Novel neuronal and endocrine autoantibody targets in autoimmune polyendocrine syndrome type 1

Abstract

Context. Although pituitary autoantibodies have frequently been reported in Autoimmune Polyendocrine Syndrome type 1 (APS1), the autoimmune involvement of the hypothalamic-pituitary axis remains to be elucidated. Objective. Our aim was to identify in APS1 patients novel autoantibodies, especially against hypothalamic-pituitary targets, and to correlate their presence with clinical features. Patients. We analyzed 14 APS1 patients from Sardinia, compared to other diseases and healthy donors. Measure(s). We used immunohistochemistry, on tissues substrates from various neuroendocrine organs, to detect autoantibody targets. Immunoenzymatic assays, as well as absorption with specific antigens were used to reveal autoantibodies against growth hormone (GH), luteinizing hormone (LH) and somatocrinin (GHRH). Clinical evaluations included GH secretory and cardiovascular autonomic neuropathy tests. Results. Sera from 12/14 APS1 patients revealed autoantibodies reacting with the hypothalamic-pituitary axis, cerebellum, substantia nigra, and/or adrenal medulla, as well as with GH, LH and/or GHRH. Of APS1 patients, 5 showed GH deficiency, in association (4/5 cases) with autoantibodies to hypothalamic and/or pituitary targets. Hypogonadotrophic hypogonadism was revealed in one APS1 patient, together with autoantibodies against gonadotropes. Autonomic neuropathy was detected in 5 of 10 patients, associated with autoantibodies to adrenal medulla in 2 cases. Of 5 patients with autoantibodies to cerebellar neurons, 2 reported emotional or memory alterations. Conclusions. The majority of Sardinian APS1 patients developed autoantibodies to an assortment of neuroendocrine cells. Novel targets of clinical relevance may include pituitary hormones, uncharacterized pituitary targets, and adrenal medullary cells. An high prevalence of GH deficiency, and possibly of autonomic neuropathy, were also revealed.

Keywords::

• Autoimmune Polyendocrine Syndrome
• autoantibodies
• GHRH neurons
• pituitary hormones
• adrenal medulla

Acknowledgements

We are grateful to all patients and control subjects, who made this study possible. G. Boi, F. Incollu and the COALBE Company are thanked for bovine tissue samples. Supported by grants from Italian MIUR-PRIN (#2002067915_002 to GLF, #2002067915_001 to SM) and by the TABA project of the University of Trieste (to ET). The National Institute of Diabetes and Digestive and Kidney Diseases – NIDDK, the National Hormone and Pituitary Program, and the Developmental Studies Hybridoma Bank, University of Iowa, Iowa City, USA are acknowledged for the supply of purified hormones and antibodies. The authors have nothing to declare.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.)