Term
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Definition
| Also called "Myosites," IMMs are Heterogeneous group of Autoimmune syndromes characterized by muscle Weakness and striated muscle inflammation of Unknown cause |
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Term
| What epidemiological features define IIMs? |
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Definition
1) Rare- incidence: 5-10/million
prevalence: 50-90/million
2) Bimodal- age 5-15 and 30-50
3) Gender: Female > Male (2-3:1) |
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Term
| What are the 5 classifications for IM? |
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Definition
1) Adult Polymyosisitis (PM)
2) Adult Dermatomyositis (DM)
3) Juvenile Myositis (JDM>>JPM)
4) Myositis in overlap with other autoimmune illness/connective tissue disease
5) Myositis in overlap with malignancy. |
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Term
| What are the most common clinical features of myositis? |
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Definition
1) Proximal muscle weakness (neck/deltoid/bicep/psoas/quad)- Difficulty holding arms up, combing hair, getting out of a chair and walking
2) Skin rashes (Gottron's papules over fingers and MCP joints and Heliotropic rash over eyelids). See vasculitis and calcinosis in JDM.
3) Systemic- Fatigue/fever; arthritis; lung fibrosis; ILD; cardiac; GI |
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Term
| What immune molecules do inflamed muscle cells express in IIM? |
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Definition
Everything you need for antigen processing and presentation (need APC for co-stimulation), apoptosis and inflammation
1) MHC-II molecules and relevant proteases for processing and presentation
2) Class 1 antigens
3) Ligands for T-cell interaction
4) Surface Fas receptor-apoptosis
5) Pro-inflammatory cytokines |
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Term
| How does antigen processing and presentation occur in IIM? |
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Definition
| Muscle cell processes and presents class I and class II antigens to T cells, but probably needs B7-signal 2 from APCs for co-stimulation and T-cell activation. |
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Term
| How can you distinguish PM from DM in adults? |
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Definition
1) Polymyosites = MYOFIBER
-CTL invasion of non-necrotic muscle fiber
-Perimysial/perivascular CD4+ T helper infiltrates
- Inflammatory infiltrate WITHIN fascicle
- Scattered necrotic fibers
2) Dermatomyositis= BLOOD VESSEL
- perivascular B cells and C5-C9
- endomysial CTLs
- perimysial CD4+ T cells
- perivascular infiltrate AROUND FASCICLE
- groups of necrotic fibers
- perifascular atrophy (90% of children) |
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Term
| Describe the basic autoimmune pathogenesis of IIM. |
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Definition
Common to PM, DM, thyroiditis and Sjogren's
1) Virally-damaged muscle liberates auto-antigenic aminocacyl-tRNA synthetases (RS)
2) RS recuit mononuclear cells that induce innate and adaptive IR and lead to the perpetuation of myositis
3) Autoantibody response against RS such as Jo-1 (HisRS) leads to autoimmunity. |
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Term
| What are the basic cellular and humoral components of the immune response to IIM? |
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Definition
1) Cellular-
- muscle and peripheral T and B cells bearing activation markers
- cytokines
- increased peripheral mononuclear trafficking to muscle
2) Humoral-
- circulating immune complexes
-Ig and complement deposition in vascular endothelium of muscle (DM),
- Autoantibodies (nonspecific-ANA, anti-thyroid, myositis-associated and myositis-specific- anti-Jo-1 |
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Term
| What is the relevance of Jo-1 in IIM? |
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Definition
Jo-1 is a Histidyl tRNA synthetase that is thought to have pro-inflammatory properties following viral damage to muscle cells.
Anti-Jo-1 antibody develops to prevent inflammation and in doing so, prevents protein synthesis |
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Term
| What is the importance of tRNA synthetases in the pathogenesis of IIM? |
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Definition
TyrRS (cytokine homology) AsnRS have pro-inflammatory effects by recruiting mononuclear cells to sites of muscle inflammation.
**During apoptosis, TyrRS is cleaved to Monocyte Activator and IL-8-like cytokine** |
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Term
| What bridges the adaptive and innate immune system responses to IIM? |
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Definition
1) Type 1 IFNs are induced in DM and PM (probably by recruited mononuclear cells communicating with T-cells).
2) IFN-inducible protein (MxA) is present in DM muscle (downstream support)
** similar toIFN "signature" seen in SLE** |
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