(059) Autoimmune disease and the musculoskeletal system Flashcards
How can leukocytic tolerance be broken ?
• Microbial/Self antigen cross-reaction (molecular mimicry)
• Pathogen alters structure or presentation of self antigen
• Regulatory T cell failure
• Cytokine dis regulation
• Thymic defect
Rheumatoid arthritis prevalence ?
common (1% of population)
cytokines related to RA ?
-TNF alpha
- IL-1
-IL-6
….. is a protein that can be altered to contain citrulline residues during inflammation
vimentin
“During inflammation, arginine amino acid residues can be enzymatically converted into citrulline residues in proteins such as vimentin”
This process is called :
citrullination
…… have proved to be powerful biomarkers (highly specific) that allow the diagnosis of rheumatoid arthritis (RA) to be made at a very early stage.
Anti-citrullinated protein antibodies (ACPAs)
TNF Alpha activates ….. (Cells) in RA , leading to bone resorption
Osteoclasts (bone macrophages)
TNF Alpha leads to leukocyte accumulation at site of RA through the process of :
Upregulating E-selectin and VCAM-1 (Vascular Cell Adhesion protein 1)
Chondrocytes are activated by the action of ….. (Immune mediator)
TNF Alpha
…. (Immune mediator) is responsible for the extensive angiogenesis in RA
TNF Alpha
Diagnosis of RA by Blood tests ?
- CBC : Elevated erythrocyte sedimentation rate (ESR) or C-reactiVe protein (CRP) ; indicating inflammation
- Rheumatoid factor ,, and cyclic citrullinated peptide (anti-CCP) antibodies.
Imaging diagnosis of RA ?
- X-rays to help track the progression of rheumatoid arthritis in your joints over time.
- MRI and ultrasound tests can help in early diagnosis of inflammation and to detect severity of the disease in your body.
List methods of treating RA
1- Nonsteroidal anti-inflammatory drugs (NSAIDs)
2- Steroids
3- Disease-modifying antirheumatic drugs (DMARDs)
4- Biologic agents
Role of NSAIDs in RA treatment ?
relieve pain and reduce inflammation
Role of Steroids in RA treatment ?
And give an example
- reduce inflammation and pain and slow joint damage
- Example : prednisone
Side effects of steroidal treatment of RA ?
Side effects may include thinning of bones, weight gain and diabetes
How are steroids often used in the treatment of RA ?
Doctors often prescribe a corticosteroid to relieve acute symptoms, with the goal of gradually tapering off the medication
Disease-modifying antirheumatic drugs (DMARDs) ?
These drugs can slow the progression of rheumatoid arthritis and save the joints and other tissues from permanent damage.
Common DMARDs include methotrexate, hydroxychloroquine (Plaquenil) and sulfasalazine (Salazopyrine)
Famous synthetic DMARDs ?
-methotrexate
-hydroxychloroquine (Plaquenil)
-sulfasalazine (Salazopyrine)
Biological DMARDs that inhibit TNF-Alpha ?
-Infliximab
-Etanercept
-Adalimumab
Biological DMARDs that inhibit IL-1 ?
Anakinra
Biological DMARDs that inhibit IL-6 ?
Tocilizumab
Biological DMARDs that inhibit B Cell depletion ?
Rituximab
Biological DMARDs that inhibit co-stimulation?
Abatacept
Prevalence of Polymyositis/dermatomyositis ?
Fairly rare (prevalence 1 in 20,000)
What is Polymyositis/dermatomyositis ?
Muscle disease associated with inflammation and autoantibodies to histidyl-tRNA synthetase
the auto-antigen of Polymyositis/dermatomyositis ?
histidyl-tRNA synthetase
In polymyositis ; associated skin involvement occurs in …..% of cases
50-60%
This a microscopy of polymyositis : explain the found abnormality
Describe the microscopical abnormality ,, and give your diagnosis
Treatment options in polymyositis/dermatomyositis ?
-Corticosteroids
- synthetic DMARDs (Methotrexate)
- Azathioprine
- Intravenous immunoglobulin
Commonest treatment for MG ?
Acetylcholinesterase inhibitors
