Serum Baff levels are increased in patients with Myositis and Anti-JO-1 Antibodies -OP0056
Authors: O. Krystufkova 1, T. Vallerskog 2, S.B. Helmers 2, H. Mann 1, I. Putova 1, V. Malmstrom 2, C. Trollmo 2, J. Vencovsky 1, I.E. Lundberg 2. 1Immunology and Clinical Department, Institute of Rheumatology, Prague, Czech Republic, 2Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
Background:
Autoantibodies are frequently present in patients with myositis. The most common myositis specific autoantibody is anti-Jo-1, which is associated with a distinct clinical phenotype including interstitial lung disease (ILD), Raynaud's phenomenon, arthritis, and skin changes. The cytokine BAFF (B-cell activation factor of the TNF family- also known as BLyS) is crucial for B–cell maturation and survival, and also plays a role in T-cell activation and differentiation. High serum levels have been reported in patients with various autoimmune diseases such as Sjögren's syndrome, SLE and RA. This group previously observed elevated serum levels of BAFF in patients with myositis, and this work represents the results from an extended group of patients.
Objectives:
To investigate serum levels of BAFF in patients with myositis and to determine if they correlated to clinical phenotype or autoantibody profile.
Methods:
Sera from 45 patients with polymyositis (PM), 49 with dermatomyositis (DM), 6 with inclusion body myositis (IBM), and 30 matched controls were evaluated for BAFF levels by ELISA. Autoantibodies were detected by line-blot assay. Serum levels of CRP and creatine phosphokinase (CPK) were available from 80 samples.
Results:
Autoantibodies to Jo-1, Mi-2, PM-Scl and/or Ro were present in 63 out of 100 patients. Thirty-nine patients were anti-Jo-1 positive. Forty-three patients had interstitial lung disease (ILD). BAFF levels in serum were elevated in myositis patients (median: 1.12 ng/ml) when compared to healthy controls (0.85 ng/ml, p=0.0025). Higher BAFF levels were found in patients with DM (1.25 ng/ml) compared to PM (0.9 ng/ml, p<0.05) and controls (p<0.001). Patients with anti Jo-1, but not those with Mi-2 or PM-Scl autoantibodies, had significantly higher median levels of BAFF (1.42 ng/ml) in comparison with healthy controls (p<0.001). Patients with ILD had higher serum BAFF levels (1.29 ng/ml) when compared to controls (p<0.01). Patients with high serum levels of BAFF had significantly higher CPK and CRP levels, and BAFF levels correlated with CPK levels (r=0.38, p<0.0004).
Conclusion:
Circulating BAFF levels were elevated in sera of patients with myositis. The highest levels were found in dermatomyositis and in those patients who were anti-Jo-1 positive. Furthermore, the correlation with markers of disease activity, the presence of ILD, CRP and CPK levels could indicate that BAFF is important in the pathogenesis of myositis and may be important in B cell activation in these patients.
Comment:
This study completes earlier work by this group who has previously shown elevated levels of BAFF (B cell activation factor of the TNF family) in myositis, as is seen in other autoimmune diseases. This study utilized 100 patients with IIM and 30 matched controls to evaluate for elevated BAFF levels. The intent, to correlate BAFF levels with clinical phenotype or autoantibody profile, was accomplished. The investigators found that the highest levels of serum BAFF levels were seen in patients who were Jo-1 positive, had DM, had ILD, and had higher levels of CPK and CRP. This raises the possibility that BAFF is implicated in the pathogenesis in at least some disease subsets of myositis. Once again, BAFF may be a potential target for therapy in at least some subtypes of myositis.