In addition to the local exocrine gland pathology, patients with SS have alterations in the neuroendocrine system including the hypothalamus-pituitary-adrenal axis (HPA), the hypothalamic-pituitary-gonadal axis and the autonomic nervous system.[56] The HPA and autonomic nervous systems modulate local and systemic immune responses through nicotinic receptors in the brain, while non-neuronal nicotinic acetylcholine and cholinergic receptors in the periphery have been shown to modulate the Th17 response in CD4+ T lymphocytes[57]. This evidence concerns the gene CD4 and synovial sarcoma.