Laboratory measurement of autoantibodies to Annexin A1: Review and measurements in health and COVID-19

Annexin A1, a protein released by neutrophils, is a potent regulator of inflammation in the intact form, but loses this activity when cleaved. The presence of autoantibodies to this protein can impact its function. An immunoassay, developed to measure autoantibodies to Annexin A1 in plasma or serum, has been developed and performances are reported. The cut-off for the positive range is determined from the mean value and standard deviations measured in a healthy group. Anti-Annexin A1 autoantibodies were then tested in hospitalized COVID-19 patients, at baseline or at any time during hospitalization. Sixty-one out of 379 patients tested positive for at least one isotype, IgG, IgA, or IgM. Few patients presented with only 1 isotype (2 G, 12 A, 16 M), but the combination of 2 isotypes was observed in many of them, and 3 expressed the 3 isotypes all together. Some association was noted between the presence of these autoantibodies and the development of thrombosis or admission in Intensive Care Units. The specific clinical complication risk associated to each isotype is yet to be established as our study was mainly transversal. Complementary studies are required to better evaluate the diagnostic or prognostic values of the anti-Annexin A1 autoantibodies, which have already been reported in various clinical situations. They could potentially reduce the anti-inflammatory regulation potential of Annexin A1, a mechanism which could contribute to disease evolution and worsening.