PMID- 10648455
OWN - NLM
STAT- MEDLINE
DCOM- 20000224
LR  - 20190707
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 118
IP  - 2
DP  - 2000 Feb
TI  - Clinical phenotype is related to HLA genotype in the peripheral arthropathies of 
      inflammatory bowel disease.
PG  - 274-8
AB  - BACKGROUND & AIMS: The detection of phenotype-determining genes as opposed to
      disease susceptibility genes requires precise phenotypic characterization of
      patients. Peripheral arthropathies in inflammatory bowel disease (IBD) are well
      recognized and are classified with the HLA-B*27-related spondyloarthropathies by 
      the European Spondyloarthropathy Study Group. However, previous HLA studies in
      IBD have only shown this association with axial disease rather than peripheral
      arthropathy. We recently reported a clinical classification that describes 2
      types of peripheral arthropathy, distinguished by their natural history and
      articular distribution. We now report the results of immunogenetic studies in
      these patients and compare them with other spondyloarthropathies. METHODS: IBD
      patients with type 1 (n = 57) and type 2 (n = 45) peripheral arthropathy were
      identified by case note review and questionnaire. Patients and 603 controls from 
      Oxfordshire were assigned HLA-A, -B, -C, -DR, and -DQ genotypes by
      sequence-specific primer polymerase chain reaction. Patient results were compared
      with controls (corrected for multiple comparisons), then with each other in light
      of existing hypotheses. The results were compared with those of a cohort of 30
      patients with postenteric reactive arthritis (ReA) and 16 patients with
      IBD-associated ankylosing spondylitis (IBD-AS). RESULTS: Type 1 arthropathy was
      associated with HLA-DRB1*0103 (DR103; a rare subtype of DR1) in 33% (P < 0.0001; 
      relative risk [RR], 12.1), B*35 in 30% (P = 0.01; RR, 2.2), and B*27 in 26% (P = 
      0. 001; RR, 4.0). In contrast, type 2 was associated with HLA-B*44 in 62% (P =
      0.01; RR, 2.1). Similar significant associations to type 1 arthropathy were found
      in ReA, except that the HLA-B*27 association was significantly stronger and an
      association was found with DRB1*0101 (DR1) in 43% (P = 0.001; RR, 2.2). IBD-AS
      was associated only with HLA-B*27 and DRB1*0101. CONCLUSIONS: These data suggest 
      that the clinical classification into type 1 and type 2 arthropathies describes
      immunogenetically distinct entities and establish that in polygenic disorders,
      genes may determine clinical phenotype without conferring overall disease
      susceptibility (in this case, HLA genes). Type 1 arthropathy is clinically and
      immunogenetically similar to the spondyloarthropathies, but different HLA
      associations may define phenotypically distinct groups. Type 2 arthropathy has
      different HLA associations and may have a different etiology. Further studies are
      now required to confirm these associations and to elucidate the different
      pathogenetic mechanisms.
FAU - Orchard, T R
AU  - Orchard TR
AD  - Gastroenterology Unit, University of Oxford, Radcliffe Infirmary, Oxford,
      England.
FAU - Thiyagaraja, S
AU  - Thiyagaraja S
FAU - Welsh, K I
AU  - Welsh KI
FAU - Wordsworth, B P
AU  - Wordsworth BP
FAU - Hill Gaston, J S
AU  - Hill Gaston JS
FAU - Jewell, D P
AU  - Jewell DP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-D Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - AIM
SB  - IM
MH  - Colitis, Ulcerative/genetics/immunology
MH  - Crohn Disease/genetics/immunology
MH  - Genetic Predisposition to Disease/genetics
MH  - Genotype
MH  - HLA-A Antigens/genetics
MH  - HLA-B Antigens/*genetics
MH  - HLA-C Antigens/genetics
MH  - HLA-D Antigens/genetics
MH  - HLA-DR Antigens/genetics
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Inflammatory Bowel Diseases/complications/*genetics/*immunology
MH  - Joint Diseases/*complications/genetics/immunology
MH  - *Major Histocompatibility Complex
MH  - Phenotype
MH  - Reference Values
EDAT- 2000/01/29 09:00
MHDA- 2000/02/26 09:00
CRDT- 2000/01/29 09:00
PHST- 2000/01/29 09:00 [pubmed]
PHST- 2000/02/26 09:00 [medline]
PHST- 2000/01/29 09:00 [entrez]
AID - S0016508500547453 [pii]
AID - 10.1016/s0016-5085(00)70209-5 [doi]
PST - ppublish
SO  - Gastroenterology. 2000 Feb;118(2):274-8. doi: 10.1016/s0016-5085(00)70209-5.