ROC curves were generated by plotting sensitivity against 1-specificity as the cutpoint is varied over the entire range of index values from a disease group (in this case FS patients) and a negative control group (US controls). al. /em , 1986a; Stanley em et al. /em , 1986b). FS patients usually live in rural areas of certain states of Brazil where the prevalence of disease is higher than in urban communities (Diaz em et al. /em , 1989b). The disease exhibits a strong association with the HLA-DRB1*0102, 0404 and 1402 alleles (Moraes em et al. /em , 1997). It is thought that an environmental antigen(s) may trigger FS (Flores em et al. /em , 2009). One of the relevant target antigens in both PF and FS is the desmosomal cadherin, Dsg1 (Buxton em et al. /em , 1993; Stanley em et al. /em , 1986a). Desmosomal cadherins are transmembrane glycoproteins that are critical components of the desmosome, one of the keratinocyte intercellular junctions (Desai em et al. /em , 2009). They include the desmogleins (Dsg) and desmocollins (Dsc), each with well characterized isoforms; four of Dsg (Dsg1C4) and three of Dsc (Dsc1C3) (Thomason em et al. /em , 2010). Desmosomal Tirbanibulin Mesylate cadherins are structurally and functionally similar to the classic E-cadherin, which is the molecular component of the adherens junction. Adherens junctions are structurally located in the interdesmosomal regions of the keratinocyte cell surface (Green em et al. /em , 2010). IgG anti-desmosomal autoantibodies from PF and FS sera are routinely Rabbit Polyclonal to Cyclin H (phospho-Thr315) detected by indirect immunofluorescence (IF), which for decades have been utilized as a diagnostic test for these diseases. The application of ELISA techniques using recombinant human Dsg1 has improved diagnostic accuracy (Amagai em et al. /em , 1999) and made it possible to test large numbers of individuals living in communities where FS is endemic (Qaqish em et al. /em , 2009; Warren em et al. /em Tirbanibulin Mesylate , 2003). ELISA studies have also identified IgG4 anti-Dsg1 autoantibodies as a serological predictor of FS (Qaqish em et al. /em , 2009; Warren em et al. /em , 2003). Moreover, anti-Dsg1 autoantibodies of the IgM (Diaz em et al. /em , 2008) and IgE (Qian em et al. /em , 2011) class have also been detected in the sera of a large number of FS patients, suggesting an ongoing environmental trigger. While anti-Dsg1 IgG and IgG4 autoantibodies Tirbanibulin Mesylate have been shown to be pathogenic in PF and FS (Rock em et al. /em , 1989), there have been reports of autoantibody responses Tirbanibulin Mesylate to other members of the cadherin family of proteins in certain pemphigus phenotypes. Dsg3 is diagnostic and pathogenically relevant in pemphigus vulgaris (PV) (Amagai em et al. /em , 1991), while Dsc antigens may be relevant in IgA pemphigus (Duker em et al. /em , 2009) and certain forms of PV (Mao em et al. /em , 2010). Autoantibodies against Dsg4 (Nagasaka em et al. /em , 2004) and E-cadherin (Evangelista em et al. /em , 2008) have also been described in PV and PF, respectively. It is accepted that the desmosome, specifically its structural component Dsg1, is the target of pathogenic IgG4 polyclonal autoantibodies generated by FS patients. The IgG response in FS is complex and may result from exposure to environmental antigens and/or to self Dsg1. Moreover, the final pathogenic IgG4 response may evolve via phenomena such as crossreactivity with other desmosomal cadherins and/or epitope spreading. The aim of this study, therefore, was to determine the IgG autoantibody profile for each of the eight keratinocyte cadherins in a large number of subjects from three groups, i.e. FS patients, healthy individuals from US (US controls) and healthy individuals living in an endemic area.