Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype.

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Term Occurence Count Dictionary
arthritis 34 rheumatologydiseases
autoimmune disease 2 rheumatologydiseases
methotrexate 1 rheumatologydiseasesdrugs
psoriatic arthritis 19 rheumatologydiseases
sacroiliitis 20 rheumatologydiseases
synovitis 6 rheumatologydiseases
ankylosing spondylitis 4 rheumatologydiseases
ankylosis 1 rheumatologydiseases
tenosynovitis 2 rheumatologydiseases
spondylitis 5 rheumatologydiseases
cyclosporine 2 rheumatologydiseasesdrugs
rheumatoid arthritis 1 rheumatologydiseases

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cyclosporine 6432 [[9]]. Finally, there is the response to therapeutic agents directed at activated T cells (for example, cyclosporine , DAB389IL-2 or alefacept), as well as to effector pathways resulting from T-cell activation.Given the
cyclosporine 39845 example, respond with different magnitude or even direction to a given therapeutic agent (for example, cyclosporine , ustekinumab, IL-17 inhibition). Using the primary outcome measure of the American College of Rheumatology
methotrexate 5883 patients are clonally expanded with a reduction in nonspecific T-cell infiltration observed following methotrexate therapy [[7],[8]]. Fourthly, the interesting observation in the setting of advanced HIV disease that
Select Disease Character Offset Disease Term Instance
ankylosing spondylitis 22912 individual clinical characteristics using the asymmetric two-tailed Pearson chi-square method [[2]].While ankylosing spondylitis is characterised by symmetrical sacroiliitis, in PsA sacroiliitis is more likely to be asymmetric [[33]].
ankylosing spondylitis 23411 sacroiliitis and B*27:05 was male preponderant (odds ratio = 11.91), resembling the findings in ankylosing spondylitis and supporting current endeavours to group the axial spondyloarthritis together. Both B*27 haplotypes
ankylosing spondylitis 34396 some inflammatory pathways will be more analogous to those in PsO, while others may resemble those of ankylosing spondylitis .It is interesting to note that the newer genetic findings are consistent with and appear to provide
ankylosing spondylitis 38405 of patients with more severe axial bone marrow oedema on MRI that is probably related to the classic ankylosing spondylitis phenotype, while HLA-B27-negative PsA was likely to be reported as a negative MRI examination result.Figure
ankylosis 3199 varied radiographic features were present, including features such as new bone formation, osteolysis and ankylosis (Table 1). The basis for this heterogeneity had not been adequately explained. In this review, the
arthritis 73 Title: Arthritis Research & TherapyConcepts of pathogenesis in psoriatic arthritis : genotype determines clinical phenotypeOliver FitzGeraldMuhammad HaroonJon T GilesRobert WinchesterPublication
arthritis 346 5/2015Publication date (ppub): /2015AbstractThis review focuses on the genetic features of psoriatic arthritis (PsA) and their relationship to phenotypic heterogeneity in the disease, and addresses three questions:
arthritis 2266 process or one that is based on entheseal responses.Introduction and concepts of pathogenesisPsoriatic arthritis (PsA) is a heterogeneous disease with diverse clinical and radiographic manifestations. However, the
arthritis 3607 of genotype to phenotype [[2]].Table 1Phenotypic heterogeneity in a cohort of 282 cases of psoriatic arthritis Age55 ± 12Male gender134 (47)Family history of psoriasis (n = 280)175 (63)Family history of
arthritis 4082 (16)Psoriasis and PsA at same time52 (18)Nail disease244 (79) Pitting96 (34) Onycholysis155 (55)Peripheral arthritis 280 (99) Polyarthritis258 (91) Oligoarthritis21 (8)Deformed joint count, if deformity6 (4 to 12)Enthesitisa97
arthritis 4106 time52 (18)Nail disease244 (79) Pitting96 (34) Onycholysis155 (55)Peripheral arthritis280 (99) Poly arthritis 258 (91) Oligoarthritis21 (8)Deformed joint count, if deformity6 (4 to 12)Enthesitisa97 (34)Dactylitisa150
arthritis 4131 (79) Pitting96 (34) Onycholysis155 (55)Peripheral arthritis280 (99) Polyarthritis258 (91) Oligo arthritis 21 (8)Deformed joint count, if deformity6 (4 to 12)Enthesitisa97 (34)Dactylitisa150 (53)Sacroiliitisa71
arthritis 4845 (%). DMARD, disease-modifying antirheumatic drug; PASI, Psoriasis Area Severity Index; PsA, psoriatic arthritis ; TNFi, tumour necrosis factor inhibitor. aVariables used to construct the propensity score.These hypotheses
arthritis 5260 exclusive, these hypotheses present very different ideas about the initiation/causation of PsA.Psoriatic arthritis is an autoimmune diseaseSeveral features in PsA suggest that an autoimmune process may drive the disease.
arthritis 5690 shown to predominate in PsA synovial fluid with a reversal of the CD4:CD8 ratio found in rheumatoid arthritis (RA) [[6]]. Thirdly, CD8+ T cells in synovial tissue and fluid obtained from PsA patients are clonally
arthritis 8690 synovial fluid, suggesting this population of T cells may be worthy of further study [[12]].Psoriatic arthritis is an entheseal-based diseaseEver since the hypothesis published in 1998 [[13]] and through some elegant
arthritis 8945 studies [[14]], there has been growing support for the concept that the origin of inflammation in spondylo arthritis including PsA is at the enthesis. Enthesitis may be a prominent clinical feature at presentation in
arthritis 9990 sites of entheseal inflammation add further weight to these concepts.Review: genetics of psoriatic arthritis One of the striking features of PsA is that as many as 50% of PsA patients have a family history that
arthritis 10179 a family history that includes one or sometimes multiple cases of PsA, PsO, or seronegative spondylo arthritis in their blood relatives, a likelihood 40-fold greater than that of their unaffected spouses [[19]-[21]].
arthritis 12735 alleles and haplotypes associated with PsO and PsA are summarised in Box 1.New data concerning psoriatic arthritis geneticsBecause of the importance of more precisely determining the role played by HLA alleles in PsA,
arthritis 13473 from individuals presenting to a dermatologic clinic who were determined to be without features of arthritis , spondylitis or enthesitis through examination by a rheumatologist. This cohort was compared with a
arthritis 14667 PsA, PsO and healthy controls.Table 2Distribution of theHLA-C*06:02andHLA-B*57:01alleles in psoriatic arthritis does not parallel that found in cutaneous psoriasisHLA allelePsA (%),n = 359PsA versus controlPsO
arthritis 15111 as percentage or odds ratio (95% confidence interval). HLA, human leukocyte antigen; PsA, psoriatic arthritis ; PsO, cutaneous psoriasis.Figure 1Distribution of HLA-C*06:02:01 among psoriatic arthritis, psoriasis
arthritis 15202 psoriatic arthritis; PsO, cutaneous psoriasis.Figure 1Distribution of HLA-C*06:02:01 among psoriatic arthritis , psoriasis and healthy controls. Venn diagrams in each population illustrate the approximate proportion
arthritis 15398 approximate proportion of individuals that bear the allele HLA-C*06:02:01. Ctrl, control; PsA, psoriatic arthritis ; PsO, cutaneous psoriasis.Since the frequency of HLA-C*06:02 was appreciably decreased in the PsA cohort
arthritis 15809 HLA-B*39:01:01 were susceptibility alleles for PsA, but are not high-risk alleles for PsO in the absence of arthritis , and HLA-B*08:01 was associated with PsA susceptibility but appears protective for PsO, being significantly
arthritis 16541 [[3],[4]].Table 3Additional HLA-B alleles that are significantly increased or decreased in the psoriatic arthritis cohortHLA allelePsA (%),n = 359PsA versus controlPsO (%),n = 214PsO versus controlControl
arthritis 17057 as percentage or odds ratio (95% confidence interval). HLA, human leukocyte antigen; PsA, psoriatic arthritis ; PsO, cutaneous psoriasis.The number of different HLA alleles associated with PsA susceptibility, and
arthritis 19227 relatively precise molecular basis for susceptibility.Figure 2Certain HLA-B alleles in the psoriatic arthritis cohort are significantly increased in frequency compared with their frequency in cutaneous psoriasis
arthritis 19499 illustrate the approximate proportion of individuals that bear the alleles. Ctrl, control; PsA, psoriatic arthritis ; PsO, psoriasis where there is no arthritis.Table 4Amino acids in polymorphic sites of HLA-B molecules
arthritis 19543 individuals that bear the alleles. Ctrl, control; PsA, psoriatic arthritis; PsO, psoriasis where there is no arthritis .Table 4Amino acids in polymorphic sites of HLA-B molecules associated with increased or decreased psoriatic
arthritis 19661 4Amino acids in polymorphic sites of HLA-B molecules associated with increased or decreased psoriatic arthritis susceptibility and their contrasting effect on binding peptide P2 side chain anchor amino acidsHLA-B
arthritis 21289 type. The standard teaching is that PsA follows the onset of PsO by 10 to 15 years. We observed that arthritis develops much closer to the appearance of PsO in the HLA-B*27:05:02 or B*39:01:01 subset than in the
arthritis 23495 the findings in ankylosing spondylitis and supporting current endeavours to group the axial spondylo arthritis together. Both B*27 haplotypes (B*27:05-C*01:02 and B*27:05:02-C*02:02:01) were equivalently associated
arthritis 29969 0.9)0.03CI, confidence interval; HLA, human leukocyte antigen.Propensity to develop severe psoriatic arthritis As an alternative approach to studying genotype–phenotype associations, we constructed a continuous
arthritis 38278 bone oedema (20%). In addition and of interest [[40]], HLA-B27 positivity in PsA and in axial spondylo arthritis defined a group of patients with more severe axial bone marrow oedema on MRI that is probably related
arthritis 38621 result.Figure 3Contribution of positive and negative risk alleles on both chromosomes to psoriatic arthritis severity. An additive model including all genotypes positively or negatively associated with the propensity
arthritis 38767 including all genotypes positively or negatively associated with the propensity to develop severe psoriatic arthritis resulting in a composite human leukocyte antigen (HLA) risk score.For the two-thirds of PsA patients
arthritis 41361 groupings.Box 1. The most common human leukocyte antigen alleles and haplotypes implicated in psoriatic arthritis susceptibility and their location within the major histocompatibility complexAllelesAncestral extended
autoimmune disease 5276 hypotheses present very different ideas about the initiation/causation of PsA.Psoriatic arthritis is an autoimmune disease Several features in PsA suggest that an autoimmune process may drive the disease. Firstly, susceptibility
autoimmune disease 6985 state perpetuated by the continual supply of self-peptides. This is the classic explanation for an autoimmune disease as a consequence of driver clones, and one would expect to recognise one or a few immunodominant T-cell
psoriatic arthritis 63 Title: Arthritis Research & TherapyConcepts of pathogenesis in psoriatic arthritis : genotype determines clinical phenotypeOliver FitzGeraldMuhammad HaroonJon T GilesRobert WinchesterPublication
psoriatic arthritis 336 (pmc-release): 5/2015Publication date (ppub): /2015AbstractThis review focuses on the genetic features of psoriatic arthritis (PsA) and their relationship to phenotypic heterogeneity in the disease, and addresses three questions:
psoriatic arthritis 3597 relationship of genotype to phenotype [[2]].Table 1Phenotypic heterogeneity in a cohort of 282 cases of psoriatic arthritis Age55 ± 12Male gender134 (47)Family history of psoriasis (n = 280)175 (63)Family history of
psoriatic arthritis 4835 deviation or n (%). DMARD, disease-modifying antirheumatic drug; PASI, Psoriasis Area Severity Index; PsA, psoriatic arthritis ; TNFi, tumour necrosis factor inhibitor. aVariables used to construct the propensity score.These hypotheses
psoriatic arthritis 9980 [[18]] at sites of entheseal inflammation add further weight to these concepts.Review: genetics of psoriatic arthritis One of the striking features of PsA is that as many as 50% of PsA patients have a family history that
psoriatic arthritis 12725 main alleles and haplotypes associated with PsO and PsA are summarised in Box 1.New data concerning psoriatic arthritis geneticsBecause of the importance of more precisely determining the role played by HLA alleles in PsA,
psoriatic arthritis 14657 cohorts of PsA, PsO and healthy controls.Table 2Distribution of theHLA-C*06:02andHLA-B*57:01alleles in psoriatic arthritis does not parallel that found in cutaneous psoriasisHLA allelePsA (%),n = 359PsA versus controlPsO
psoriatic arthritis 15101 presented as percentage or odds ratio (95% confidence interval). HLA, human leukocyte antigen; PsA, psoriatic arthritis ; PsO, cutaneous psoriasis.Figure 1Distribution of HLA-C*06:02:01 among psoriatic arthritis, psoriasis
psoriatic arthritis 15192 antigen; PsA, psoriatic arthritis; PsO, cutaneous psoriasis.Figure 1Distribution of HLA-C*06:02:01 among psoriatic arthritis , psoriasis and healthy controls. Venn diagrams in each population illustrate the approximate proportion
psoriatic arthritis 15388 the approximate proportion of individuals that bear the allele HLA-C*06:02:01. Ctrl, control; PsA, psoriatic arthritis ; PsO, cutaneous psoriasis.Since the frequency of HLA-C*06:02 was appreciably decreased in the PsA cohort
psoriatic arthritis 16531 results [[3],[4]].Table 3Additional HLA-B alleles that are significantly increased or decreased in the psoriatic arthritis cohortHLA allelePsA (%),n = 359PsA versus controlPsO (%),n = 214PsO versus controlControl
psoriatic arthritis 17047 presented as percentage or odds ratio (95% confidence interval). HLA, human leukocyte antigen; PsA, psoriatic arthritis ; PsO, cutaneous psoriasis.The number of different HLA alleles associated with PsA susceptibility, and
psoriatic arthritis 19217 indicating a relatively precise molecular basis for susceptibility.Figure 2Certain HLA-B alleles in the psoriatic arthritis cohort are significantly increased in frequency compared with their frequency in cutaneous psoriasis
psoriatic arthritis 19489 population illustrate the approximate proportion of individuals that bear the alleles. Ctrl, control; PsA, psoriatic arthritis ; PsO, psoriasis where there is no arthritis.Table 4Amino acids in polymorphic sites of HLA-B molecules
psoriatic arthritis 19651 arthritis.Table 4Amino acids in polymorphic sites of HLA-B molecules associated with increased or decreased psoriatic arthritis susceptibility and their contrasting effect on binding peptide P2 side chain anchor amino acidsHLA-B
psoriatic arthritis 29959 (0.1 to 0.9)0.03CI, confidence interval; HLA, human leukocyte antigen.Propensity to develop severe psoriatic arthritis As an alternative approach to studying genotype–phenotype associations, we constructed a continuous
psoriatic arthritis 38611 examination result.Figure 3Contribution of positive and negative risk alleles on both chromosomes to psoriatic arthritis severity. An additive model including all genotypes positively or negatively associated with the propensity
psoriatic arthritis 38757 model including all genotypes positively or negatively associated with the propensity to develop severe psoriatic arthritis resulting in a composite human leukocyte antigen (HLA) risk score.For the two-thirds of PsA patients
psoriatic arthritis 41351 genotypic groupings.Box 1. The most common human leukocyte antigen alleles and haplotypes implicated in psoriatic arthritis susceptibility and their location within the major histocompatibility complexAllelesAncestral extended
rheumatoid arthritis 5679 alleles, were shown to predominate in PsA synovial fluid with a reversal of the CD4:CD8 ratio found in rheumatoid arthritis (RA) [[6]]. Thirdly, CD8+ T cells in synovial tissue and fluid obtained from PsA patients are clonally
sacroiliitis 2765 manifestations, including whether or not they exhibit dactylitis, enthesitis, asymmetric or symmetric sacroiliitis , or joint deformity, but also in the presence and type of joint damage on plain radiography. For example,
sacroiliitis 22321 delayed milder musculoskeletal disease with greatly reduced penetrance.Genetic influence on whether sacroiliitis is symmetrical or asymmetricalIn a follow up to the original genetic paper, 282 patients of the above
sacroiliitis 22967 two-tailed Pearson chi-square method [[2]].While ankylosing spondylitis is characterised by symmetrical sacroiliitis , in PsA sacroiliitis is more likely to be asymmetric [[33]]. Table 5 presents data on whether the finding
sacroiliitis 22988 chi-square method [[2]].While ankylosing spondylitis is characterised by symmetrical sacroiliitis, in PsA sacroiliitis is more likely to be asymmetric [[33]]. Table 5 presents data on whether the finding of symmetric or
sacroiliitis 23114 likely to be asymmetric [[33]]. Table 5 presents data on whether the finding of symmetric or asymmetric sacroiliitis by X-ray imaging is associated with an HLA genotype. The table shows that HLA-B*27:05:02 and both of
sacroiliitis 23285 table shows that HLA-B*27:05:02 and both of its haplotypes were strongly associated with symmetrical sacroiliitis . Symmetrical sacroiliitis and B*27:05 was male preponderant (odds ratio = 11.91), resembling the
sacroiliitis 23311 HLA-B*27:05:02 and both of its haplotypes were strongly associated with symmetrical sacroiliitis. Symmetrical sacroiliitis and B*27:05 was male preponderant (odds ratio = 11.91), resembling the findings in ankylosing spondylitis
sacroiliitis 23624 haplotypes (B*27:05-C*01:02 and B*27:05:02-C*02:02:01) were equivalently associated with symmetric sacroiliitis (Table 6).Table 5Frequency of human leukocyte antigen allele or haplotype in forms of sacroiliitisMarkerSacroiliitisSymmetrical
sacroiliitis 23724 sacroiliitis (Table 6).Table 5Frequency of human leukocyte antigen allele or haplotype in forms of sacroiliitis MarkerSacroiliitisSymmetrical sacroiliitisAsymmetrical sacroiliitisB*08:0150.70%16.70%62.70% P value0.0060.066<0.000 OR
sacroiliitis 23766 of human leukocyte antigen allele or haplotype in forms of sacroiliitisMarkerSacroiliitisSymmetrical sacroiliitis Asymmetrical sacroiliitisB*08:0150.70%16.70%62.70% P value0.0060.066<0.000 OR (95% CI)2.15 (1.06
sacroiliitis 23791 allele or haplotype in forms of sacroiliitisMarkerSacroiliitisSymmetrical sacroiliitisAsymmetrical sacroiliitis B*08:0150.70%16.70%62.70% P value0.0060.066<0.000 OR (95% CI)2.15 (1.06 to 1.77)0.323 (0.91 to 1.143)3.8
sacroiliitis 25254 value0.213 OR (95% CI)1.80 (0.71 to 4.59)CI, confidence interval; OR, odds ratio.In contrast, asymmetric sacroiliitis , the more prevalent form of sacroiliitis in PsA, was not significantly associated with B*27:05 but,
sacroiliitis 25295 confidence interval; OR, odds ratio.In contrast, asymmetric sacroiliitis, the more prevalent form of sacroiliitis in PsA, was not significantly associated with B*27:05 but, rather, exhibited a strong association with
sacroiliitis 25550 haplotype and its constituent alleles. As a rough estimate of the effect of these two haplotypes on the sacroiliitis phenotype, 24.4% of those bearing B*27:05:02 developed symmetric sacroiliitis and 11.1% asymmetric sacroiliitis,
sacroiliitis 25628 two haplotypes on the sacroiliitis phenotype, 24.4% of those bearing B*27:05:02 developed symmetric sacroiliitis and 11.1% asymmetric sacroiliitis, while 2.9% of those with B*08:01 developed symmetric sacroiliitis
sacroiliitis 25662 phenotype, 24.4% of those bearing B*27:05:02 developed symmetric sacroiliitis and 11.1% asymmetric sacroiliitis , while 2.9% of those with B*08:01 developed symmetric sacroiliitis and 30.8% asymmetric sacroiliitis.Human
sacroiliitis 25729 sacroiliitis and 11.1% asymmetric sacroiliitis, while 2.9% of those with B*08:01 developed symmetric sacroiliitis and 30.8% asymmetric sacroiliitis.Human leukocyte antigen associations of enthesitisEnthesitis is often
sacroiliitis 25763 sacroiliitis, while 2.9% of those with B*08:01 developed symmetric sacroiliitis and 30.8% asymmetric sacroiliitis .Human leukocyte antigen associations of enthesitisEnthesitis is often a striking feature of PsA. McGonagle
sacroiliitis 30325 considered would denote a more severely involved patient, including enthesitis, symmetric or asymmetric sacroiliitis , dactylitis, joint deformity, joint erosion, joint fusion or osteolysis [[2]]. This score was used to
sacroiliitis 36055 whether you have HLA-B*27:05 or HLA-B*08:01 will determine whether you have symmetrical or asymmetrical sacroiliitis or whether you have a disease that is more axial or entheseal predominant, or perhaps more synovial
spondylitis 13484 individuals presenting to a dermatologic clinic who were determined to be without features of arthritis, spondylitis or enthesitis through examination by a rheumatologist. This cohort was compared with a PsA cohort (n = 359)
spondylitis 22923 clinical characteristics using the asymmetric two-tailed Pearson chi-square method [[2]].While ankylosing spondylitis is characterised by symmetrical sacroiliitis, in PsA sacroiliitis is more likely to be asymmetric [[33]].
spondylitis 23422 sacroiliitis and B*27:05 was male preponderant (odds ratio = 11.91), resembling the findings in ankylosing spondylitis and supporting current endeavours to group the axial spondyloarthritis together. Both B*27 haplotypes
spondylitis 34407 inflammatory pathways will be more analogous to those in PsO, while others may resemble those of ankylosing spondylitis .It is interesting to note that the newer genetic findings are consistent with and appear to provide
spondylitis 38416 with more severe axial bone marrow oedema on MRI that is probably related to the classic ankylosing spondylitis phenotype, while HLA-B27-negative PsA was likely to be reported as a negative MRI examination result.Figure
synovitis 9343 for the development of concepts that link entheseal involvement with prominent features of PsA, both synovitis and nail dystrophic change. Furthermore, magnetic resonance imaging (MRI) studies have highlighted bone
synovitis 28940 complexity of the process occurring in dactylitis [[35]-[37]], including varying contributions of flexor teno synovitis , synovitis, enthesitis and more circumferential soft tissue oedema. It would be of interest to determine
synovitis 28951 process occurring in dactylitis [[35]-[37]], including varying contributions of flexor tenosynovitis, synovitis , enthesitis and more circumferential soft tissue oedema. It would be of interest to determine whether
synovitis 29225 alleles resulted in subgrouping patients with different types of digital processes (for example, teno synovitis /synovitis vs. enthesitis).Table 7Dactylitis is associated with bothHLA-B*27:05andB*08:01,but notHLA-C*06:02HLA
synovitis 29235 resulted in subgrouping patients with different types of digital processes (for example, tenosynovitis/ synovitis vs. enthesitis).Table 7Dactylitis is associated with bothHLA-B*27:05andB*08:01,but notHLA-C*06:02HLA
synovitis 40486 propose a testable hypothesis whereby PsA can be considered to have at least four clinical phenotypes – synovitis predominant, entheseal predominant, axial predominant and mutilans – all determined by genotype. In
tenosynovitis 28936 complexity of the process occurring in dactylitis [[35]-[37]], including varying contributions of flexor tenosynovitis , synovitis, enthesitis and more circumferential soft tissue oedema. It would be of interest to determine
tenosynovitis 29221 susceptibility alleles resulted in subgrouping patients with different types of digital processes (for example, tenosynovitis /synovitis vs. enthesitis).Table 7Dactylitis is associated with bothHLA-B*27:05andB*08:01,but notHLA-C*06:02HLA

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