, coagulopathy and thrombosis is a prominent feature of severe COVID-19 [14]. Case reports suggest that antiphospholipid antibodies can mediate autoimmune thrombosis in this disease [15]. We sought to better understand the prevalence of autoantibody responses in acute COVID-19, and measured antibodies against nuclear, vasculitis-associated, and phospholipid antigens in specimens from patients hospitalized at our institution. 2.?Methods 2.1. Study design and participants Remnant serum and plasma specimens from 64 patients with RT-PCR confirmed SARS-CoV-2 infection were collected from the clinical laboratories at the University of Washington and Harborview Medical Centers in Seattle, Washington between March and May of 2020. Specimens were collected under an IRB-approved waiver of consent and stored at ?80??C before autoantibody testing. Samples from healthy blood donors in our region obtained prior to the COVID-19 pandemic were used as normal controls. Medical records were reviewed for history of autoimmune diseases and lab values. When available, the white blood cell count (WBC), C-reactive protein (CRP), ferritin, fibrinogen, and interleukin-6 (IL-6) values were recorded for the date closest to specimen collection within a two-week window in the same hospitalization. 2.2. Anti-nuclear antibody detection Antibodies to nuclear antigens were detected using the BioPlex 2200 antinuclear antibody (ANA) screen multiplex autoimmune assay (Bio-Rad Laboratories). This system measures IgG autoantibodies to the following antigens: double-stranded DNA (dsDNA), centromere B, chromatin, ribosomal protein, SS-A Luteoloside (including both Ro52 and Ro60), SS-B, Sm, Sm/RNP, ribonucleoprotein (RNP), Scl-70/topoisomerase I, and Rabbit Polyclonal to MAP2K3 (phospho-Thr222) Jo-1. Quantitative results were expressed as an antibody index (AI) for all antigens except dsDNA, which is reported in IU/mL. For our initial analysis, we used the manufacturers suggested thresholds, which define <1.0 AI as negative and 1.0 AI as positive for antibodies to centromere B, chromatin, ribosomal protein, SS-A, SS-B, Sm, Sm/RNP, RNP, Scl-70, and Jo-1. The manufacturers suggested ranges for antibodies to dsDNA are 4 IU/mL (negative); 5C9 IU/mL (indeterminate) and 10 IU/mL (positive). Our clinical laboratory has established modified cutoffs for result reporting, based on testing specimens from 264 healthy regional blood donors. Samples with values??
The sensitivity of this assay for anti-nuclear antibodies in systemic autoimmune disease is similar to that of other methods [[16], [17], [18], [19]]