The Clinical Relevance of Anti-DFS70 Autoantibodies

Despite all the progress in the establishment of specific autoantibody assays, screening for antinuclear antibodies (ANA) by indirect immunofluorescence on HEp-2 cells for quality-oriented laboratory diagnosis of ANA associated rheumatic diseases (AARD) remains indispensable but is not without limitations. Recent data on the relevance of the dense fine speckled (DFS) pattern and anti-DFS70 antibodies disclosed novel possibilities to optimize the serological stepwise diagnostics of AARD. The DFS pattern on HEp-2 cells is well differentiated from the classic "homogeneous" ANA pattern associated with dsDNA antibodies. This is the most frequent pattern in high titer ANA-positive healthy persons. The most characteristic ANA specificity associated with DFS pattern is the anti-DFS70 antibody (synonym LEDGF antibody). The prevalence of anti-DFS70 antibodies in AARD patients is significantly lower compared with the prevalence in ANA-positive healthy persons. There is a negative association between anti-DFS70 antibodies and AARD, especially if no concomitant AARD-specific autoantibodies are found. Isolated anti-DFS70 antibodies are detectable in less than 1 % of AARD but are detectable in 2-22 % of healthy persons. In the presence of an isolated anti-DFS70 antibody, the posttest probability for AARD is reduced significantly. The significance of anti-DFS70 antibodies as a criterion that helps to exclude AARD is also confirmed by follow-up studies on anti-DFS70 antibodies of positive, healthy individuals, who did not develop any AARD during a 4 year observation period. Consequently, anti-DFS70 antibodies are valuable novel biomarkers for better interpretation of positive ANA in cases of negative AARD-associated autoantibodies and should be integrated in modified test algorithms to avoid unnecessary referrals and examinations of ANA-positive persons.Tech Univ Dresden, Inst Immunol, Med Fac Carl Gustav Carus, Fetscherstr 74, D-01307 Dresden, GermanyUniv Fed Sao Paulo, Div Rheumatol, Immunorheumatol Lab, Escola Paulista Med, Sao Paulo, BrazilFleury Labs, Div Immunol, Sao Paulo, BrazilInova Diagnost Inc, Res & Dev, San Diego, CA 92131 USAUniv Fed Sao Paulo, Div Rheumatol, Immunorheumatol Lab, Escola Paulista Med, Sao Paulo, BrazilWeb of Scienc

Intravenous immunoglobulins (IVIG) in systemic sclerosis: a challenging yet promising future

The etiology and pathogenesis of systemic sclerosis are still largely unknown, but a variety of humoral and cellular autoimmune phenomena have been documented. In addition, the rarity of the disease, the broad spectrum of clinical manifestations, and the relevant risk of severe complications as well as the highly variable disease course render its management a major challenge. Some immunomodulatory agents have been used, but no single agent has given a convincing proof of effectiveness, and treatment has remained largely symptomatic through recent years. Novel therapies are currently being tested and may have the potential of modifying the disease process and overall clinical outcome. Efficacy of intravenous immunoglobulins (IVIG) in different regimens (1-2 g/kg of body weight, administered over 2-5 consecutive days) has been described in a limited number of trials and small case series, showing benefits in skin, articular, and lung interstitial disease symptoms. However, studies on IVIG in systemic sclerosis still remain few, and further randomized controlled trials should be undertaken to assess their clinical effectiveness or define the optimal dosage and times of administration