Context: Role of parathyroid autoimmunity in idiopathic hypoparathyroidism (IH) is not clear. Recently, parathyroid-specific NACHT leucine-rich-repeat protein 5 (NALP5) autoantibodies (Ab) have been reported in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.
Objective: Our objective was to assess prevalence and significance of NALP5 Ab in patients with IH.
Design and setting: This was a case-control study at a tertiary care hospital.
Subjects: Subjects included 145 patients with IH recruited from 1998-2011 and 152 healthy controls.
Methods: Immunoprecipitation (IP) and Western blot (WB) assays were performed using ³⁵S-labeled NALP5 protein produced by in vitro transcription-translation and recombinant NALP5 protein in Escherichia coli, respectively. AIRE gene sequencing was performed in NALP5 Ab-positive patients.
Results: One of 145 patients (0.69%) and none of the 152 controls had NALP5 Ab on IP assay. Nine of 147 patients (6.12%) and four of 152 controls (2.63%) had NALP5 Ab on WB. One patient with NALP5 Ab on IP (36.6 sd score), also positive on WB, had a frameshift p.Ala386Serfs*38 AIRE gene mutation and adrenocortical Ab. Eight subjects with NALP5 Ab detected on WB had normal AIRE gene sequence.
Conclusions: IP is currently the best assay to detect clinically relevant NALP5 Ab. Presence of NALP5 Ab in only one patient with IH who also had AIRE gene mutation suggests that these Ab are exceptionally rare in IH (0.69%) and, when present, occur in context of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.