Disease specificity of anti-tryptophan hydroxylase-1 and anti-AIE-75 autoantibodies in APECED and IPEX syndrome

Gastrointestinal immunity against tryptophan hydroxylase-1, aromatic L-amino-acid decarboxylase, AIE-75, villin and Paneth cells in APECED

“…This finding can be taken as an indirect evidence for T-cell mediated immune destruction. Very recently, in their series of 23 patients with APECED, Chida et al [31] found anti-villin antibodies in only 13% of their APECED patients (3/23) and no circulating antibodies against AIE-75. As the AIE-75 is the main target for autoantibodies in IPEX, where the escape from immunological tolerance is peripheral, probably due to the lack of proper regulatory T-cell function, the authors suggested that also in APECED, a tolerance failure to AIE-75 would be due to a peripheral mechanism.…”

Clinical Heterogeneity of Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome: A French Multicenter Retrospective Study

“…Totally, 90% of patients described herein had a positive anti-AIE75 kDa serology. Therefore, we find it to be a useful tool for the preliminary screening of patients that may possibly distinguish between IPEX syndrome and other immune deficiencies, such as autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy 19 . In our experience, severity and evolution of the disease do not correlate with the titre of anti-AIE75 kDa.…”

Specificity of antinuclear autoantibodies recognizing the dense fine speckled nuclear pattern: Preferential targeting of DFS70/LEDGFp75 over its interacting partner MeCP2

“…Although recent advances on the functional analysis of DFS70/LEDGFp75 have shed some light into its multiple molecular and cellular roles, the clinical and biological significance of its cognate autoantibodies still remains an enigma [9,41,57]. Whereas most cell-derived autoantigens are targeted preferentially by autoantibodies associated with specific organ-specific or systemic autoimmune diseases [1,58-60], and even in certain cancer types [61], to date DFS70/LEDGFp75 remains as an autoantigen without a specific clinical association [9]. …”

“…Careful analysis of such sera will help determine if they contain autoantibodies that target a conformational epitope of DFS70/LEDGFp75 that is lost in the detection assays, or other yet to be identified proteins associated with nuclear complexes in which this autoantigen is naturally found. Given that the clinical associations of anti-DFS70/LEDGFp75 autoantibodies are multiple and involve autoimmune, inflammatory, and malignant conditions [9], it would be also important to distinguish them, using different approaches, from other autoantibodies that specifically target antigens of 75 kD such as those targeting autoimmune enteropathy-related 75 kD antigen (AIE-75) in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) [58]. We anticipate that as our basic understanding of the anti-DFS70/LEDGFp75 autoantibody response increases, its clinico-biological significance will unravel, leading to translational applications.…”