USMLE® Step 1 style questions USMLE
A 43-year-old woman comes to the office because of dry mouth and eyes, which has persisted for four months. She has been experiencing fatigue and amenorrhea over the same period of time. Examination of the patient’s mouth shows multiple dental caries. Which of the following is the most likely pathophysiologic mechanism underlying her symptoms?
Contributors:Pauline Rowsome, BSc (Hons), Tanner Marshall, MS, Evan Debevec-McKenney, Jahnavi Narayanan, MBBS
Sjogren's syndrome, named after Dr. Henrik Sjogren who first identified it, is a common autoimmune disorder, typically occurring in women.
In Sjogren’s syndrome, the body’s immune cells go rogue and start attacking various exocrine glands, which are glands that pour their secretions into a duct; most commonly the salivary glands and the lacrimal, or tear, glands.
Pieces of the pathogen called antigens are then presented on a major histocompatibility complex class II molecule, or MHC-class II molecule - which is like a serving platter for antigens. An antigen presenting cell then searches for a T cell that can bind to the antigen.
Once found, binding to the antigen helps activate this T cell, which then releases proinflammatory cytokines, or signaling molecules, that recruit more immune cells - ultimately leading to inflammation.
The exact cause for Sjogren's syndrome is unknown, but it seems to be related to both genetic and environmental factors.
Genetic factors include genes which code for specific types of MHC class II molecules, called human leukocyte antigen, or HLA genes. Specifically HLA- DRW52, HLA- DQA1, or HLA- DQB1.
Environmental factors include an infection of exocrine glands like the salivary and lacrimal glands. Infections can damage the cells of the salivary gland, and expose their cell components, including their DNA, RNA, and histones to circulating immune cells.
These cell components get picked up by antigen-presenting cells, and presented to T-cells. In individuals with Sjogren's syndrome, a T cell gets inappropriately activated by these nuclear components, and considers them to be foreign nuclear antigens.
The T-cells then activate B-cells, which start producing anti-nuclear antibodies, or ANAs, which are antibodies against the nuclear antigens.
Two types of ANA formed in Sjogren’s syndrome are anti- SS-A and anti- SS-B antibodies, which are formed against the ribonucleoproteins SS-A and SS-B.
Then, both T-cells and antibodies enter the circulation and reach the exocrine glands, where the T-cells secrete cytokines to recruit more immune cells and promote inflammation of the exocrine gland tissue.
- "Robbins Basic Pathology" Elsevier (2017)
- "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
- "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
- "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
- "Update in Sjögren syndrome" Current Opinion in Rheumatology (2000)
- "Novel autoantibodies in Sjögren's syndrome: A comprehensive review" Autoimmunity Reviews (2019)
- "Sjögren's syndrome" The Lancet (2005)