High plasma levels of adrenomedullin in collagen diseases

Abstract

Background: Adrenomedullin (ADM), a potent vasorelaxant/hypotensive peptide, was shown recently to be over-expressed in inflammatory rheumatic diseases. Objectives: The aim of this study was to investigate the value of ADM as a laboratory marker of disease activity in juvenile rheumatoid arthritis (JRA) and pediatric onset- systemic lupus erythematosus (SLE) and its relation to other markers of disease activity such as clinical scores, the ESR and tumor necrosis factor-α (TNF-α). Methods: The study included 24 patients with JRA, 17 with childhood onset- SLE, as well as, 19 with rheumatic arthritis and twenty clinically healthy age- and sex- matched subjects. Clinical evaluation for disease activity was performed using the clinical activity score index in JRA, and SLE-DAI in SLE. Subjects were investigated to verify the diagnosis and disease activity. Plasma ADM and serum of TNF-α levels were then assayed. Results: Serum TNF-α and plasma ADM levels were significantly higher in JRA and SLE patients than in rheumatic arthritis patients and healthy controls. Though serum TNF-α and plasma ADM levels were both higher in JRA (73.88 ± 11.6 pg/ml and 156.5 ± 22.4 pg/ml, respectively) compared to SLE (48.82 ± 7.5 pg/ml and 85.12 ± 15.7 pg/ml, respectively), the difference was of statistical significance only in ADM. Both serum TNF-α and plasma ADM levels were significantly higher in systemic onset-JRA (139.75 ± 18.5 and 260.25 &#177 28.6 pg/ml, respectively) compared to the pauciarticular-onset type (33.8 ± 3.04 and 93.4 ± 9.35 pg/ml, respectively), but comparable to the polyarticular onset cases (69.97 ± 8.45 and 149.87 ± 21.15 pg/ml, respectively). Positive correlations were noticed between plasma ADM and activity score index (r=0.72), ESR (r=0.59) and serum TNF-α (r=0.64) in JRA. The serum TNF- α was not influenced by the site of lupus activity unlike plasma ADM that was higher in subjects suffering from lupus arthritis or cardiovascular manifestations. The afore-mentioned markers correlated positively to the ESR in SLE but not to the SLE-DAI. With a cut-off value of TNF-α = 31 pg/ml and that for ADM = 80 pg/ml calculated from the results of the included rheumatic arthritis patients, ADM appeared to be a more sensitive marker of activity in JRA and SLE compared to TNF-α. Conclusion: Plasma ADM was over-expressed in JRA and SLE. It correlated with the clinical and biochemical activity markers in JRA suggesting that it can be used as an indicator of disease activity. In SLE, ADM levels correlated with ESR and TNF- α levels and it could be of value in identifying patients with arthritis and cardiac involvement.<br.

Keywords: Adrenomedullin, JRA, SLE, TNF-α, arthritis

Egypt J Pediatr Allergy Immunol 2004; 2(1): 28-36