Rheumatoid arthritis pathophysiology: Difference between revisions
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===Pathogenesis=== | ===Pathogenesis=== | ||
[[Rheumatoid arthritis]] is mediated by the combination of a predisposing genotype upon which genetic factors, environmental and microorganism also contribute resulting in the | [[Rheumatoid arthritis]] is mediated by the combination of a predisposing genotype upon which genetic factors, environmental and microorganism also contribute resulting in the inflammation and destruction of the synovial membrane. | ||
'''Various factors involved are''' | |||
'''Environmental factors''': It causes repeated activation of innate immunity at mucosal surfaces. | '''Environmental factors''': It causes repeated activation of innate immunity at mucosal surfaces. | ||
*Smoking interacts with genes to increase susceptibility up to 20- to 40-fold. | *Smoking interacts with genes to increase susceptibility up to 20- to 40-fold. | ||
Revision as of 19:29, 9 April 2018
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]
Overview
Pathophysiology
Pathogenesis
Rheumatoid arthritis is mediated by the combination of a predisposing genotype upon which genetic factors, environmental and microorganism also contribute resulting in the inflammation and destruction of the synovial membrane. Various factors involved are Environmental factors: It causes repeated activation of innate immunity at mucosal surfaces.
- Smoking interacts with genes to increase susceptibility up to 20- to 40-fold.
Microrganism:
- In periodontal disease, P. gingivalis is commonly found, it also expresses peptidyl arginine deiminases.
- This can lead to citrullination and thereby promote ACPA.
- A. actinomycetemcomitans produces a toxin that increases calcium influx into neutrophils which further lead to citrullination of peptides and promote APCA.
Genetic factors:
- Genetics factors like class II major histocompatibility complex (MHC), most common human leukocyte antigen (HLA)-DR.
- These genes are involved in implicating immune response, matrix regulation, and inflammation.[3]
Immunologic response
- All the above factors lead to citrullination or post-translational modifications, the altered peptides bind to MHC protein with shared epitopes which further lead to antigen presentation to T-cells.
- T cells further stimulate B cells to produce a range of antibodies that recognize self-proteins, including Rheumatoid factors and ACPAs (targeting citrullinated proteins).
- Fibroblast-like synoviocytes, APCs, and macrophages are activated locally and produce various inflammatory factors.
- The autoimmune response causes synovial inflammation and there is the formation of an immune complex formation and complement activation, leading to an increase in cytokine production and synovial vascular leakage.
- Cytokine leads to bone and cartilage destruction.
Genetics
- [Disease name] is transmitted in [mode of genetic transmission] pattern.
- Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
- The development of [disease name] is the result of multiple genetic mutations.
Associated Conditions
Gross Pathology
On gross pathology of rheumatoid arthritis:[4]
- Pannus formation which is made up of fibrovascular tissue or granulation tissue.
- The irregular surface is due to synovial hyperplasia.
- Subchondral cysts usually present at the later stage of the disease.
Microscopic Pathology
- On microscopic histopathological analysis:
- On the earliest findings is the formation of the new synovial blood vessel.
- In response to TNF cytokines are produced.
References
- ↑ Lundström E, Källberg H, Alfredsson L, Klareskog L, Padyukov L (June 2009). "Gene-environment interaction between the DRB1 shared epitope and smoking in the risk of anti-citrullinated protein antibody-positive rheumatoid arthritis: all alleles are important". Arthritis Rheum. 60 (6): 1597–603. doi:10.1002/art.24572. PMC 2732897. PMID 19479873.
- ↑ Makrygiannakis D, Hermansson M, Ulfgren AK, Nicholas AP, Zendman AJ, Eklund A, Grunewald J, Skold CM, Klareskog L, Catrina AI (October 2008). "Smoking increases peptidyl arginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells". Ann. Rheum. Dis. 67 (10): 1488–92. doi:10.1136/ard.2007.075192. PMID 18413445.
- ↑ Bottini N, Firestein GS (November 2013). "Epigenetics in rheumatoid arthritis: a primer for rheumatologists". Curr Rheumatol Rep. 15 (11): 372. doi:10.1007/s11926-013-0372-9. PMID 24072602.
- ↑ Resnick D, Niwayama G, Coutts RD (May 1977). "Subchondral cysts (geodes) in arthritic disorders: pathologic and radiographic appearance of the hip joint". AJR Am J Roentgenol. 128 (5): 799–806. doi:10.2214/ajr.128.5.799. PMID 404905.