clinical science session : gout - newer understanding in the pathogenesis of gout - dr vikas...
TRANSCRIPT
![Page 1: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/1.jpg)
Newer understanding in the pathogenesis of gout
Prof. Vikas AgarwalClinical Immunology,SGPGIMS, Lucknow
![Page 2: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/2.jpg)
Layout• Genetics• Environmental factors• Host factors Urate clearance Dysregulated innate immunity Role of neutrophils Resolution of acute attack
![Page 3: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/3.jpg)
Layout• Genetics• Environmental factors• Host factors Urate clearance Dysregulated innate immunity Role of neutrophils Resolution of acute attack• Therapeutic insights
![Page 4: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/4.jpg)
Uric acid metabolism
Firestein and Kelley’s Textbook of Rheumatology 10 th Edition 2017
OVERPRODUCERS•HGPRT1 deficiency•PRPP synthetase hyperactivity
![Page 5: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/5.jpg)
Uric acid transport proteins
Arthritis Research & Therapy (2015) 17:98
![Page 6: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/6.jpg)
GWAS studies
Rheum Dis Clin N Am 40 (2014) 279–290
Common in most studies•SLC2A9•ABCG2•SLC22A12
![Page 7: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/7.jpg)
Layout• Genetics• Environmental factors• Host factors Urate clearance Dysregulated innate immunity Role of neutrophils Resolution of acute attack• Therapeutic insights
![Page 8: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/8.jpg)
Dietary factors
Rheum Dis Clin North Am. 2014 November ; 40(4): 581–604.
![Page 9: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/9.jpg)
Fructose (soft drinks)
Firestein and Kelley’s Textbook of Rheumatology 10th Edition 2017
![Page 10: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/10.jpg)
Layout• Genetics• Environmental factors• Host factors Urate clearance Dysregulated innate immunity Role of neutrophils Resolution of acute attack• Therapeutic insights
![Page 11: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/11.jpg)
Gene environment interaction - SLC2A9 genotype and sugar exposure
Arthritis Research & Therapy (2015) 17:98
![Page 12: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/12.jpg)
Patients with gout handle urate load differently
Joint Bone Spine (2016) (online first)
![Page 13: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/13.jpg)
Layout• Genetics• Environmental factors• Host factors Urate clearance Dysregulated innate immunity Role of neutrophils Resolution of acute attack• Therapeutic insights
![Page 14: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/14.jpg)
Initiation of acute gout attack
Semin Immunopathol (2013) 35:501–512
![Page 15: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/15.jpg)
J Mol Med 2015; 93(7):727-34.
![Page 16: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/16.jpg)
Acute gout
RMD Open 2015;1:e000046.
![Page 17: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/17.jpg)
Layout• Genetics• Environmental factors• Host factors Urate clearance Dysregulated innate immunity Role of neutrophils Resolution of acute attack• Therapeutic insights
![Page 18: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/18.jpg)
Neutrophils• Most abundant leukocytes in blood: 50-70%• Antimicrobial defense
– Chemotaxis– Intracellular killing
• Oxidative: ROS• Non Oxidative- Proteases
•Neutrophil Extracellular Traps (NETs)
![Page 19: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/19.jpg)
![Page 20: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/20.jpg)
![Page 21: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/21.jpg)
Neutrophils and NETS
Semin Immunopathol (2013) 35:501–512
![Page 22: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/22.jpg)
Ex-vivo activation of neutrophils when exposed to gout synovial fluid
Semin Immunopathol (2013) 35:501–512
![Page 23: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/23.jpg)
J Mol Med 2015; 93(7):727-34.
![Page 24: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/24.jpg)
Summary – acute gout
RMD Open 2015;1:e000046.
![Page 25: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/25.jpg)
Layout• Genetics• Environmental factors• Host factors Urate clearance Dysregulated innate immunity Role of neutrophils Resolution of acute attack• Therapeutic insights
![Page 26: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/26.jpg)
Resolution of acute attacks• NETs• IL-37• Anti-inflammatory cytokines - IL-10, TGF-β• ACTH, MSH
![Page 27: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/27.jpg)
Aggregated NETs limit inflammation by degrading cytokines and chemokines
Nat Med. 2014 May;20(5):511-7
![Page 28: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/28.jpg)
Aggregated NETs limit inflammation by degrading cytokines and chemokines
Nature Reviews Rheumatology 10, 319 (2014)
Nat Med. 2014 May;20(5):511-7
![Page 29: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/29.jpg)
![Page 30: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/30.jpg)
Expression of IL-37 in patients with gouty arthritis
SYNOVIUM
TOPHI
![Page 31: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/31.jpg)
![Page 32: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/32.jpg)
![Page 33: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/33.jpg)
RMD Open 2015;1:e000046.
![Page 34: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/34.jpg)
![Page 35: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/35.jpg)
![Page 36: CLINICAL SCIENCE SESSION : GOUT - Newer understanding in the pathogenesis of gout - Dr Vikas Agarwal](https://reader035.vdocuments.us/reader035/viewer/2022070509/58a2982a1a28ab36508b6e45/html5/thumbnails/36.jpg)
Neutrophil extracellular traps mediate
A. Inflammation in acute attack of goutB. Helps in resolution of acute attack of goutC. BothD. None