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Glucocorticoid receptor isoforms may show SLE disease activity
The expression of glucocorticoid receptor isoforms may present evidence of high disease activity and resistance to treatment with glucocorticoids in patients with systemic lupus erythematosus, according to newly published research.
Researchers studied data from 70 patients diagnosed with systemic lupus erythematosus (SLE) according to the American Rheumatism Association 1997 criteria for SLE and the SLE Disease Activity Index (SLEDAI) and 38 healthy control individuals matched for age and sex.
Patients were prescribed between 0.5 mg and 1 mg per kg per day of prednisone orally for 4 weeks in addition to oral hydroxychloroquine or another immunosuppressant to reduce glucocorticoid use gradually. Patients with 24-hour proteinuria of more than 3.5 g were given 800 mg of cyclophosphamide at least six times per month.
Patients were classified into one of two groups - the glucocorticoid-resistant (GCR) group or the glucocorticoid-sensitive (GCS) group - based on their response to prednisone. Those assigned to the GCS group were in remission or partial remission from clinical symptoms with a decrease in the SLEDAI score of at least four points from baseline, whereas patients in the GCR group had a lack of response to glucocorticoids, with a decrease in the SLEDAI score of less than four points from baseline.
Analysis of blood showed the expression of glucocorticoid receptor (GR) isoform GR-alpha averaged 51.85% of total GRs in patients with SLE and in controls, with expression found to be higher in the control group (68.8%). Further, the expression of GR-alpha was even lower in the GCR group that did not respond well to treatment. Patients with high disease activity also had lower expression of GR-alpha, which also correlated negatively with positive anti-dsDNA and antinuclear antibody titer, according to the researchers.
The collective findings suggest that low expression of GR-alpha could be a marker for disease activity and predictive of poor response to treatment with glucocorticoids, according to the researchers. - by Shirley Pulawski
Disclosure: The researchers report no relevant financial disclosures.