Rheumatoid arthritis pathophysiology: Difference between revisions
| Line 51: | Line 51: | ||
*T cells further stimulate B cells to produce a range of antibodies that recognize self-proteins, including Rheumatoid factors and ACPAs (targeting citrullinated proteins). | *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. | *Fibroblast-like synoviocytes, APCs, and macrophages are activated locally and produce various inflammatory factors. | ||
*The autoimmune response | *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. | ||
* | |||
==Genetics== | ==Genetics== | ||
Revision as of 20:50, 23 March 2018
|
Rheumatoid arthritis Microchapters | |
|
Diagnosis | |
|---|---|
|
Treatment | |
|
Case Studies | |
|
Rheumatoid arthritis pathophysiology On the Web | |
|
American Roentgen Ray Society Images of Rheumatoid arthritis pathophysiology | |
|
Risk calculators and risk factors for Rheumatoid arthritis pathophysiology | |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]
Overview
The exact pathogenesis of [disease name] is not fully understood.
OR
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
OR
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
OR
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
OR
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
OR
The progression to [disease name] usually involves the [molecular pathway].
OR
The pathophysiology of [disease/malignancy] depends on the histological subtype.
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 inflammatory and destruction of the synovial membrane.
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.
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, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
- On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
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.