Autoantibodies to Lipocortin-1 Are Associated with Impaired Glucocorticoid Responsiveness in Rheumatoid Arthritis

Autoantibodies to the antiinflammatory protein lipocortin-1 have been found in patients with rheumatoid arthritis (RA) receiving oral glucocorticoids. The highest antibody titers correlated with a requirement for high maintenance doses of steroid (> 7.5 mg/day prednisolone). Forty-two patients with RA were grouped according to high or low autoantibody titer. In 18 patients, peripheral blood leukocyte counts and phenotypic analysis were performed before and 4 h after a single intravenous (iv) dose of 100 mg hydrocortisone. The group with low titer antibody exhibited a normal poststeroid peripheral blood lymphopenia, but the response in the group with high antibody titer was considerably blunted. In a 2nd study, 24 patients received 3 separate doses of 1000 mg iv methylprednisolone. After 8 weeks the group with the high titer antibody had shown no improvements in clinical or laboratory variables observed in the group with low titer antibody. Thus, the presence of high titer antilipocortin-1 antibody is associated with impaired responses to glucocorticoid therapy both in terms of clinical efficacy and effects on the immune system. This could explain the relative glucocorticoid resistance reported in a proportion of patients with RA.