An historical approach to the genetic distribution of KIR and HLA ligands in Eastern Sicilians compared to modern descendants of their invaders.

A geographical stratification of Killer Immunoglobulin-like Receptors (KIR) has been reported worldwide. We first analyzed the distribution of 15 KIR genes in a sample of 50 East-Sicilians (ES). We used a Principal Component Analysis (PCA) to compare the KIR genetic content among ES and 10 modern populations who are descendants of the ancient invaders of Sicily: Spanish, French, Norwegians, Swedes, Finns, Tunisians, Moroccans, Arabs, Greeks, Turks. We also included a sample of Sardinians, and Senegalese (as outlier group). Then, we also compared the HLA-A, HLA-B and HLA-C allelic frequencies among ES and the same populations investigated for KIR. As to HLA-A and HLA-B polymorphisms, ES are close to Greek population who invaded the island for long time until 827 CE; while HLA-C and KIR distribution in ES are close to Spanish population that invaded Sicily (and Sardinia) starting from 1283. As to KIR, ES are close to Spanish and Sardinians. The immunogenetic fingerprint of ES may be the finely balanced result of the invasions that overwhelmed Sicily over the centuries.

Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α-lipoic acid.

OBJECTIVE: Lipoic acid (LA) is a widely used nutritional supplement and is sometimes used as an adjuvant treatment for diabetic neuropathy and other conditions. Insulin autoimmune syndrome (IAS, Hirata disease) is a rare cause of spontaneous hypoglycaemia, extremely high serum insulin levels and high titres of autoantibodies against endogenous insulin despite no prior exposure to exogenous insulin. In Japanese individuals, IAS is associated with the human leucocyte antigen (HLA) HLA-DRB1*04:06 allele and often occurs upon exposure to sulphhydryl-containing compounds including LA. Only one case has been reported in Caucasians. We now report six Caucasian patients taking LA with IAS and describe a unique HLA subtype in these patients. RESEARCH DESIGN AND METHODS: Six Caucasian patients (M = 3; F = 3), median age 63 years, presented with spontaneous episodes of fasting and postabsorptive hypoglycaemia associated with mainly neuroglycopenic symptoms. No patient was treated with insulin or had an insulinoma. Hypoglycaemic symptoms appeared 30 and 120 days after taking lipoic acid (LA; 600 mg/day). Case histories and standard laboratory analyses were utilized. RESULTS: Discontinuation of LA resulted in a reduction in hypoglycaemic episodes. All patients were treated with oral or iv glucose and prednisone (12.5-25 mg/day). HLA analysis revealed the HLA-DRB1*04:03 allele in five patients, while the HLA-DRB1*04:06 allele was present in one patient. CONCLUSIONS: This is the first report of LA-related IAS in Caucasians who possess the HLA-DRB1*04:03 allele, implicating this allele in the genetic susceptibility to IAS in Caucasians. The greater occurrence of the HLA-DRB1*04:03 allele in Caucasian and other populations, combined with the growing use of LA in developed countries, may be a future predictor of additional cases of IAS.