Methods for the diagnosis and treatment of sjögren's syndrome

Inventors

Chiorini, John A.

Assignees

US Department of Health and Human Services

Publication Number

US-9833519-B2

Publication Date

2017-12-05

Expiration Date

2033-09-25

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Abstract

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.

Core Innovation

Patients with Sjögren's syndrome exhibit a statistically significant increase in expression of bone morphogenetic protein 6 (BMP6) in the salivary gland compared to healthy control subjects. Overexpression of BMP6 in the salivary glands of mice results in an increase in electrical potential across the salivary gland and leads to loss of salivary gland activity.

The invention provides methods of diagnosing a subject as having Sjögren's syndrome, or being at risk for developing it, by measuring the level of BMP6 expression in a biological sample (such as salivary gland tissue) or by measuring electrical potential or impedance in the salivary gland. Increased BMP6 expression or electrical potential relative to controls indicates the presence or risk of Sjögren's syndrome.

Additionally, methods of treating Sjögren's syndrome include administering an agent that inhibits the expression or activity of BMP6. The invention also describes diagnostic and therapeutic targets for male Sjögren's syndrome patients involving expression of XIST and MECP2, where males with Sjögren's syndrome aberrantly express XIST and down-regulate MECP2.

Claims Coverage

The patent contains one independent claim focused on a method for diagnosing and treating Sjögren's syndrome.

Method for diagnosing Sjögren's syndrome by detecting BMP6 expression and autoantibodies

Obtaining a biological sample (salivary gland, saliva, or serum) from a subject with dry eyes and/or dry mouth symptoms; detecting at least a 2-fold increase in BMP6 expression relative to a healthy control; detecting presence of autoantibodies to Ro (SSA) or La (SSB) in serum; diagnosing the subject with Sjögren's syndrome based on these criteria.

Method for treating Sjögren's syndrome by administering corticosteroids

Treating the diagnosed subject by administering a therapeutically effective amount of corticosteroids such as cortisol or prednisone.

The claims cover a diagnostic method involving measurement of BMP6 expression and autoantibodies for detecting Sjögren's syndrome and treatment of the disease by corticosteroid administration.

Stated Advantages

The diagnostic methods provide an objective, reproducible standard for diagnosing Sjögren's syndrome without relying exclusively on subjective criteria.

The treatment methods offer targeted therapeutic intervention by inhibiting BMP6 expression or activity, potentially improving salivary gland function.

Documented Applications

Diagnosis of Sjögren's syndrome by detecting BMP6 expression levels in biological samples such as salivary gland biopsy, saliva, or serum.

Diagnosis of Sjögren's syndrome by measuring electrical potential or impedance in the salivary gland.

Treatment of Sjögren's syndrome by administering agents that inhibit BMP6 expression or activity, corticosteroids, immunosuppressive drugs, or non-steroidal anti-inflammatory drugs.

Use of XIST and MECP2 expression levels as diagnostic and therapeutic targets specifically in male Sjögren's syndrome patients.

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