Prognostic markers of radiographic progression in early rheumatoid arthritis.
OBJECTIVE
To identify prognostic markers that are predictive of progressive erosive disease in patients with early rheumatoid arthritis (RA).


METHODS
The study involved an inception cohort of 111 consecutive patients with RA and a disease duration of <1 year. Patients were treated according to an algorithm designed to avoid overtreatment of mild disease and to accelerate treatment in patients who had continuous disease activity. Patients were evaluated for the presence of clinical and laboratory disease activity markers. We determined the frequency of CD4+,CD28(null) T cells by flow cytometry, HLA-DRB1 gene polymorphisms by polymerase chain reaction (PCR)/sequencing, and 26 single-nucleotide polymorphisms in 19 candidate genes by multiplex PCR and hybridization to an immobilized probe array. Data were analyzed using proportional odds models to identify prognostic markers predictive of erosive progression over 2 years on serial hand/wrist radiographs.


RESULTS
After 2 years, disease activity in 52% of the cohort was controlled by treatment with hydroxychloroquine and nonsteroidal agents. Forty-eight percent of the patients did not develop erosions. Older age, presence of erosions at baseline, presence of rheumatoid factor, rheumatoid factor titer, and HLA-DRB1*04 alleles, particularly homozygosity for HLA-DRB1*04, were univariate predictors of radiographic progression. Promising novel markers were the frequency of CD4+,CD28(null) T cells as an immunosenescence indicator, and a polymorphism in the uteroglobin gene.


CONCLUSIONS
Clinical disease activity in patients with early RA can frequently be controlled with nonaggressive treatment, but this is not always sufficient to prevent new erosions. Rheumatoid factor titer, HLA-DRB1 polymorphisms, age, and immunosenescence markers are predictors of poor radiographic outcome. A polymorphism in the uteroglobin gene may identify patients who have a low risk of erosive disease.
Goronzy
Jörg J
JJ
Mayo Clinic, Rochester, Minnesota 55905, USA. goronzy.jorg@mayo.edu
Matteson
Eric L
EL
Fulbright
James W
JW
Warrington
Kenneth J
KJ
Chang-Miller
April
A
Hunder
Gene G
GG
Mason
Thomas G
TG
Nelson
Audrey M
AM
Valente
Robert M
RM
Crowson
Cynthia S
CS
Erlich
Henry A
HA
Reynolds
Rebecca L
RL
Swee
Ronald G
RG
O'Fallon
W Michael
WM
Weyand
Cornelia M
CM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011859:Radiography; D012217:Rheumatoid Factor / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology; D014955:Wrist Joint / Q000000981:diagnostic imaging
D018501:Antirheumatic Agents; D015415:Biomarkers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D012217:Rheumatoid Factor