Adult-onset Still's disease pathophysiology: Difference between revisions

Jump to navigation Jump to search
← Older editNewer edit →
VisualWikitext
Skazmi (talk | contribs)
CMEAdmin, CMEUser, Bureaucrats, nocaptcha, smwadministrator, Administrators, Widget editors
6,685 edits
Skazmi (talk | contribs)
CMEAdmin, CMEUser, Bureaucrats, nocaptcha, smwadministrator, Administrators, Widget editors
6,685 edits
Line 32: Line 32:
Both innate and adaptive immunity play roles in the pathological evolution of adult-onset Still's disease with the dysfunction occurring in the innate immunity predominating the picture. The following dysfunctions are involved:
Both innate and adaptive immunity play roles in the pathological evolution of adult-onset Still's disease with the dysfunction occurring in the innate immunity predominating the picture. The following dysfunctions are involved:


'''Innate immunity'''
'''Changes in the innate immunity'''
* Natural killer cells have been found to be decreased in patients with ASOD. The mechanism underlying dysfunctional NK cells are due to a defect in IL-18 receptor β phosphorylation.<ref name="de JagerVastert2009">{{cite journal|last1=de Jager|first1=Wilco|last2=Vastert|first2=Sebastiaan J.|last3=Beekman|first3=Jeffrey M.|last4=Wulffraat|first4=Nico M.|last5=Kuis|first5=Wietse|last6=Coffer|first6=Paul J.|last7=Prakken|first7=Berent J.|title=Defective phosphorylation of interleukin-18 receptor β causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis|journal=Arthritis & Rheumatism|volume=60|issue=9|year=2009|pages=2782–2793|issn=00043591|doi=10.1002/art.24750}}</ref>
* Natural killer cells have been found to be decreased in patients with ASOD. The mechanism underlying dysfunctional NK cells is a defect in IL-18 receptor β phosphorylation.<ref name="de JagerVastert2009">{{cite journal|last1=de Jager|first1=Wilco|last2=Vastert|first2=Sebastiaan J.|last3=Beekman|first3=Jeffrey M.|last4=Wulffraat|first4=Nico M.|last5=Kuis|first5=Wietse|last6=Coffer|first6=Paul J.|last7=Prakken|first7=Berent J.|title=Defective phosphorylation of interleukin-18 receptor β causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis|journal=Arthritis & Rheumatism|volume=60|issue=9|year=2009|pages=2782–2793|issn=00043591|doi=10.1002/art.24750}}</ref>
* Neutrophil and macrophage activation lie at the heart of pathogenesis of ASOD due to the effects of the proinflammatory interleukin-18 (IL-18) signalling.
* Neutrophil and macrophage activation lie at the heart of pathogenesis of ASOD due to the effects of the proinflammatory interleukin-18 (IL-18) signalling.
* CD64 a marker of neutrophil activation has been found to be upregulated in active ASOD.<ref name="pmid22420333">{{cite journal |vauthors=Komiya A, Matsui T, Nogi S, Iwata K, Futami H, Takaoka H, Arinuma Y, Hashimoto A, Shimada K, Ikenaka T, Nakayama H, Furukawa H, Tohma S |title=Neutrophil CD64 is upregulated in patients with active adult-onset Still's disease |journal=Scand. J. Rheumatol. |volume=41 |issue=2 |pages=156–8 |date=March 2012 |pmid=22420333 |doi=10.3109/03009742.2011.644325 |url=}}</ref>
* CD64, a marker of neutrophil activation has been found to be upregulated in active ASOD.<ref name="pmid22420333">{{cite journal |vauthors=Komiya A, Matsui T, Nogi S, Iwata K, Futami H, Takaoka H, Arinuma Y, Hashimoto A, Shimada K, Ikenaka T, Nakayama H, Furukawa H, Tohma S |title=Neutrophil CD64 is upregulated in patients with active adult-onset Still's disease |journal=Scand. J. Rheumatol. |volume=41 |issue=2 |pages=156–8 |date=March 2012 |pmid=22420333 |doi=10.3109/03009742.2011.644325 |url=}}</ref>
* Macrophage colony stimulating factor, intercellular adhesion molecule-1 (ICAM-1) and calprotectin are elevated and act as markers of active disease.<ref name="pmid15934126">{{cite journal |vauthors=Chen DY, Lan JL, Lin FJ, Hsieh TY |title=Association of intercellular adhesion molecule-1 with clinical manifestations and interleukin-18 in patients with active, untreated adult-onset Still's disease |journal=Arthritis Rheum. |volume=53 |issue=3 |pages=320–7 |date=June 2005 |pmid=15934126 |doi=10.1002/art.21164 |url=}}</ref><ref name="pmid10371293">{{cite journal |vauthors=Matsui K, Tsuchida T, Hiroishi K, Tominaga K, Hayashi N, Hada T, Higashino K |title=High serum level of macrophage-colony stimulating factor (M-CSF) in adult-onset Still's disease |journal=Rheumatology (Oxford) |volume=38 |issue=5 |pages=477–8 |date=May 1999 |pmid=10371293 |doi= |url=}}</ref>
* Macrophage colony stimulating factor (MCSF), intercellular adhesion molecule-1 (ICAM-1) and calprotectin are elevated and act as markers of active disease.<ref name="pmid15934126">{{cite journal |vauthors=Chen DY, Lan JL, Lin FJ, Hsieh TY |title=Association of intercellular adhesion molecule-1 with clinical manifestations and interleukin-18 in patients with active, untreated adult-onset Still's disease |journal=Arthritis Rheum. |volume=53 |issue=3 |pages=320–7 |date=June 2005 |pmid=15934126 |doi=10.1002/art.21164 |url=}}</ref><ref name="pmid10371293">{{cite journal |vauthors=Matsui K, Tsuchida T, Hiroishi K, Tominaga K, Hayashi N, Hada T, Higashino K |title=High serum level of macrophage-colony stimulating factor (M-CSF) in adult-onset Still's disease |journal=Rheumatology (Oxford) |volume=38 |issue=5 |pages=477–8 |date=May 1999 |pmid=10371293 |doi= |url=}}</ref>
'''Adaptive immunity'''
'''Changes in the adaptive immunity'''
* T cell activation has also been shown to play role in the pathogenesis of ASOD with Th1 subset prevailing over Th2 CD4+ T cells.
* T cell activation has also been shown to play role in the pathogenesis of ASOD with Th1 (cytotoxic) subset prevailing over Th2 CD4+ T cells.
* Increased number of Th17 cells  derived from the differentiation of naieve CD4+ T cells due to to activation by interleukin-1 beta, transforming growth factor-beta and interleukin-6.<ref name="pmid20837500">{{cite journal |vauthors=Chen DY, Chen YM, Lan JL, Lin CC, Chen HH, Hsieh CW |title=Potential role of Th17 cells in the pathogenesis of adult-onset Still's disease |journal=Rheumatology (Oxford) |volume=49 |issue=12 |pages=2305–12 |date=December 2010 |pmid=20837500 |doi=10.1093/rheumatology/keq284 |url=}}</ref><ref name="pmid16200068">{{cite journal |vauthors=Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C |title=A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 |journal=Nat. Immunol. |volume=6 |issue=11 |pages=1133–41 |date=November 2005 |pmid=16200068 |pmc=1618871 |doi=10.1038/ni1261 |url=}}</ref>
* Increased number of Th17 cells  derived from the differentiation of naieve CD4+ T cells due to to activation by interleukin-1 beta, transforming growth factor-beta and interleukin- 6 is also seen in active ASOD. <ref name="pmid20837500">{{cite journal |vauthors=Chen DY, Chen YM, Lan JL, Lin CC, Chen HH, Hsieh CW |title=Potential role of Th17 cells in the pathogenesis of adult-onset Still's disease |journal=Rheumatology (Oxford) |volume=49 |issue=12 |pages=2305–12 |date=December 2010 |pmid=20837500 |doi=10.1093/rheumatology/keq284 |url=}}</ref><ref name="pmid16200068">{{cite journal |vauthors=Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C |title=A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 |journal=Nat. Immunol. |volume=6 |issue=11 |pages=1133–41 |date=November 2005 |pmid=16200068 |pmc=1618871 |doi=10.1038/ni1261 |url=}}</ref>


=== Role of interleukin-1 beta ===
=== Role of interleukin-1 beta ===
Interleukin-i beta plays a key role in producing major characteristic features of adult-onset Still's disease. PAMPs and DAMPs lead to stimulation of protein complex nucleotide-binding oligomerization-domain-(NOD-) like receptor family, pyrin domain containing 3 (NLRP3) inflammasome (expressed in myeloid cells) and increased production of interleukin-1 beta.<ref name="pmid15851489">{{cite journal |vauthors=Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J |title=Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade |journal=J. Exp. Med. |volume=201 |issue=9 |pages=1479–86 |date=May 2005 |pmid=15851489 |pmc=2213182 |doi=10.1084/jem.20050473 |url=}}</ref>The following processes are affected by an increased production of this key interleukin:
Interleukin-i beta plays a key role in producing major characteristic features of adult-onset Still's disease. PAMPs and DAMPs lead to stimulation of protein complex nucleotide-binding oligomerization-domain-(NOD-) like receptor family, pyrin domain containing 3 (NLRP3) inflammasome (expressed in myeloid cells). The consequence of all these trigger-stimulated NOD and NLRP increasing interactions is an increased production of interleukin-1 beta.<ref name="pmid15851489">{{cite journal |vauthors=Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J |title=Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade |journal=J. Exp. Med. |volume=201 |issue=9 |pages=1479–86 |date=May 2005 |pmid=15851489 |pmc=2213182 |doi=10.1084/jem.20050473 |url=}}</ref>The following processes are affected by an increased production of this key interleukin of ASOD:


 '''Hypothalamic-pituitary axis influence'''
 '''Hypothalamic-pituitary axis influence'''


 '''Liver synthesis and secretion of acute phase proteins''' 
Activation of the hypothalmic-pitutary axis by interleukin-1 beta lead to the following changes:
 
'''''Hormonal'''''
* An increased secretion of adenocorticotrophic hormone (ACTH) and anti-diuretic hormone (ADH).
* A decreased secretion of growth hormone (GH) and somatostatin.<ref name="pmid5915585">{{cite journal |vauthors=Ward DJ, Hartog M, Ansell BM |title=Corticosteroid-induced dwarfism in Still's disease treated with human growth hormone. Clinical and metabolic effects including hydroxyproline excretion in two cases |journal=Ann. Rheum. Dis. |volume=25 |issue=5 |pages=416–21 |date=September 1966 |pmid=5915585 |pmc=2453455 |doi= |url=}}</ref>
'''''Systemic'''''
* Disturbance of the thalmic temperature regulating centres leading to fever.<ref name="urlonlinelibrary.wiley.com">{{cite web |url=https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780090112 |title=onlinelibrary.wiley.com |format= |work= |accessdate=}}</ref>
* Fatigue<ref name="pmid22611516">{{cite journal |vauthors=Rossi-Semerano L, Koné-Paut I |title=Is Still's Disease an Autoinflammatory Syndrome? |journal=Int J Inflam |volume=2012 |issue= |pages=480373 |date=2012 |pmid=22611516 |pmc=3350968 |doi=10.1155/2012/480373 |url=}}</ref>
* Anorexia<ref name="pmid226115162">{{cite journal |vauthors=Rossi-Semerano L, Koné-Paut I |title=Is Still's Disease an Autoinflammatory Syndrome? |journal=Int J Inflam |volume=2012 |issue= |pages=480373 |date=2012 |pmid=22611516 |pmc=3350968 |doi=10.1155/2012/480373 |url=}}</ref> 
'''Liver synthesis and secretion of acute phase proteins''' 


'''Osteoclasts activation and matrix metalloproteinases (MMPs) synthesis'''
'''Osteoclasts activation and matrix metalloproteinases (MMPs) synthesis'''

Revision as of 04:14, 8 April 2018


Template:Adult-onset Still's disease Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

Pathophysiology

Adult-onset Still's disease is an automminue inflammatory arthritis that typically affects adolescents and adults ranging from age 16-40 years. Major etiological mechanisms behind cause a dysfunction of the innate and cellular immunity (limited) leading to activation of effector cells of the disease.

Putative triggers

Although the pathogenesis of adult-onset Still's disease is largerly idiopathic. Triggers of ASOD lead to activation of toll-like receptors (TLR) and activation of immune system. The following triggers may be implicated as factors responsible for generating key pathological processes occurring in adult-onset Still's disease (ASOD):[1][2][3][4][5][6][7][8]

Pathogen-associated molecular patterns (PAMPs)

  • Bacteria
    • Yersinia enterocolitica
    • Chlamydophila pneumoniae
    • Brucella abortus
    • Borrelia burgdorferi
  • Viruses
    • Rubella
    • Echovirus 7
    • Mumps
    • Cytomegalovirus (CMV)
  • Fungi

Danger-associated molecular patterns (DAMPs)

  • Chemicals
  • Toxins
  • Stress

Immune dysfunction

Both innate and adaptive immunity play roles in the pathological evolution of adult-onset Still's disease with the dysfunction occurring in the innate immunity predominating the picture. The following dysfunctions are involved:

Changes in the innate immunity

  • Natural killer cells have been found to be decreased in patients with ASOD. The mechanism underlying dysfunctional NK cells is a defect in IL-18 receptor β phosphorylation.[9]
  • Neutrophil and macrophage activation lie at the heart of pathogenesis of ASOD due to the effects of the proinflammatory interleukin-18 (IL-18) signalling.
  • CD64, a marker of neutrophil activation has been found to be upregulated in active ASOD.[10]
  • Macrophage colony stimulating factor (MCSF), intercellular adhesion molecule-1 (ICAM-1) and calprotectin are elevated and act as markers of active disease.[11][12]

Changes in the adaptive immunity

  • T cell activation has also been shown to play role in the pathogenesis of ASOD with Th1 (cytotoxic) subset prevailing over Th2 CD4+ T cells.
  • Increased number of Th17 cells derived from the differentiation of naieve CD4+ T cells due to to activation by interleukin-1 beta, transforming growth factor-beta and interleukin- 6 is also seen in active ASOD. [13][14]

Role of interleukin-1 beta

Interleukin-i beta plays a key role in producing major characteristic features of adult-onset Still's disease. PAMPs and DAMPs lead to stimulation of protein complex nucleotide-binding oligomerization-domain-(NOD-) like receptor family, pyrin domain containing 3 (NLRP3) inflammasome (expressed in myeloid cells). The consequence of all these trigger-stimulated NOD and NLRP increasing interactions is an increased production of interleukin-1 beta.[15]The following processes are affected by an increased production of this key interleukin of ASOD:

 Hypothalamic-pituitary axis influence

Activation of the hypothalmic-pitutary axis by interleukin-1 beta lead to the following changes:

Hormonal

  • An increased secretion of adenocorticotrophic hormone (ACTH) and anti-diuretic hormone (ADH).
  • A decreased secretion of growth hormone (GH) and somatostatin.[16]

Systemic

  • Disturbance of the thalmic temperature regulating centres leading to fever.[17]
  • Fatigue[18]
  • Anorexia[19] 

Liver synthesis and secretion of acute phase proteins 

Osteoclasts activation and matrix metalloproteinases (MMPs) synthesis

Innate immune system cells activation

Increased gene transcription of proinflammatory molecules 

Role of interleukin-18

Role of interleukin-6

Role of interleukin-17

Role of interferon gamma

Role of tumor necrosis factor-alpha (TNF-alpha)

 Reactive hemophagocytic lymphohistiocytosis 

Genetics

Associated Conditions

Gross Pathology

Microscopic Pathology

References

  1. ↑ Perez C, Artola V (March 2001). "Adult Still's disease associated with Mycoplasma pneumoniae infection". Clin. Infect. Dis. 32 (6): E105–6. doi:10.1086/319342. PMID 11247732.
  2. ↑ Dua J, Nandagudi A, Sutcliffe N (December 2012). "Mycoplasma pneumoniae infection associated with urticarial vasculitis mimicking adult-onset Still's disease". Rheumatol. Int. 32 (12): 4053–6. doi:10.1007/s00296-011-2107-4. PMID 21918897.
  3. ↑ Escudero FJ, Len O, Falcó V, de Sevilla TF, Sellas A (June 2000). "Rubella infection in adult onset Still's disease". Ann. Rheum. Dis. 59 (6): 493. PMC 1753159. PMID 10885978.
  4. ↑ Efthimiou P, Georgy S (December 2006). "Pathogenesis and management of adult-onset Still's disease". Semin. Arthritis Rheum. 36 (3): 144–52. doi:10.1016/j.semarthrit.2006.07.001. PMID 16949136.
  5. ↑ Wouters JM, van der Veen J, van de Putte LB, de Rooij DJ (September 1988). "Adult onset Still's disease and viral infections". Ann. Rheum. Dis. 47 (9): 764–7. PMC 1003594. PMID 3178317.
  6. ↑ Ogra PL, Chiba Y, Ogra SS, Dzierba JL, Herd JK (May 1975). "Rubella-virus infection in juvenile rheumatoid arthritis". Lancet. 1 (7917): 1157–61. PMID 48775.
  7. ↑ Linnemann CC, Levinson JE, Buncher CR, Schiff GM (August 1975). "Rubella antibody levels in juvenile rheumatoid arthritis". Ann. Rheum. Dis. 34 (4): 354–8. PMC 1006427. PMID 1081377.
  8. ↑ Blotzer JW, Myers AR (1978). "Echovirus-associated polyarthritis. Report of a case with synovial fluid and synovial histologic characterization". Arthritis Rheum. 21 (8): 978–81. PMID 737022.
  9. ↑ de Jager, Wilco; Vastert, Sebastiaan J.; Beekman, Jeffrey M.; Wulffraat, Nico M.; Kuis, Wietse; Coffer, Paul J.; Prakken, Berent J. (2009). "Defective phosphorylation of interleukin-18 receptor β causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis". Arthritis & Rheumatism. 60 (9): 2782–2793. doi:10.1002/art.24750. ISSN 0004-3591.
  10. ↑ Komiya A, Matsui T, Nogi S, Iwata K, Futami H, Takaoka H, Arinuma Y, Hashimoto A, Shimada K, Ikenaka T, Nakayama H, Furukawa H, Tohma S (March 2012). "Neutrophil CD64 is upregulated in patients with active adult-onset Still's disease". Scand. J. Rheumatol. 41 (2): 156–8. doi:10.3109/03009742.2011.644325. PMID 22420333.
  11. ↑ Chen DY, Lan JL, Lin FJ, Hsieh TY (June 2005). "Association of intercellular adhesion molecule-1 with clinical manifestations and interleukin-18 in patients with active, untreated adult-onset Still's disease". Arthritis Rheum. 53 (3): 320–7. doi:10.1002/art.21164. PMID 15934126.
  12. ↑ Matsui K, Tsuchida T, Hiroishi K, Tominaga K, Hayashi N, Hada T, Higashino K (May 1999). "High serum level of macrophage-colony stimulating factor (M-CSF) in adult-onset Still's disease". Rheumatology (Oxford). 38 (5): 477–8. PMID 10371293.
  13. ↑ Chen DY, Chen YM, Lan JL, Lin CC, Chen HH, Hsieh CW (December 2010). "Potential role of Th17 cells in the pathogenesis of adult-onset Still's disease". Rheumatology (Oxford). 49 (12): 2305–12. doi:10.1093/rheumatology/keq284. PMID 20837500.
  14. ↑ Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C (November 2005). "A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17". Nat. Immunol. 6 (11): 1133–41. doi:10.1038/ni1261. PMC 1618871. PMID 16200068.
  15. ↑ Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J (May 2005). "Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade". J. Exp. Med. 201 (9): 1479–86. doi:10.1084/jem.20050473. PMC 2213182. PMID 15851489.
  16. ↑ Ward DJ, Hartog M, Ansell BM (September 1966). "Corticosteroid-induced dwarfism in Still's disease treated with human growth hormone. Clinical and metabolic effects including hydroxyproline excretion in two cases". Ann. Rheum. Dis. 25 (5): 416–21. PMC 2453455. PMID 5915585.
  17. ↑ "onlinelibrary.wiley.com".
  18. ↑ Rossi-Semerano L, Koné-Paut I (2012). "Is Still's Disease an Autoinflammatory Syndrome?". Int J Inflam. 2012: 480373. doi:10.1155/2012/480373. PMC 3350968. PMID 22611516.
  19. ↑ Rossi-Semerano L, Koné-Paut I (2012). "Is Still's Disease an Autoinflammatory Syndrome?". Int J Inflam. 2012: 480373. doi:10.1155/2012/480373. PMC 3350968. PMID 22611516.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Adult-onset_Still%27s_disease_pathophysiology&oldid=1460204"