Rheumatoid arthritis pathophysiology
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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
- The development of rheumatoid arthritis is the result of mutation of human leukocyte antigen (HLA) genes within the HLA region on chromosome 6.
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:[5][6]
- The earliest findings is the formation of the new synovial blood vessel.
- There is hypertrophy of synovial lining layer and infiltration of mononuclear cells.
- Chronic inflammation with lymphocytic infiltration.
- There is pannus formation.
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.
- ↑ Koch AE (November 2003). "Angiogenesis as a target in rheumatoid arthritis". Ann. Rheum. Dis. 62 Suppl 2: ii60–7. PMC 1766740. PMID 14532152.
- ↑ Koch AE (June 1998). "Review: angiogenesis: implications for rheumatoid arthritis". Arthritis Rheum. 41 (6): 951–62. doi:10.1002/1529-0131(199806)41:6<951::AID-ART2>3.0.CO;2-D. PMID 9627005.