Risk Factors and Diagnosis of RA Flashcards
Recall the principle of all autoimmune disease.
Recall the risk factors for RA.
Recall regarding the HLA genetic risk factors of RA.
HLA complex is located on chromosome ___.
Location and organisation of HLA complex on chromosome 6.
Recall the significance of “shared epitope”.
HLA-DRB1 alleles that confer RA risk encode (share) a five amino acid sequence termed ‘shared epitope’: QKRAA
- occupies position 70 to 74 of the HLA-DR ß chain
- surrounds peptide-binding groove (determines antigen-binding specificity and presentation to CD4+ T helper cells)
- postulated this portion of the DRB1 molecule may control susceptibility to disease
May predict RA severity
- increase joint damage
- prevalence extra-articular manifestations
Shared epitope is strongly related to expression of _________________.
Shared epitope is strongly related to the expression of anti-citrullinated protein antibody (ACPA/anti-CCP)
- Associated only with ACPA-positive disease
Describe citrullination.
It is the post-transcriptional conversion of the amino acid arginine to citrulline by peptidyl-arginine deiminase (PADI) enzymes.
- Role of citrullination in RA risk:
- Neoepitopes serve as targets for autoimmunity
- Citrulline binds shared epitope more avidly
- Immune tolerance breakdown - ACPA (Anti-CCP)
Note: induction of PADI expression and peptide citrullination is not specific to joint or RA and occurs in many different settings of tissue stress/inflammation
Human has _____ isoforms of PADI. ________ and ____________ are abundant in inflamed synovial fluid and tissue in RA.
4
PADI2 and PADI4
________ catalyze the hydrolytic deimination of peptidyl arginine to peptidyl citrulline and ammonia.
Peptidyl arginine deiminase (PAD)
Recall the concept of the odds ratio.
Recall Non-HLA genetic risk factors for RA.
Recall epigenetic mechanism.
Recall the epigenetic mechanisms in RA.
Explain the female preponderance in RA.
Recall the mechanism of protection against RA during pregnancy.
Recall environmental risk factors of RA.
Recall the microbiome emerging theory of RA.
Recall the neurological emergency theory of RA.
Mention the autoantibodies present in RA.
Recall the concept of test sensitivity and specificity
What is positive likelihood ratio?
What is negative likelihood ratio?
Recall the diagnostic utility of autoantibodies in RA
Recall about seropositivity of RA.
Recall the 2010 ACR/EULAR Classification Criteria for RA.
- Patients to be tested must be newly presenting patients who have
- >= 1 joint with definite clinical synovitis (swelling)
- Synovitis not better explained by another disease
Recall the assessment of RA disease activity.
Recall the DAS28 cutoff criteria.
