Furthermore, drug and anti-drug antibody complexes are not biologically active if the anti-drug antibodies are directed to the antigen-binding site, which is usually the only foreign part of humanised or fully human therapeutic antibodies. treatment with IFN (n=30), ETN (n=41) or ADA (n=28). Clinical data and systemic and local side effects were collected prospectively at baseline and after six months of anti-TNF treatment. Serum samples were taken at the same time points in order to measure antibodies against the TNF blockers, anti-nuclear (ANA) and anti-dsDNA antibodies. The IgA and IgM antibodies specific to all three anti-TNF- brokers were analysed using ImmunoCaP Phadia- Thermofisher especially developed in collaboration with the laboratory of Immunology and Allergy, San Giovanni di Dio, Florence. SCH 442416 The mean age of the 99 patients (86% females) was 54.612.4 years, and the median disease duration Rabbit Polyclonal to AIG1 was 11.2.3.2 years (range 3-14.3). The three treatment groups were comparable in terms of age, gender, rheumatoid factor and anti-citrullinated peptide (CCP) antibody positivity, and baseline C-reactive protein levels, erythrocyte sedimentation rate, 28-joint disease activity scores, and concomitant medications. Twelve patients treated with INF (40%) had anti-IFN IgM, and two (6%) anti-IFN IgA; 19 patients treated with ADA (68%) had anti-ADA IgM, and four (6%) anti-ADA IgA; and 27 patients treated with ETN (66%) had anti-ETN IgM, and 24 (58%) anti-ETN IgA. There were five systemic reactions in the IFN group, and seven adverse local reactions in both the ADA and the ETN group. There was no correlation between drug-specific IgA and IgM antibodies (p=0.65). There was also no correlation between the antibodies and disease activity after six months of treatment (r=0.189;p=0.32). Our findings show that this development of antibodies against IFN, ADA or ETN of IgA and IgM class are not related to any decrease in efficacy or early discontinuation of anti-TNF treatment in RA patients, nor to systemic and local reactions. Further studies of larger series of RA patients are needed to confirm the relationships between the development of drug-specific antibodies, serum TNF blocker levels, and disease activity. Keywords:TNF blockers, antibodies, adverse events, disease activity, rheumatoid arthritis. == INTRODUCTION == More than 400,000 patients throughout the world have been treated with anti-tumour necrosis factor (TNF) drugs (infliximab [IFN], etanercept [ETN], adalimumab [ADA]) because of rheumatoid arthritis (RA), psoriatic arthritis (PA) and seronegative spondyloarthritis. However, some questions concerning their safety have emerged since their approval because they can trigger immunisation, induce rare type I and III hypersensitivity, and cause acute and delayed reactions [1]. There have been many reports of reactions in patients receiving intravenous IFN, a chimeric IgG1K anti-TNF agent [2], and SCH 442416 immune-mediated side effects such as various cutaneous reactions have been encountered during therapy subcutaneous anti-TNF drugs. One recent paper has described injection site reactions in 29.3% patients treated with ETN [3]. The adverse reactions to biological brokers have been categorised into five types, including a complemented-mediated reaction with immediate IgE or delayed IgG antibody formation [4]. Biological therapeutic agents may be recognised by the human immune system as non-self and induce an immune response (also known as immunogenicity). Endogenous therapeutic proteins SCH 442416 such as erythropoietin and growth factors have amino acid sequences that are identical to those of the human equivalent and can be immunogenic as SCH 442416 a result of glycosylation or conformational changes that expose new epitopes. Therapeutic antibodies carry unique complementarity determining regions that contain stretches of sequences that are frequently recognised as foreign and induce the formation of anti-drug antibodies. This has clinical implications insofar as it can lead to adverse events, the most common of which are infusion reactions associated with a decrease in drug activity. A number of studies have shown that these antibodies play a role in the development of immunogenicity, but only a few have investigated the correlations between the different isotypes of immunoglobulin (Ig) and disease activity. The aim of this study was to evaluate the correlations between hypersensitivity reactions to biological brokers, disease activity and the development of class-specific IgA and IgM antibodies against the three TNF blockers. == METHODS == We evaluated 99 RA patients (30 treated with IFN, 28 with ADA, and 41 with ETN) with a mean age of 54.612.4 years and a median disease duration of 11.2.3.2 years (range 3-14.3). Eighty-six percent were females. The three treatment groups were comparable in terms of age, gender, SCH 442416 rheumatoid factor (RF) and anti-citrullinated peptide (CCP) antibody positivity, and baseline C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), 28-joint disease activity scores (DAS-28), and concomitant medications (Table1). == Table 1. == Characteristics of Patients Included in the Study SD= standard deviation; ERS= erythrocyte sedimentation rate; CRP=.