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==Pathophysiology==
The pathophysiology of Enteropathic arthropathy:<ref name="pmid3649644">{{cite journal |vauthors=Navis ES |title=Controlling violent patients before they control you. Advice on keeping your cool when your patient is losing his |journal=Nursing |volume=17 |issue=9 |pages=52–4 |date=September 1987 |pmid=3649644 |doi= |url=}}</ref><ref name="pmid3495471">{{cite journal |vauthors=Cuvelier C, Barbatis C, Mielants H, De Vos M, Roels H, Veys E |title=Histopathology of intestinal inflammation related to reactive arthritis |journal=Gut |volume=28 |issue=4 |pages=394–401 |date=April 1987 |pmid=3495471 |pmc=1432823 |doi= |url=}}</ref><ref name="pmid20485176">{{cite journal |vauthors=Jacques P, Elewaut D, Mielants H |title=Interactions between gut inflammation and arthritis/spondylitis |journal=Curr Opin Rheumatol |volume=22 |issue=4 |pages=368–74 |date=July 2010 |pmid=20485176 |doi=10.1097/BOR.0b013e3283393807 |url=}}</ref><ref name="pmid1001980">{{cite journal |vauthors=Mallas EG, Mackintosh P, Asquith P, Cooke WT |title=Histocompatibility antigens in inflammatory bowel disease. Their clinical significance and their association with arthropathy with special reference to HLA-B27 (W27) |journal=Gut |volume=17 |issue=11 |pages=906–10 |date=November 1976 |pmid=1001980 |pmc=1411211 |doi= |url=}}</ref><ref name="pmid8733445">{{cite journal |vauthors=Brown MA, Pile KD, Kennedy LG, Calin A, Darke C, Bell J, Wordsworth BP, Cornélis F |title=HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom |journal=Ann. Rheum. Dis. |volume=55 |issue=4 |pages=268–70 |date=April 1996 |pmid=8733445 |pmc=1010149 |doi= |url=}}</ref><ref name="pmid10640771">{{cite journal |vauthors=Mertz AK, Wu P, Sturniolo T, Stoll D, Rudwaleit M, Lauster R, Braun J, Sieper J |title=Multispecific CD4+ T cell response to a single 12-mer epitope of the immunodominant heat-shock protein 60 of Yersinia enterocolitica in Yersinia-triggered reactive arthritis: overlap with the B27-restricted CD8 epitope, functional properties, and epitope presentation by multiple DR alleles |journal=J. Immunol. |volume=164 |issue=3 |pages=1529–37 |date=February 2000 |pmid=10640771 |doi= |url=}}</ref><ref name="pmid19468997">{{cite journal |vauthors=Fantini MC, Pallone F, Monteleone G |title=Common immunologic mechanisms in inflammatory bowel disease and spondylarthropathies |journal=World J. Gastroenterol. |volume=15 |issue=20 |pages=2472–8 |date=May 2009 |pmid=19468997 |pmc=2686905 |doi= |url=}}</ref><ref name="pmid7964509">{{cite journal |vauthors=Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernández-Sueiro JL, Balish E, Hammer RE |title=The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats |journal=J. Exp. Med. |volume=180 |issue=6 |pages=2359–64 |date=December 1994 |pmid=7964509 |pmc=2191772 |doi= |url=}}</ref><ref name="pmid15539413">{{cite journal |vauthors=Laukens D, Peeters H, Marichal D, Vander Cruyssen B, Mielants H, Elewaut D, Demetter P, Cuvelier C, Van Den Berghe M, Rottiers P, Veys EM, Remaut E, Steidler L, De Keyser F, De Vos M |title=CARD15 gene polymorphisms in patients with spondyloarthropathies identify a specific phenotype previously related to Crohn's disease |journal=Ann. Rheum. Dis. |volume=64 |issue=6 |pages=930–5 |date=June 2005 |pmid=15539413 |pmc=1755516 |doi=10.1136/ard.2004.028837 |url=}}</ref><ref name="pmid16937463">{{cite journal |vauthors=Rothfuss KS, Stange EF, Herrlinger KR |title=Extraintestinal manifestations and complications in inflammatory bowel diseases |journal=World J. Gastroenterol. |volume=12 |issue=30 |pages=4819–31 |date=August 2006 |pmid=16937463 |pmc=4087615 |doi= |url=}}</ref>
*The initial research of esophageal acid clearance in patients with reflux esophagitis cautioned that acid clearance time become nearly continuously longer within the patients than in regular patients.
*Although the pathogenesis of EA has not been plainly clarified, the observation that joint inflammation occurs in genetically predisposed subjects with bacterial gut infections provided an important evidence for a possible relationship between inflammation of the gut mucosa and arthritis.
*Subsequent research, but, demonstrated that enormous overlap in acid clearance times took place among patients and controls.
*Current theories provide, in genetically predisposed subjects, an aberrant migration of intestinal lymphocytes or macrophages from inflamed gut mucosa to joints, in which an important role was played by gut bacteria.
*As a consequence, some patients with reflux signs and symptoms exhibit normal esophageal acid clearance times whereas in other patients acid clearance is abnormally long.
*In fact, a dysfunctional interaction between the mucosal immune system and gut bacteria could result in an abnormal state of immunological tolerance toward flora by alterations in mucosal effector cells or by affecting regulatory cells.
*What accounts for delayed acid clearance in a number of the patients?
*A significant evidence for the pathogenic role of gut bacteria in the pathogenesis of SpA is derived from animals models.
*One apparent candidate as a purpose for delayed esophageal clearance is an atypical esophageal motor function.
*Genetic factors play a predisposing role while environmental factors, such as infectious agents, may play a causative role.
*Abnormal esophageal motility is generally associated with extended acid clearance, not all individuals with delayed acid clearance, but, have the overt peristaltic disorder.
*Among the genetic factors, HLA-B27 has the strongest genetic association with SpA and in particular with ankylosing spondylitis (AS).  
*Unfortunately, the challenge of esophageal-body motor function in patients with reflux esophagitis has received negligible attention.
*This association is reported in more than 90% of cases, also spondylitis in IBD is associated with the presence of HLA-B27, however, in lower frequencies than in AS (30%–80%).  
*Earlier reports primarily based on manometry with non-infused catheters recommended that most of the people of sufferers show up the disordered esophageal motor hobby after deglutition.
*Pure asymptomatic sacroiliitis in CD is not strongly associated with HLA-B27 and a very recent study indicates a prevalence of 7%.  
*The major motor abnormality appeared to be an increased incidence of nonperistaltic contractions, often repetitive, inside the distal esophagus.
*In 2000, Orchard et al. described an association with HLA-DR0103, B35, and B27 in type 1 peripheral arthritis and neither B27 nor DR4 associations were observed in type 2 arthritis.
these contractions were believed to cause ineffective esophageal emptying in recumbent patients.
*In order to describe the role of HLA-B27 in the pathogenesis of EA, different theories have been proposed.
*Subsequent studies the use of infused-catheter manometry suggests that many, if not the majority, of patients with reflux esophagitis, have overtly regular primary peristalsis.
*One theory suggests that HLA-B27-expressing macrophages expose specific bacterial antigens that may activate CD4+ T-cells with their migration from gut to joint with the development of arthritis.
*The latest study indicates that that patients with reflux esophagitis and controls have a similar excessive frequency of swallowing in the conscious nation and occasional frequency whilst asleep.
*Another theory proposes that homology between HLA-B27 sequences and bacterial antigens may activate T-cell and inflammation by antigen mimicry mechanism.  
*Extra statistics are wished, however, approximately swallowing frequency and occurrence of intact primary peristaltic sequences in the esophagitis patients.
*Finally, the most recent theory is based on the endoplasmic reticulum stress: under normal conditions, the peptide-loaded HLA class I heavy chain binds the β2-microglobulin (β2m) in the endoplasmic reticulum. The folding process of the HLA-B27 heavy chain is slower than that of other HLA alleles thus leading to the generation of misfolded chains.  
*Even much less is understood approximately secondary peristalsis in patients with reflux esophagitis.
*Misfolded chains are usually removed in the endoplasmic reticulum, but in certain conditions, such as viral infection, they accumulate thus activating the protein BiP, the endoplasmic reticulum-unfolded-protein-response (UPR) and the nuclear factor κB (NFκB), which play a critical role in the induction of inflammation.  
*In patients with reflux esophagitis followed via esophageal-body motor dysfunction, the motor abnormality may both antedate the reflux esophagitis or be as a result of the esophagitis. again, the choice wants no longer be "either-or." we've got located each variety of circumstances.
*Data suggest that deposition of β2m, caused by the high dissociation rate between the HLA-B27 heavy chain and β2m, occurring within synovial tissue, may lead to the initiation of chronic inflammation.
*In some patients, esophageal motor abnormalities improve or disappear after recuperation of reflux esophagitis.
*Other HLA genes have been associated with SpA in IBD: HLA-DrB10103, HLA-B35, HLA-B24 in type 1 peripheral arthritis, and HLA-B44 in type 2 peripheral arthritis.  
*This collection argues that the motor abnormality became secondary.
*Moreover, Mielants et al. showed an association between HLA-Bw62 and chronic gut lesions associated with a family history of AS and CD, with markers of inflammation, reduced axial mobility, the presence of sacroiliitis, destructive joint lesions, and a diagnosis of AS.
*In different patients, esophageal motor dysfunction persists after complete resolution of reflux esophagitis.
*Further confirming the relevance of HLA-B27 in the pathogenesis of enteroarthritis, Hammer et al. studied transgenic rats overexpressing HLA-B27 molecule. These rats developed a multisystemic inflammatory disease that had several clinical and histopathological similarities to SpA and IBD [54]. An important finding was that these rats did not develop joint or gut inflammation when they were in a germ-free environment [55]. This result supports the theory of the participation of microorganisms in the pathogenesis of these diseases.
*This finding indicates that the motor disorder either preceded reflux esophagitis or the esophagitis turned into sufficiently intense to motive permanent damage to esophageal muscle or nerves.
*In humans with reactive arthritis, following Yersinia enterocolitica, Shigella spp. or Salmonella enteritidis and Typhimurium infection, bacterial antigens have been detected in joints [56–59]. Later studies further confirmed this evidence.
*regardless of whether or not the esophageal motor disorder is number one or secondary, this option, as soon as the present, may also create a vicious cycle wherein esophageal motor disorder leads to increasingly severe reflux esophagitis that during turn similarly impairs esophageal motor function.
*Other molecular studies found similarities between Klebsiella nitrogenase and HLA-B27 and between Klebsiella pullulanase and collagen fibers types I, III, and IV.  
A 2nd factor that could cause delayed acid clearance is abnormal salivation.
*Interestingly, elevated levels of antibodies against Klebsiella and collagen fibers types I, III, IV, and V were detected in patients with CD and AS.
diminished salivation would decrease: (a) swallowing frequency and (b) the quantity of saliva available to dilute, neutralize, and washout esophageal acid.
*In addition to HLA-B27, other genes have been identified as being related to SpA and IBD. In fact, several common genetic predispositions between SpA and IBD were identified, of which the association with IL-23R polymorphisms is most prominent.  
*Some other possible abnormality of saliva is a decreased capability for acid neutralization. Even though salivation is known to be defective in certain disease entities which includes Sjogren's syndrome, salivary flow and content remain to be comprehensively analyzed in patients with reflux esophagitis.
*The functional role of IL-23 receptor polymorphisms remains unclear, the fact that IL-23 signaling plays a critical role in the Th17-mediated inflammation indicates that Th17 cells may represent a common pathogenetic mechanism in both IBD and SpA.  
*Irrespective of the underlying purpose, not on time esophageal clearance promotes esophageal exposure to the refluxed fabric.  
*The first susceptibility gene that has been identified for CD is CARD15 (or NOD2). Variants within this gene increase the risk for CD by threefold for heterozygous and fortyfold for homozygous individuals.  
*A few patients with reflux esophagitis may additionally have the same frequency of GE reflux as healthy patients, but sustain an immoderate esophageal exposure to acid because of an abnormality in esophageal acid clearance.
*An association was also found in SpA patients between the carriage of CARD15 variants and the development of chronic subclinical gut inflammation.  
 
*Although CARD15 mutations do not seem to predispose to arthritis, it might confer a risk towards the development of (sub) clinical gut inflammation in SpA patients, rendering these patients more disposed to develop IBD.
==Natural history==
*A CARD15-mediated NFκB-dependent inflammatory reaction might be an important pathogenic process within the joints.  
*Rex et al and Palmer produced follow up studies showing that 35-39% of oesophagitis patients improved with time. While some more recent studies similarly suggested that a significant proportion of oesophagitis or GORD patients do very well, others have reported the reverse.
*The protein is expressed in the joint tissue, and bacterial cell wall components have been demonstrated in the synovium of SpA patients, supporting the idea that CARD15 can locally trigger inflammation.  
*Follow up periods were very variable, however, and few of these studies concentrated
*Recently, additionally shared associations between SpA and IBD were found at chromosome 1q32 near KIF21B (genome-wide significant), STAT3, IL-12B, CDKAL1, LRRK2/MUC19, and chromosome 13q14 (experiment-wise association).  
on the clearly defined group of GORD patients with oesophagitis.  
*As the genes IL-23R, STAT3, and IL-12B all influence Th17 lymphocyte differentiation/activation, this provides further evidence implicating the Th17 lymphocyte subset in the pathogenesis of SpA.
It shows the natural history of the condition more than 10 years after diagnosis. One of the most striking findings relates to the frequency of heartburn among responders. More than half had heartburn at least weekly despite the fact that 55% of these symptomatic patients were taking daily acid suppression treatment, and in total over three quarters either had frequent symptoms or took regular antireflux medication. This suggests a worse prognosis than previous reports,23 24 27 but the discrepancies probably result from their inclusion of patients with less severe GORD or a hiatus hernia alone. The rate of stricture formation (2%) in this study is lower than that quoted by others.
*In addition to genetic susceptibility, an important role was also been given to the environmental factors in triggering the onset of disease.  
This may be explained by the fact that previous studies investigating complications have concentrated on those patients with resistant disease, whereas we followed up consecutive, non-complicated cases, most of whom had been discharged from hospital follow up years previously. This would suggest that our lower figure more accurately represents the natural history of all oesophagitis patients. However, not all patients with dysphagia weekly or more often, or daily heartburn, agreed to repeat endoscopy, so it is possible that strictures may have been missed in our study. It could also be argued that our incidence of one patient developing Barrett's mucosa is too low, again because of the low uptake of repeat endoscopy.
*In fact, bacterial gut infections such as Yersinia enterocolitica, Salmonella typhimurium, Campylobacter jejuni, and Shigella spp may cause joint inflammation in genetically predisposed patients.  
The finding that grade of oesophagitis did not influence the level of symptoms or quality of life scores at review is in keeping with the findings of others who have reported that oesophagitis grade is not a useful predictor of longterm outcome.'0 12 However, those with more severe esophagitis did have significantly higher consumption of both H2RAs and proton pump inhibitors.  
*Given the prototypical link between certain bacterial infections and the onset of reactive arthritis, several studies have aimed to assess the role of intestinal flora in disease progression, as well as the resulting changes in mucosal response.  
*Our finding that age at the time of diagnosis is the only independent predictor of outcome after diagnosis of oesophagitis has not been previously reported.  
*On the basis of these observations, the possible pathways involved in joint and gut inflammation in EA may be the following: in the acute phase of inflammation, bacterial infections can cause acute intestinal inflammation.
*Hiatus hernia and complications of oesophagitis (Barrett's mucosa and stricture) are more common over the age of 50 years,8 which may explain' why those with a worse outcome in this study were older than the comparatively asymptomatic group receiving no treatment.
*Certain bacteria may survive intracellularly in macrophages that can traffic to the joint and cause arthritis in a genetically predisposed host. *Proinflammatory cytokines such as TNF and IL-23 are produced locally, with Paneth cells being the most important producers of IL-23 in the intestine.  
*This expression can activate innate immune cells (NK) to produce IL-22 that may help control inflammation at mucosal sites.  
*Otherwise, damage and pathogen-associated molecular pattern molecules (DAMPs and PAMPs) and cellular stretch might promote initiation of joint inflammation.
*In the transition phase, acute intestinal and articular inflammation can be sustained due to defective immune regulation by TREG cells, or by ER stress, whereas iNKT cells act as regulators to control inflammation. Proangiogenic factors such as PlGF can lead to aberrant neovascularisation. *These events may lead to chronicity, further enhanced or maintained by repetitive cellular stress.
*In this stage, stromal cells become more important, as targets for proinflammatory cytokines
*
*
*
*
<references />

Latest revision as of 19:12, 11 April 2018

The pathophysiology of Enteropathic arthropathy:[1][2][3][4][5][6][7][8][9][10]

  • Although the pathogenesis of EA has not been plainly clarified, the observation that joint inflammation occurs in genetically predisposed subjects with bacterial gut infections provided an important evidence for a possible relationship between inflammation of the gut mucosa and arthritis.
  • Current theories provide, in genetically predisposed subjects, an aberrant migration of intestinal lymphocytes or macrophages from inflamed gut mucosa to joints, in which an important role was played by gut bacteria.
  • In fact, a dysfunctional interaction between the mucosal immune system and gut bacteria could result in an abnormal state of immunological tolerance toward flora by alterations in mucosal effector cells or by affecting regulatory cells.
  • A significant evidence for the pathogenic role of gut bacteria in the pathogenesis of SpA is derived from animals models.
  • Genetic factors play a predisposing role while environmental factors, such as infectious agents, may play a causative role.
  • Among the genetic factors, HLA-B27 has the strongest genetic association with SpA and in particular with ankylosing spondylitis (AS).
  • This association is reported in more than 90% of cases, also spondylitis in IBD is associated with the presence of HLA-B27, however, in lower frequencies than in AS (30%–80%).
  • Pure asymptomatic sacroiliitis in CD is not strongly associated with HLA-B27 and a very recent study indicates a prevalence of 7%.
  • In 2000, Orchard et al. described an association with HLA-DR0103, B35, and B27 in type 1 peripheral arthritis and neither B27 nor DR4 associations were observed in type 2 arthritis.
  • In order to describe the role of HLA-B27 in the pathogenesis of EA, different theories have been proposed.
  • One theory suggests that HLA-B27-expressing macrophages expose specific bacterial antigens that may activate CD4+ T-cells with their migration from gut to joint with the development of arthritis.
  • Another theory proposes that homology between HLA-B27 sequences and bacterial antigens may activate T-cell and inflammation by antigen mimicry mechanism.
  • Finally, the most recent theory is based on the endoplasmic reticulum stress: under normal conditions, the peptide-loaded HLA class I heavy chain binds the β2-microglobulin (β2m) in the endoplasmic reticulum. The folding process of the HLA-B27 heavy chain is slower than that of other HLA alleles thus leading to the generation of misfolded chains.
  • Misfolded chains are usually removed in the endoplasmic reticulum, but in certain conditions, such as viral infection, they accumulate thus activating the protein BiP, the endoplasmic reticulum-unfolded-protein-response (UPR) and the nuclear factor κB (NFκB), which play a critical role in the induction of inflammation.
  • Data suggest that deposition of β2m, caused by the high dissociation rate between the HLA-B27 heavy chain and β2m, occurring within synovial tissue, may lead to the initiation of chronic inflammation.
  • Other HLA genes have been associated with SpA in IBD: HLA-DrB10103, HLA-B35, HLA-B24 in type 1 peripheral arthritis, and HLA-B44 in type 2 peripheral arthritis.
  • Moreover, Mielants et al. showed an association between HLA-Bw62 and chronic gut lesions associated with a family history of AS and CD, with markers of inflammation, reduced axial mobility, the presence of sacroiliitis, destructive joint lesions, and a diagnosis of AS.
  • Further confirming the relevance of HLA-B27 in the pathogenesis of enteroarthritis, Hammer et al. studied transgenic rats overexpressing HLA-B27 molecule. These rats developed a multisystemic inflammatory disease that had several clinical and histopathological similarities to SpA and IBD [54]. An important finding was that these rats did not develop joint or gut inflammation when they were in a germ-free environment [55]. This result supports the theory of the participation of microorganisms in the pathogenesis of these diseases.
  • In humans with reactive arthritis, following Yersinia enterocolitica, Shigella spp. or Salmonella enteritidis and Typhimurium infection, bacterial antigens have been detected in joints [56–59]. Later studies further confirmed this evidence.
  • Other molecular studies found similarities between Klebsiella nitrogenase and HLA-B27 and between Klebsiella pullulanase and collagen fibers types I, III, and IV.
  • Interestingly, elevated levels of antibodies against Klebsiella and collagen fibers types I, III, IV, and V were detected in patients with CD and AS.
  • In addition to HLA-B27, other genes have been identified as being related to SpA and IBD. In fact, several common genetic predispositions between SpA and IBD were identified, of which the association with IL-23R polymorphisms is most prominent.
  • The functional role of IL-23 receptor polymorphisms remains unclear, the fact that IL-23 signaling plays a critical role in the Th17-mediated inflammation indicates that Th17 cells may represent a common pathogenetic mechanism in both IBD and SpA.
  • The first susceptibility gene that has been identified for CD is CARD15 (or NOD2). Variants within this gene increase the risk for CD by threefold for heterozygous and fortyfold for homozygous individuals.
  • An association was also found in SpA patients between the carriage of CARD15 variants and the development of chronic subclinical gut inflammation.
  • Although CARD15 mutations do not seem to predispose to arthritis, it might confer a risk towards the development of (sub) clinical gut inflammation in SpA patients, rendering these patients more disposed to develop IBD.
  • A CARD15-mediated NFκB-dependent inflammatory reaction might be an important pathogenic process within the joints.
  • The protein is expressed in the joint tissue, and bacterial cell wall components have been demonstrated in the synovium of SpA patients, supporting the idea that CARD15 can locally trigger inflammation.
  • Recently, additionally shared associations between SpA and IBD were found at chromosome 1q32 near KIF21B (genome-wide significant), STAT3, IL-12B, CDKAL1, LRRK2/MUC19, and chromosome 13q14 (experiment-wise association).
  • As the genes IL-23R, STAT3, and IL-12B all influence Th17 lymphocyte differentiation/activation, this provides further evidence implicating the Th17 lymphocyte subset in the pathogenesis of SpA.
  • In addition to genetic susceptibility, an important role was also been given to the environmental factors in triggering the onset of disease.
  • In fact, bacterial gut infections such as Yersinia enterocolitica, Salmonella typhimurium, Campylobacter jejuni, and Shigella spp may cause joint inflammation in genetically predisposed patients.
  • Given the prototypical link between certain bacterial infections and the onset of reactive arthritis, several studies have aimed to assess the role of intestinal flora in disease progression, as well as the resulting changes in mucosal response.
  • On the basis of these observations, the possible pathways involved in joint and gut inflammation in EA may be the following: in the acute phase of inflammation, bacterial infections can cause acute intestinal inflammation.
  • Certain bacteria may survive intracellularly in macrophages that can traffic to the joint and cause arthritis in a genetically predisposed host. *Proinflammatory cytokines such as TNF and IL-23 are produced locally, with Paneth cells being the most important producers of IL-23 in the intestine.
  • This expression can activate innate immune cells (NK) to produce IL-22 that may help control inflammation at mucosal sites.
  • Otherwise, damage and pathogen-associated molecular pattern molecules (DAMPs and PAMPs) and cellular stretch might promote initiation of joint inflammation.
  • In the transition phase, acute intestinal and articular inflammation can be sustained due to defective immune regulation by TREG cells, or by ER stress, whereas iNKT cells act as regulators to control inflammation. Proangiogenic factors such as PlGF can lead to aberrant neovascularisation. *These events may lead to chronicity, further enhanced or maintained by repetitive cellular stress.
  • In this stage, stromal cells become more important, as targets for proinflammatory cytokines
  1. ↑ Navis ES (September 1987). "Controlling violent patients before they control you. Advice on keeping your cool when your patient is losing his". Nursing. 17 (9): 52–4. PMID 3649644.
  2. ↑ Cuvelier C, Barbatis C, Mielants H, De Vos M, Roels H, Veys E (April 1987). "Histopathology of intestinal inflammation related to reactive arthritis". Gut. 28 (4): 394–401. PMC 1432823. PMID 3495471.
  3. ↑ Jacques P, Elewaut D, Mielants H (July 2010). "Interactions between gut inflammation and arthritis/spondylitis". Curr Opin Rheumatol. 22 (4): 368–74. doi:10.1097/BOR.0b013e3283393807. PMID 20485176.
  4. ↑ Mallas EG, Mackintosh P, Asquith P, Cooke WT (November 1976). "Histocompatibility antigens in inflammatory bowel disease. Their clinical significance and their association with arthropathy with special reference to HLA-B27 (W27)". Gut. 17 (11): 906–10. PMC 1411211. PMID 1001980.
  5. ↑ Brown MA, Pile KD, Kennedy LG, Calin A, Darke C, Bell J, Wordsworth BP, Cornélis F (April 1996). "HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom". Ann. Rheum. Dis. 55 (4): 268–70. PMC 1010149. PMID 8733445.
  6. ↑ Mertz AK, Wu P, Sturniolo T, Stoll D, Rudwaleit M, Lauster R, Braun J, Sieper J (February 2000). "Multispecific CD4+ T cell response to a single 12-mer epitope of the immunodominant heat-shock protein 60 of Yersinia enterocolitica in Yersinia-triggered reactive arthritis: overlap with the B27-restricted CD8 epitope, functional properties, and epitope presentation by multiple DR alleles". J. Immunol. 164 (3): 1529–37. PMID 10640771.
  7. ↑ Fantini MC, Pallone F, Monteleone G (May 2009). "Common immunologic mechanisms in inflammatory bowel disease and spondylarthropathies". World J. Gastroenterol. 15 (20): 2472–8. PMC 2686905. PMID 19468997.
  8. ↑ Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernández-Sueiro JL, Balish E, Hammer RE (December 1994). "The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats". J. Exp. Med. 180 (6): 2359–64. PMC 2191772. PMID 7964509.
  9. ↑ Laukens D, Peeters H, Marichal D, Vander Cruyssen B, Mielants H, Elewaut D, Demetter P, Cuvelier C, Van Den Berghe M, Rottiers P, Veys EM, Remaut E, Steidler L, De Keyser F, De Vos M (June 2005). "CARD15 gene polymorphisms in patients with spondyloarthropathies identify a specific phenotype previously related to Crohn's disease". Ann. Rheum. Dis. 64 (6): 930–5. doi:10.1136/ard.2004.028837. PMC 1755516. PMID 15539413.
  10. ↑ Rothfuss KS, Stange EF, Herrlinger KR (August 2006). "Extraintestinal manifestations and complications in inflammatory bowel diseases". World J. Gastroenterol. 12 (30): 4819–31. PMC 4087615. PMID 16937463.
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