LECTURE 4 - finished Flashcards
Where is the Human Leukocyte Gene located?
On the short arm of chromosome 6
What is the major histocompatibility complex (MHC) also known as?
The human leukocyte antigen complex (HLA)
What do HLA genes code for?
HLA proteins
What do HLA proteins do?
They are antigens. They become embedded in the cell membrane of all nucleated cells and platelets.
What is the function of HLA?
To enable the immune system to recognise its own cells by displaying self proteins.
To bind and display antigens from pathogens for recognition by T-Cells
HLA-B27 positive individuals are (??) times more susceptible to developing AS compared to the general
population
Approx 87x
What % of the normal population are HLA-B27 +ve?
3%-7%
What are the most common HLA-B27 syndromes?
Commonly when im Hungry, i eat A PEAR
Seronegative spondyloarthropathies (SpA):
– Psoriatic arthritis (50–60%)
– Enteropathic/Inflammatory bowel disease & spondylitis (50-60%)
– Ankylosing spondylitis (80-90% of patients)
– Reactive arthritis (60–90% of patients)
= PEAR
Acute anterior uveitis (50-60% of patients)
What are the indications to test HLA-B27?
Hungriness indicates we have to PEA
To provide supportive evidence for the dx of one of the HLA-B27 Syndromes in patients presenting with acute or chronic pain and inflammation of the:
• peripheral joints
• axial skeleton
• eyes
Define Myopathy
“any abnormality or disease of muscle tissue“
List some tests that might be conducted to diagnose myopathy
HAEMIE
- Hormone tests
- Antibody tests (e.g. MG & Muscle Dystrophy)
- Enzyme tests
- Muscle biopsy
- Inflammatory markers
- Electromyography (differentiates between myopathy & neurogenic processes)
- Urine haemoglobin tests (for myoglobin)
What are some indications to myopathy testing? (3)
General rule for indications:
- test those with family Hx
- diagnose condition
- monitor prediagnosed disease
• a family history of inheritable myopathy • complaining of undiagnosed muscle: − weakness − pain (often after exercise) − tenderness − fatigue − atrophy
• monitor the course and response to therapy of certain myopathies
Where is creatine kinase located?
On the inner mitochondrial membrane, on myofibrils, and in the muscle cytoplasm
What is creatine kinase involved in? When are increased creatine kinase serum levels seen?
Cellular energy storage and transfer
Increased levels seen in muscle injury
List the various forms of CK and where they are located (3)
- CK-1 (CK-BB): mostly in the CNS & lungs
- CK-2 (CK-MB): mostly in the heart
- CPK-3 (CK-MM): mostly in skeletal muscle
List a few causes of increase creatine kinase in the serum
CK increases CRRMMMSSS
Elevated CPK-3 levels usually indicates muscle injury or muscle stress: • Crush injuries • Rhabdomyolysis due to drugs or prolonged immobility • Recent electromyography • Muscular dystrophy • Myositis • Multiple intramuscular injections • Seizures • Surgery • Strenuous exercise etc.
Where is myoglobin found?
Skeletal and cardiac muscle
What are the usual tests for myoglobin?
Blood and urine
What usually causes increase myoglobin levels?
Myoglobin is increased when muscle is MASSED
Increased levels can occur in situations where muscle has been damaged:
• Muscle injections
• Accidents
• Seizures
• Surgery
• Exercise thats strenuous
• Disease of muscle(e.g. muscular dystrophy) of muscle
Indications for myoglobin testing:
URINE TEST: extensive skeletal muscle injury.
BLOOD TEST: Rapid breakdown of muscle releases myoglobin into the blood from where it can cause renal damage.
The test can be used to aid in the diagnosis of hereditary myopathies.
What are the 2 classes of antibody associated with the presence of idiopathic inflammatory myopathies (PMDM)?
Two classes of antibody are associated with the presence of the idiopathic inflammatory myopathies (IIMs) DM and PM:
• myositis-specific autoantibodies (MSA)
• myositis-associated autoantibodies (MAA)
What are myositis-specific autoantibodies (MSA)? What do they target?
Definition: A group of autoantibodies that appear in sufferers of autoimmune myositis.
MSAs typically target nuclear or cytoplasmic components involved in gene transcription, protein translocation & anti-viral responses
What are myositis-associated autoantibodies?
Definition: A group of autoantibodies appearing in patients with autoimmune overlap syndromes (i.e. combinations of PM, DM, and other autoimmune diseases e.g.
- PM-Scl 100 / 75 antibodies: found in 50-70% of patients diagnosed with a combination of PM/DM & SSc
- Ku antibodies: seen in 25% of patients with polymyositis-scleroderma overlap syndrome
Indications for muscle biopsy?
- Duchenne muscular dystrophy (DMD)
- Becker muscular dystrophy
- Myasthenia gravis (MG)
- Polymyositis
- Dermatomyositis
- Amyotrophic lateral sclerosis (ALS)
What are some skin lesions?
- Progressive systemic sclerosis
- Systemic lupus erythematosus
- Dermatomysositis
Indications for skin biopsies?
Skin biopsies are mainly used to aid the diagnosis of:
• Progressive systemic sclerosis
• Systemic lupus erythematosus (immune complex deposition at the epidermal-dermal junction)
• Dermatomysositis
