LECTURE 4 - finished

Question 1

Where is the Human Leukocyte Gene located?

Answer 1

On the short arm of chromosome 6

Question 2

What is the major histocompatibility complex (MHC) also known as?

Answer 2

The human leukocyte antigen complex (HLA)

Question 3

What do HLA genes code for?

Answer 3

HLA proteins

Question 4

What do HLA proteins do?

Answer 4

They are antigens. They become embedded in the cell membrane of all nucleated cells and platelets.

Question 5

What is the function of HLA?

Answer 5

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

Question 6

HLA-B27 positive individuals are (??) times more susceptible to developing AS compared to the general
population

Answer 6

Approx 87x

Question 7

What % of the normal population are HLA-B27 +ve?

Answer 7

3%-7%

Question 8

What are the most common HLA-B27 syndromes?

Answer 8

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)

Question 9

What are the indications to test HLA-B27?

Answer 9

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

Question 10

Define Myopathy

Answer 10

“any abnormality or disease of muscle tissue“

Question 11

List some tests that might be conducted to diagnose myopathy

Answer 11

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)

Question 12

What are some indications to myopathy testing? (3)

Answer 12

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

Question 13

Where is creatine kinase located?

Answer 13

On the inner mitochondrial membrane, on myofibrils, and in the muscle cytoplasm

Question 14

What is creatine kinase involved in? When are increased creatine kinase serum levels seen?

Answer 14

Cellular energy storage and transfer

Increased levels seen in muscle injury

Question 15

List the various forms of CK and where they are located (3)

Answer 15

• 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

Question 16

List a few causes of increase creatine kinase in the serum

Answer 16

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.

Question 17

Where is myoglobin found?

Answer 17

Skeletal and cardiac muscle

Question 18

What are the usual tests for myoglobin?

Answer 18

Blood and urine

Question 19

What usually causes increase myoglobin levels?

Answer 19

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

Question 20

Indications for myoglobin testing:

Answer 20

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.

Question 21

What are the 2 classes of antibody associated with the presence of idiopathic inflammatory myopathies (PMDM)?

Answer 21

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)

Question 22

What are myositis-specific autoantibodies (MSA)? What do they target?

Answer 22

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

Question 23

What are myositis-associated autoantibodies?

Answer 23

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

Question 24

Indications for muscle biopsy?

Answer 24

• Duchenne muscular dystrophy (DMD)
• Becker muscular dystrophy
• Myasthenia gravis (MG)
• Polymyositis
• Dermatomyositis
• Amyotrophic lateral sclerosis (ALS)

Question 25

What are some skin lesions?

Answer 25

• Progressive systemic sclerosis
• Systemic lupus erythematosus
• Dermatomysositis

Question 26

Indications for skin biopsies?

Answer 26

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