Methods for the diagnosis and treatment of sjögren's syndrome
Described herein is the finding that patients with Sjögren's syndrome exhibit a statistically significant increase in expression of BMP6 in the salivary gland, relative to healthy control subjects. Also described herein is the finding that overexpression of BMP6 in the salivary glands of mice results in an increase in electrical potential across the salivary gland. Thus, provided herein are methods of diagnosing a subject as having Sjögren's syndrome, or at risk for developing Sjögren's syndrome, by measuring the level of BMP6 expression in a salivary gland of a subject, measuring electrical potential in a salivary gland of a subject, or both. Also provided herein are methods of treating a subject with Sjögren's syndrome by administering an agent that inhibits expression of BMP6 expression or activity. Also described herein is the use of XIST and MECP2 as diagnostic and therapeutic targets for male Sjögren's syndrome patients.
1. A method, comprising:
obtaining a biological sample from a human or mouse subject who has symptoms of dry eyes and/or dry mouth, wherein the biological sample is a salivary gland sample, a saliva sample or a serum sample;
detecting expression of bone morphogenic protein 6 (BMP6) in the biological sample of the human or mouse subject;
diagnosing the subject as having Sjögren's syndrome by (i) detecting at least a 2-fold increase in expression of BMP6 in the biological sample of the human or mouse subject relative to expression of BMP6 in a corresponding biological sample from a healthy control human or mouse subject, respectively, who does not have Sjögren's syndrome, and (ii) detecting the presence of autoantibodies to Ro (SSA) or La (SSB) antigens in the serum of the human or mouse subject; and
treating Sjögren's syndrome in the subject by administering a therapeutically effective amount of a corticosteroid to the subject.
2. The method of claim 1 , wherein the salivary gland sample is a minor labial salivary gland, parotid gland or a submandibular gland.
3. The method of claim 1 , wherein the increase is at least 3-fold or at least 4-fold relative to the healthy control human or mouse subject.
4. The method of claim 1 , wherein the biolgical sample is a salivary gland sample and detecting expression of BMP6 in the salivary gland sample comprises measuring the level of BMP6 mRNA in the salivary gland sample.
5. The method of claim 1 , wherein detecting expression of BMP6 in the biological sample comprises measuring the level of BMP6 protein in the biological sample.
6. The method of claim 1 , wherein the corticosteroid is cortisol or prednisone.
7. The method of claim 4 , wherein the level of BMP6 mRNA in the salivary gland sample is measured using RT-PCR.
8. The method of claim 5 , wherein the level of BMP6 protein in the salivary gland sample is measured using an immunoassay.
9. The method of claim 8 , wherein the immunoassay is an enzyme-linked immunosorbent assay (ELISA), an immunohistochemistry (IHC) assay, or a Western blot.
10. The method of claim 1 , wherein the subject is a human.
11. The method of claim 1 , wherein the subject is a mouse.
12. The method of claim 1 , wherein the biological sample is a salivary gland sample.
13. The method of claim 1 , wherein the biological sample is a saliva sample.
14. The method of claim 1 , wherein the biological sample is a serum sample.