In this article, we present a comparative immunohistochemical evaluation of four clinical-stage antibodies (L19, F16, G11 and F8) directed against splice isoforms of fibronectin and of tenascin-C for ...their ability to stain synovial tissue alterations in rheumatoid arthritis patients. Furthermore we have evaluated the therapeutic potential of the most promising antibody, F8, fused to the anti-inflammatory cytokine interleukin (IL) 10.
F8-IL10 was produced and purified to homogeneity in CHO cells and shown to comprise biological active antibody and cytokine moieties by binding assays on recombinant antigen and by MC/9 cell proliferation assays. We have also characterized the ability of F8-IL10 to inhibit arthritis progression in the collagen-induced arthritis mouse model.
The human antibody F8, specific to the extra-domain A of fibronectin, exhibited the strongest and most homogenous staining pattern in synovial biopsies and was thus selected for the development of a fully human fusion protein with IL10 (F8-IL10, also named DEKAVIL). Following radioiodination, F8-IL10 was able to selectively target arthritic lesions and tumor neo-vascular structures in mice, as evidenced by autoradiographic analysis and quantitative biodistribution studies. The subcutaneous administration route led to equivalent targeting results when compared with intravenous administration and was thus selected for the clinical development of the product. F8-IL10 potently inhibited progression of established arthritis in the collagen-induced mouse model when tested alone and in combination with methotrexate. In preparation for clinical trials in patients with rheumatoid arthritis, F8-IL10 was studied in rodents and in cynomolgus monkeys, revealing an excellent safety profile at doses tenfold higher than the planned starting dose for clinical phase I trials.
Following the encouraging preclinical results presented in this paper, clinical trials with F8-IL10 will now elucidate the therapeutic potential of this product and whether the targeted delivery of IL10 potentiates the anti-arthritic action of the cytokine in rheumatoid arthritis patients.
To determine the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in systemic sclerosis (SSc) and to assess any association between the presence of anti-CCP, radiographic features, ...and clinical manifestations.
Anti-CCP antibodies and rheumatoid factor (RF) were tested in serum samples from 75 patients with SSc (64 women and 11 men), with a mean age of 59.4 years (range 24-85) with either diffuse (dcSSc) and limited (lcSSc) cutaneous involvement. As a control group, 22 age- and sex-matched healthy controls (HCs) were examined. Standard radiographs of the hands and wrists were examined in each patient.
The presence of anti-CCP was found in sera of 10.6% (8/75) patients with SSc (lcSSc 3 of 44, 6.8%; dcSSc 5 of 31, 16.1%). None of the HCs was positive for anti-CCP. The positivity of RF was observed in 19 of 75 (25.3%) SSc patients (lcSSc 10 of 44, 22.7%; dcSSc 9 of 31, 29%). Statistically significant association was found between anti-CCP positivity and the presence of arthritis (p<0.0001) and marginal erosions (p=0.001).
Our data show that joint involvement is a common presenting feature of SSc. In this report, we show that anti-CCP antibodies can be detected also in patients with SSc, but they are generally less commonly present than in adults with rheumatoid arthritis (RA). Thus, the finding of high titers of anti-CCP antibodies may help to define the diagnosis of overlap syndrome SSc/RA and facilitate diagnosis and appropriate treatment.
Background Acne fulminans is the most severe form of inflammatory acne characterized by the acute onset of inflammatory nodules and plaques, most commonly on the chest and the back. The lesions ...undergo rapid suppuration, leaving ragged hemorrhagic ulcers. Typically, it affects adolescent males with a history of mild to moderate acne. The affected patients often have constitutional symptoms such as fever, malaise, arthralgias, and myalgias. Leukocytosis is commonly associated. Sacroiliitis is reported in 21% of acne fulminans patients in association with arthritis and in a few cases it is reported during isotretinoin treatment, suggesting the drug triggering.
Conclusion We report a case of a young male patient in whom the induction of acne fulminans by systemic isotretinoin was associated with unilateral sacroiliitis.
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