https://doi.org/10.3390/antib11040077. Lande, R; Palazzo, R; Mennella, A; Pietraforte, I; Cadar, M; Stefanantoni, K; Conrad, C; Riccieri, V; Frasca, L. occasionally, and some of these autoantibodies can target LL37, an antimicrobial peptide (AMP) over-expressed in psoriatic lesional skin [3,6,7]. LL37 is known to be an autoantigen for T-cells of both the CD4 and CD8 phenotype in psoriasis [6]. Interestingly, in the arthritis associated with psoriasis, psoriatic arthritis (PSA), antibodies that also target post-translational modified autoantigens are present [7]. Anti-carbamylated or anti-citrullinated protein is present in PSA, including autoantibodies to LL37, which also recognize carbamylated and citrullinated LL37 (carb-LL37 and cit-LL37) [3,7]. Of note, anti-citrullinated protein antibodies (ACPAs), which are typically considered markers of rheumatoid arthritis (RA) [8], can be also detected in the blood of systemic lupus erythematosus (SLE) patients [9]. Interestingly, we described in SLE the presence of anti-LL37 antibodies and later we found that anti-cit-LL37 and anti-carb LL37 antibodies are also present in SLE [10,11,12]. Thus, these results have shown that anti-carbamylated and anti-citrullinated proteins are not only a feature of RA but are present in PSA, psoriasis, and SLE; this may suggest common mechanisms in the pathogenesis of these diseases. Overall, these examples indicate that autoimmune diseases that seem to be different, as they present with different clinical manifestations, may share antibody reactivity. Therefore, an understanding of the reasons why some antibodies mark only specific diseases whereas others are shared between diseases that affect different body locations could be very helpful in shedding light on common pathogenic pathways and, ultimately, repositioning pharmacological interventions. Moreover, the study of new, old, and shared antibody specificities across several autoimmune diseases can help in identifying more precise and distinct biomarkers in autoimmunity, even in less-studied autoimmune disorders. SNT-207858 By an extension of this field of studies, it is also interesting to study a different kind of antibody specificity detected in autoimmune (or autoinflammatory) diseases that is not directly linked to the type of auto-reactivity in that specific disease but induced as a consequence of a biological therapy. One of these SNT-207858 examples concerns antibodies generated during anti-TNF-alpha therapy (anti-TNFs). Anti-TNFs have become a benchmark in the treatment of numerous autoimmune diseases: ankylosing spondylitis (AS), RA, hidradenitis suppurativa, Crohns disease (CD), polyarticular juvenile idiopathic arthritis, ulcerative colitis (UC), uveitis, PsA, and psoriasis [13,14]. Five anti-TNF brokers are currently FDA-approved for the treatment of many joint- and gut-related inflammatory conditions: etanercept (composed of the TNFR2 fused to a human IgG1 Fc domain name), infliximab (humanCmurine chimeric monoclonal IgG1 antibody), adalimumab (fully human antibody), certolizumab pegol (PEGylated Fab fragment of a humanised monoclonal antibody), and golimumab (fully human antibody) [13]. Although scientific efforts have been focused on antibody engineering in order to reduce the immunogenicity of biological drugs, the development of anti-drug-antibodies (ADAs) still forms the basis of the ineffectiveness or adverse reactions seen in a percentage of patients. Theoretically, ADAs are expected to affect treatment efficacy by lowering exposure to the free active drug via neutralization and/or enhanced clearance. When enough free drug is usually available to bind to its biological target, even when present, ADAs may not have clinical consequences [15]. Immediately after their introduction into Mouse monoclonal to XBP1 the treatment protocols of several autoimmune and rheumatic diseases, scientific studies analyzed the immunogenicity of TNF inhibitors, showing a shorter drug survival in patients after subsequent doses of anti-TNFs [16]. Most anti-TNFs induce the formation of ADAs. As described above, TNF inhibitors are now widely used and have greatly improved medical care for patients. However, about 20% of psoriasis patients do not respond to treatment with TNF inhibitors, and around one third of initial responders drop their response over time [17]. Similar profiles have been observed for patients with RA and with inflammatory bowel disease (IBD) [18]. This limitation to the clinical efficacy of anti-TNF therapy can be explained by the immunogenicity potential of these drugs, considering that even humanized and fully human monoclonal antibodies can still induce ADA formation. 2. Overview of the Published Articles in the Special Issue [27] and also in the inactivation of bacterial toxins during contamination [43]. Acknowledgments A.M.s salary is paid via a FOREUM research grant to L.F. We thank all the contributors to the Special Issue. Funding Statement FOREUM SNT-207858 2020-2023 research grant to L.F. Author Contributions Conceptualization, L.F. methodology, L.F. writingoriginal draft preparation, L.F., A.M. and R.P.; writingreview.