CLINICAL ANALYSIS OF THE COMPLEX WORLD OF INHERITED MULTIPLE AUTOIMMUNITY

IPEX is characterized by early-onset severe autoimmune enteropathy, eczema and endocrinopathy. Increasing number of patients affected by multiple autoimmunity resembling IPEX, without FOXP3 mutations have contributed to define an IPEX-like phenotype. We set to identify clinical and laboratory indicators to better define this disease spectrum. Clinical characteristics of about 76 patients with immunodysregulation referred to us for suspected IPEX syndrome were analyzed: only 16 had FOXP3 mutations and in selected patients STAT5b, CD25, STAT1 and IL10 deficiency (IL10RA, IL10RB, IL10) have been ruled out. Immune mediated enteropathy, frequently associated with failure to thrive, was the key clinical feature. In patients without enteropathy, endocrinopathy and cytopenias are the main clinical manifestations. The age of onset is diverse: a group of patients presents diarrhoea within the first year of life and behave similarly to the IPEX cohort, another group had a delayed onset characterized by multiple autoimmune disease (skin and endocrinopathy being less predominant than to autoimmune cytopenias and infections), whilst a third group had only early onset diarrhoea with no other symptoms associated (IBD-like?). Elevated IgE and dysgammaglobulinemia are often reported. Outputs from this study define disease subgroups facilitating precise molecular studies in order to better understand and delineate the mechanisms of tolerance failure in patients with complex autoimmune disease. The final objectives would be definition of new disease entities and ultimately discovery of new genes involved in immune-dysregulation diseases.