Druggable monogenic immune defects hidden in diverse medical specialties: Focus on overlap syndromes

Liver kidney microsome antibodies. Analysis of a laboratory series

“…Narkewicz et al characterized 63 children with acute liver failure caused by AIH and found LKM antibodies in 15 of them (24%), 12 having LKM alone, 3 LKM and ANA, and 2 LKM and smooth muscle antibodies [ 6 ]. Muratori et al studied 21 patients with type 2 AIH and demonstrated that 7 of those were positive for LKM1 (33%), 9 for LC1 and 5 for both [ 13 ]. More recently, Khayat et al found LKM antibodies in 2 of 10 (20%) patients with autoimmune liver disease and 1 of 14 (7%) patients with autoimmune liver disease plus non-alcoholic fatty liver disease [ 9 ].…”

“…The disease is more commonly sporadic but given that AIH type 2 patients are typically children (in contrast to most autoimmune diseases), genetic causes have been investigated. Only a handful of autoimmune diseases are caused by a single gene defect [ 13 ], such as the autoimmune polyglandular syndrome type 1, caused by mutations in the AIRE gene [ 14 ]. This syndrome, characterized by the triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison disease, also features AIH type 2 in about a quarter of the cases [ [15] , [16] , [17] ].…”

Inborn Errors of Immunity in Children with Autoimmune and Allergic Complaints: A Single Center Experience from Diagnosis to Treatment

“…To this purpose, shared protocols are needed to improve patient selection among those presenting with immune dysregulation phenotypes to reach more effective selection criteria [3,4]. Some "red flags" have been proposed based on clinical experience, including multi-organ autoimmune/inflammatory involvement, lymphoproliferative manifestations, presentation in early childhood and refractoriness to conventional therapies [5]; nevertheless, patient selection for further immunological and genetic work-up is still largely at the physician's discretion.…”