Associations of HLA-DRB and -DQB genes with two and five year outcome in rheumatoid arthritis

被引:99
作者
Eberhardt, K
Fex, E
Johnson, U
Wollheim, FA
机构
[1] Department of Rheumatology, Lund University Hospital
关键词
D O I
10.1136/ard.55.1.34
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective-To evaluate the clinical usefulness of genomic HLA typing during the first five years of established rheumatoid arthritis (RA). Methods-The HLA-DRB and -DQB alleles were determined by restriction length polymorphisms and polymerase chain reaction amplification with sequence specific primers in 99 Swedish patients with RA. Clinical features after two and five years disease duration were related to the genetic pattern. Seventy four patients were seropositive, 25 had nodules, 90 developed erosions, and 15 required joint replacements. Twelve patients were in remission after five years. Disability was assessed by health assessment questionnaire, and radiographic damage in hands and feet by the Larsen method. Results -Eighty seven per cent of the patients carried the conserved third hypervariable region sequence (HVR3), 32% had DRB1*04 on one allele, and 26% had DRB1*04 on both alleles (all frequencies significantly greater than in controls). Frequencies of DRB1*04 associated DQB*0301 and ''0302 were normal. Patients carrying DRB1*04 on both alleles tended to have more radiographic changes after two years, but this difference had diminished after five years. Disability did not vary with regard to the genotype. Homozygous HVR3 patients had about three times greater risk of undergoing joint replacement; Homozygosity for HVR3 and presence of DQB*0302 both tended to be associated with erosive disease. Conclusions-We confirmed a strong association ofdisease with the presence of the shared epitope on one or two alleles. However, genotype was not strongly associated with disease severity after two and five years disease duration, and thus the value of genomic typing to select patients for early aggressive therapy is questionable.
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页码:34 / 39
页数:6
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共 44 条
  • [1] RADIOGRAPHIC CHANGES IN EARLY RHEUMATOID DISEASE
    BROOK, A
    CORBETT, M
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 1977, 36 (01) : 71 - 73
  • [2] DQW7 AND THE C4B NULL ALLELE IN RHEUMATOID-ARTHRITIS AND FELTY SYNDROME
    CLARKSON, R
    BATE, AS
    GRENNAN, DM
    CHATTOPADHYAY, C
    SANDERS, P
    DAVIS, M
    KELLY, C
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 1990, 49 (12) : 976 - 979
  • [3] EARLY RHEUMATOID-ARTHRITIS - SOME SOCIAL, ECONOMICAL, AND PSYCHOLOGICAL-ASPECTS
    EBERHARDT, K
    LARSSON, BM
    NIVED, K
    [J]. SCANDINAVIAN JOURNAL OF RHEUMATOLOGY, 1993, 22 (03) : 119 - 123
  • [4] EBERHARDT K, 1993, J RHEUMATOL, V20, P1825
  • [5] HIP INVOLVEMENT IN EARLY RHEUMATOID-ARTHRITIS
    EBERHARDT, K
    FEX, E
    JOHNSSON, K
    GEBOREK, P
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 1995, 54 (01) : 45 - 48
  • [6] EARLY RHEUMATOID-ARTHRITIS - ONSET, COURSE, AND OUTCOME OVER 2 YEARS
    EBERHARDT, KB
    RYDGREN, LC
    PETTERSSON, H
    WOLLHEIM, FA
    [J]. RHEUMATOLOGY INTERNATIONAL, 1990, 10 (04) : 135 - 142
  • [7] ASSESSING DISABILITY IN PATIENTS WITH RHEUMATOID-ARTHRITIS - USE OF A SWEDISH VERSION OF THE STANFORD HEALTH ASSESSMENT QUESTIONNAIRE
    EKDAHL, C
    EBERHARDT, K
    ANDERSSON, SI
    SVENSSON, B
    [J]. SCANDINAVIAN JOURNAL OF RHEUMATOLOGY, 1988, 17 (04) : 263 - 271
  • [8] GENETIC TYPING OF PATIENTS WITH INFLAMMATORY ARTHRITIS AT PRESENTATION CAN BE USED TO PREDICT OUTCOME
    GOUGH, A
    FAINT, J
    SALMON, M
    HASSELL, A
    WORDSWORTH, P
    PILLING, D
    BIRLEY, A
    EMERY, P
    [J]. ARTHRITIS AND RHEUMATISM, 1994, 37 (08): : 1166 - 1170
  • [9] THE SHARED EPITOPE HYPOTHESIS - AN APPROACH TO UNDERSTANDING THE MOLECULAR-GENETICS OF SUSCEPTIBILITY TO RHEUMATOID-ARTHRITIS
    GREGERSEN, PK
    SILVER, J
    WINCHESTER, RJ
    [J]. ARTHRITIS AND RHEUMATISM, 1987, 30 (11): : 1205 - 1213
  • [10] MUTATIONS AND SELECTION IN THE GENERATION OF CLASS-II HISTOCOMPATIBILITY ANTIGEN POLYMORPHISM
    GUSTAFSSON, K
    WIMAN, K
    EMMOTH, E
    LARHAMMAR, D
    BOHME, J
    HYLDIGNIELSEN, JJ
    RONNE, H
    PETERSON, PA
    RASK, L
    [J]. EMBO JOURNAL, 1984, 3 (07) : 1655 - 1661