Auto-antibodies against type I IFNs in > 10% of critically ill COVID-19 patients: a prospective multicentre study.

BACKGROUND: Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs. RESULTS: We conducted a prospective multicentre cohort study including patients admitted in 11 intensive care units (ICUs) from Great Paris area hospitals with proven SARS-CoV-2 infection and acute respiratory failure. 925 critically ill COVID-19 patients were included. Auto-Abs neutralizing type I IFN-α2, ß and/or ω were found in 96 patients (10.3%). Demographics and comorbidities did not differ between patients with versus without auto-Abs. At ICU admission, Auto-Abs positive patients required a higher FiO2 (100% (70-100) vs. 90% (60-100), p = 0.01), but were not different in other characteristics. Mortality at day 28 was not different between patients with and without auto-Abs (18.7 vs. 23.7%, p = 0.279). In multivariable analysis, 28-day mortality was associated with age (adjusted odds ratio (aOR) = 1.06 [1.04-1.08], p < 0.001), SOFA score (aOR = 1.18 [1.12-1.23], p < 0.001) and immunosuppression (aOR = 1.82 [1.1-3.0], p = 0.02), but not with the presence of auto-Abs (aOR = 0.69 [0.38-1.26], p = 0.23). CONCLUSIONS: In ICU patients, auto-Abs against type I IFNs were found in at least 10% of patients with critical COVID-19 pneumonia. They were not associated with day 28 mortality.

IgA anti-beta-2 glycoprotein I antibodies in chronic hepatitis C.

BACKGROUND AND STUDY AIMS: Antiphospholipid antibodies (aPL) have been reported not only in various autoimmune conditions but also in other infections, such as chronic hepatitis C (CHC) infection. The aim of this study is to evaluate the frequency of aPL in patients with CHC. PATIENTS AND METHODS: Ninety-six CHC patients and 90 healthy blood donors (HBD) were studied. Fifty-three of the patients were under treatment, and 43 had not yet received any treatment. IgG, IgA, and IgM antibodies against cardiolipin (aCL) and beta-2 glycoprotein I (aß2GPI) were detected by ELISA. RESULTS: We found that the frequency of aPL (aCL and/or aß2GPI) was significantly higher in CHC patients than in controls (51% vs 11.1%, p <10-6). The frequencies of aCL and aß2GPI were significantly higher in patients than in HBD (27.1% vs 5.5%, p < 10-3, and 44.8% vs 11.1%, p < 10-6, respectively). The isotype distribution of aCL and aß2GPI demonstrated that aCL-IgG and aß2GPI-IgA were more frequent in patients than in healthy subjects (21.9% vs 2.2%, p < 10-3, and 38.5% vs 7.8%, p < 10-6, respectively). In CHC patients, the frequency of aß2GPI was significantly higher than that of aCL (44.8% vs 27.1%, p = 0.01). aß2GPI-IgA was significantly more frequent than aß2GPI-IgG (38.5% vs 7.3%, p <10-6), aß2GPI-IgM (38.5% vs 9.4%, p <10-3), and aCL-IgG (38.5% vs 21.9%, p = 0.01). No difference in aPL frequency was observed between the treated and untreated patients. CONCLUSION: On the basis of the findings of this study, aPL, particularly aß2GPI-IgA and aCL-IgG, are frequent in CHC patients.

Anti-gp210 and anti-Sp100 antibodies in primary biliary cholangitis.

BACKGROUND AND STUDY AIMS: To determine the sensitivity and specificity of anti-gp210 and anti-Sp100 autoantibodies in primary biliary cholangitis (PBC) PATIENTS AND METHODS: Sera of 106 PBC patients with positive anti-mitochondrial antibodies and 58 healthy blood donors were analyzed. A line immunoassay was used to evaluate the reactivity of anti-gp210 and anti-Sp100 antibodies. RESULTS: The frequency of anti-gp210 and anti-Sp100 autoantibodies was 29.2% and 28.3%, respectively. Eight patients had both anti-gp210 and anti-Sp100 antibodies. Of 106 patients, 23 (21.7%) had anti-gp210 antibody, although not anti-Sp100 antibody, and 22 (20.7%) had anti-Sp100, although not anti-gp210 antibodies. Their combination increased the frequency of anti-gp210 and anti-Sp100 antibodies from 29.2% to 50% (P = 0.002) and 28.3% to 50% (P = 0.0012), respectively. In the control group, two subjects had anti-gp210 antibody and none had anti-Sp100 antibody. Thus, the specificity of anti-gp210 and anti-Sp100 antibodies was 96.5% and 100%, respectively. The positive predictive value (PPV) of anti-gp210 antibody was 94%; its negative predictive value (NPV) was 42.7%. The PPV and NPV of anti-Sp100 antibody were 100% and 43.3%, respectively. CONCLUSION: It is important to combine anti-gp210 and anti-Sp100 antibodies in the immunological exploration of PBC.