Central immune tolerance of T and B cells in patients with idiopathic hypoparathyroidism, T1D and autoimmune thyroiditis.

Abstract Context: Pathogenesis of idiopathic hypoparathyroidism is under investigation. Abnormalities in central immune tolerance have yet not been investigated in them. T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs), formed during receptor gene rearrangements, is novel tools to assess central T- and B -cell output. Objective: We assessed the number of circulating TRECs and KRECs in patients with IH, autoimmune type-1 diabetes (T₁D), and thyroiditis (AT) and healthy controls (HC). <b> </b> <b>Design: </b>Comparative case-control at tertiary care center.<b> </b> <b> </b> <b>Subjects and methods: </b>Absolute and relative TRECs and KRECs were measured in DNA extracted from whole blood of IH patients (n = 181, 22 of whom were reassessed after a decade of follow-up), T₁D (n = 133), AT (n = 53), and HC (n = 135) using quantitative RT-PCR/TaqMan probe® technique. <b> </b> <b>Results: </b> Absolute and relative means of TRECs and KRECs in IH were comparable to HC and no differences were found between IH with and without CaSRAb or class I <i>HLA-A*26:01</i> association<i>. </i>TRECs and KRECs did not change after a decade of follow-up. T₁D had significantly higher absolute TRECs than IH, AT and HC, while AT patients showed lower TRECs and the highest KRECs; these levels showed no significant correlation with thyroid dysfunctions. <b> </b> <b>Conclusion:</b> Patients with IH showed TRECs and KRECs comparable to HC indicating an intact mechanism of T- and B-cell central immune tolerance. Interestingly, absolute TRECs were significantly higher in T₁D than HC, suggesting impaired central immune tolerance in T₁D.<br>