HLA allelic variants encoding DR11 in diffuse and limited systemic sclerosis in Caucasian women

Rheumatology (Oxford). 2005 Mar;44(3):318-22. doi: 10.1093/rheumatology/keh489. Epub 2004 Nov 30.


Objective: We investigated HLA class II alleles in women with systemic sclerosis (SSc), a rare disease that preferentially affects women.

Methods: Specific alleles of DRB1, DQA1 and DQB1 were determined by DNA-based HLA typing for women with SSc (n = 102) and healthy women (n = 533). All study subjects were Caucasian. DRB1, DQA1 and DQB1 allele frequencies of women with SSc were compared with those of healthy women.

Results: Among women with SSc, 29.4% (30/102) and among healthy women 10.7% (57/533) had DRB1*11. Allele frequencies were compared for women with SSc and healthy women (each woman has two alleles). The allele frequency of DRB1*11 was 15.7% (32/204 alleles) in SSc women and 5.8% (62/1066 alleles) in healthy women (P = 0.000002). The increase of DRB1*11 was found both in diffuse (P = 0.0001) and limited SSc (P = 0.002) (allele frequencies 15.0 and 17.2%, respectively). Among women with diffuse SSc, there was a disproportionate increase of the DRB1*1104 allele (P = 0.0004) with no increase of DRB1*1101 (P = 1.00). In contrast, in limited SSc the strongest association was with DRB1*1101 (P = 0.008), with a less significant increase of DRB1*1104 (P = 0.04).

Conclusions: An increase of DRB1*11 in SSc is consistent with other reports. Although present in both diffuse and limited SSc disease subsets, the increase was predominantly due to over-representation of DRB1*1104 in women with diffuse SSc. Women with limited SSc had a preponderance of DRB1*1101, the most common allele in healthy women. DRB1*1104 and DRB1*1101 differ by a single amino acid at position 86, where the former has valine and the latter glycine.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Female
  • Gene Frequency
  • HLA-DQ Antigens / genetics
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class II / genetics*
  • Humans
  • Linkage Disequilibrium
  • Middle Aged
  • Scleroderma, Diffuse / genetics
  • Scleroderma, Limited / genetics
  • Scleroderma, Systemic / genetics*


  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class II