Notes lectures Minor Clinical Immunology Rheumatology theme
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Course
Rheumatology (G3M011)
Institution
Universiteit Leiden (UL)
Notes of all lectures belonging to the Rheumatology theme of the Minor Clinical Immunology (LUMC Half minor). Titles of lectures given are:
- New insights in pathophysiology – systemic sclerosis (SSc)
- Axial spondyloarthritis
- Systemic lupus erythematosus
- Rheumatoid arthritis
Lm slot, jk vries - bouwstra, fa van gaalen, d van der woude, rem toes
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Subjects
rheumatology
sle
lupus
spa
spondyloarthritis
ssc
systemic sclerosis
rheumatoid arthritis
antibodies
ana
systemic lupus erythromatosus
ra
Written for
Universiteit Leiden (UL)
Minor Clinical Immunology
Rheumatology (G3M011)
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LT New insights in pathophysiology – systemic sclerosis
(SSc)
Women are more often affected by SSc than man; it often develops at the age of 30-50 year
Genetic, epigenetic and environmental factors lead to vascular abnormalities and
immunologic abnormalities which lead to extracellular membrane abnormalities (fibrosis)
Variants in HLA are associated with a higher risk of SSc (but it’s still a very rare disease)
It’s an autoimmune disease; different subtypes of the disease have different types of
antibodies
The disease is very heterogeneous; all organs can be affected
Subtypes of SSc are limited cutaneous SSc and diffuse cutaneous SSc; the distinguishment is
based on the skin involvement limited has only involvement of the distal parts of the
body, diffuse also has involvement of the trunk; each type has different clinical features
(different organs are involved)
Antibodies involved in SSc are often ANAs, they attack vascular endothelium cells and
immunological cells; these cells have abnormalities leading to expression of antigens
recognized by the antibodies
Multiple antinuclear antibodies are associated with SSc; they are targeted against chromatin
proteins, RNA polymerase, RNase, exosome proteins, etc.
The clinical picture depends on the antibody which is present
Cytokines that are involved in extracellular matrix production by the fibroblasts are released
at higher levels causing more fibrosis
The first symptoms that often occur are the Reynaud’s phenomenon (white fingertips) and
digital ulcers; later, fibrosis will occur which will eventually result in skin atrophy and organ
changes
The patients have vascular damage which can be seen by looking at the nailfolds (have small
capillaries); they also have problems with wound healing; red spots on the skin are caused
by widened blood vessels, also present in the organs such as the stomach and kidneys
leading to bleeding and renal failure
Skin fibrosis is the most typical feature; it is scored by the modified Rodnan Skin Score
(mRSS)
Fibrosis also occurs within the lungs; it causes a decrease in total lung capacity
Treatments can target the vascular complications, fibrosis and/or the immune system
Treatment options:
- Vascular complications are treated with ACE inhibitors which prevent death in
patients with renal failure
- Fibrosis development may be inhibited a bit by targeting TGF- with an antibody;
another more promising target is VGEFR (earlier in the process) in patients with lung
involvement
- The immune system is targeted by biologicals such as Belatacept (blocks co-
stimulation in T-cell activation) and tocilizumab (anti IL-6, used to treat the lung
involvement); many drugs are used in other diseases and are now tested in SSc
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