HLA markers for susceptibility and expression in scleroderma.
OBJECTIVE
Reported associations between HLA alleles and both susceptibility to and features of scleroderma have been conflicting. Our objective was (1) to determine the role of HLA alleles in the susceptibility to scleroderma; and (2) to determine the role of HLA alleles in various aspects of disease expression.


METHODS
Consecutive patients were followed in the scleroderma clinic between 1996 and 1998. Clinical data were obtained through chart review. Healthy volunteers as well as cadaveric donors served as controls. Molecular HLA typing was performed (polymerase chain reaction/sequence-specific oligonucleotides). Statistical analysis included Fisher's exact test and multivariate analyses, using logistic and linear regression models.


RESULTS
Ninety-five Caucasian patients (75 women, 20 men, age 43.9 yrs, disease duration 11.9 yrs) with scleroderma and 416 controls were studied. HLA-DRB1*01 and HLA-DRB1*11 were associated with susceptibility to scleroderma, whereas HLA-DRB1*07 was protective. HLA-A*30 and HLA-A*32 were also associated with susceptibility to scleroderma, while HLA-B*57 and HLA-Cw*14 were protective. HLA-B*62 and HLA-DRB1*07 had a significant correlation with the presence of diffuse skin involvement in both univariate and multivariate analyses. HLA-DRB1*11 was associated with high skin score values, while lower values were related to the presence of HLA-Cw*14 and HLA-DQB1*06. Both alleles retained significance in a linear regression model. High skin score values were related to the absence of anticentromere antibodies. Pulmonary fibrosis was associated with HLA-B*62 and HLA-Cw*0602, whereas pulmonary hypertension was associated with HLA-B*13 and HLA-B*65.


CONCLUSIONS
HLA alleles play a role in susceptibility to scleroderma and its disease expression.
Gladman
Dafna D
DD
Centre for Prognosis Studies in the Rheumatic Diseases, University Health Network, Toronto Western Hospital, Ontario, Canada. dafna.gladman@utoronto.ca
Kung
Tabitha N
TN
Siannis
Fotios
F
Pellett
Fawnda
F
Farewell
Vernon T
VT
Lee
Peter
P
D000328:Adult; D000368:Aged; D000483:Alleles; D015415:Biomarkers; D004198:Disease Susceptibility / Q000453:epidemiology / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000276:immunology / Q000401:mortality; D015994:Incidence; D008297:Male; D008875:Middle Aged; D045743:Scleroderma, Diffuse / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D045745:Scleroderma, Limited / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D015996:Survival Rate
D015415:Biomarkers; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains