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).

Design: Comparative
case-control at tertiary care center.

Subjects and methods: 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.

Results: 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 HLA-A*26:01 association. 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.

Conclusion: 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.