title: DRB1*15 allele is a risk factor for PR3-ANCA disease in African Americans.
abstract: Anti-neutrophil cytoplasmic autoantibody (ANCA) disease rarely occurs in African Americans and risk factors for the disease in this population are unknown. Here, we genotyped MHC class II alleles and found that, among African Americans, those with proteinase 3-ANCA (PR3-ANCA) had 73.3-fold higher odds of having HLA-DRB1*15 alleles than community-based controls (OR 73.3; 95% CI 9.1 to 591). In addition, a disproportionate number of African American patients carried the DRB1*1501 allelic variant of Caucasian descent rather than the DRB1*1503 allelic variant of African descent. Among Caucasians, those with PR3-ANCA had 2.2-fold higher odds of carrying DRB1*1501 than controls (OR 2.2; 95% CI 1.2 to 4.0). A validation study supported by the Vasculitis Clinical Research Consortium confirmed the strong association between the DRB1*15 allele and PR3-ANCA disease, among African Americans. Furthermore, we found that DRB1*1501 protein binds with high affinity to amino acid sequences of sense-PR3, purportedly an antigenic epitope, and to the amino acid sequence complementary to this epitope in vitro. Peptides of sense-PR3 and complementary-PR3 also bound to TNF-α-induced surface expression of DRB1*1501 on peripheral neutrophils. Taken together, these data suggest HLA-DRB1*15 alleles contribute to the pathogenesis of PR3-ANCA disease.
authors: UNC Kidney Center, Department of Medicine, Division of Nephrology and Hypertension, Chapel Hill, NC 27599, USA.
authors: Yali
authors: Y
authors: Cao
authors: John L
authors: JL
authors: Schmitz
authors: Jiajin
authors: J
authors: Yang
authors: Susan L
authors: SL
authors: Hogan
authors: Donna
authors: D
authors: Bunch
authors: Yichun
authors: Y
authors: Hu
authors: Caroline E
authors: CE
authors: Jennette
authors: Elisabeth A
authors: EA
authors: Berg
authors: Frank C
authors: FC
authors: Arnett
authors: J Charles
authors: JC
authors: Jennette
authors: Ronald J
authors: RJ
authors: Falk
authors: Gloria A
authors: GA
authors: Preston
references: Kidney Int. 2008 Nov;74(9):1159-69
references: 18596726
references: Kidney Int. 2001 Dec;60(6):2247-62
references: 11737598
references: Nat Med. 2004 Jan;10(1):72-9
references: 14661018
references: J Immunol. 1993 Aug 1;151(3):1482-90
references: 8335942
references: Am J Hum Genet. 1989 Oct;45(4):541-6
references: 2491013
references: Ann Intern Med. 2005 Nov 1;143(9):621-31
references: 16263884
references: J Rheumatol. 2003 Mar;30(3):618-21
references: 12610825
references: Kidney Int. 1999 May;55(5):1811-8
references: 10231443
references: Am J Kidney Dis. 1999 Aug;34(2):364-73
references: 10430990
references: J Exp Med. 1998 Apr 6;187(7):1019-28
references: 9529318
references: Arthritis Rheum. 2008 Sep;58(9):2908-18
references: 18759282
references: Immunogenetics. 1995;41(4):178-228
references: 7890324
references: Clin Exp Immunol. 2001 Jan;123(1):170-7
references: 11168015
references: Ann Rheum Dis. 1986 May;45(5):417-21
references: 3718017
references: Kidney Int. 1992 Apr;41(4):1059-63
references: 1381003
references: Intern Med J. 2007 Apr;37(4):242-6
references: 17388864
references: Arthritis Rheum. 2004 Feb 15;51(1):92-9
references: 14872461
references: PLoS Comput Biol. 2008 Apr 04;4(4):e1000048
references: 18389056
references: Br J Rheumatol. 1991 Apr;30(2):144-5
references: 2012946
references: J Am Soc Nephrol. 1996 Jan;7(1):23-32
references: 8808106
references: J Am Soc Nephrol. 1996 Jan;7(1):33-9
references: 8808107
references: J Immunol. 1994 May 1;152(9):4722-37
references: 8157982
references: Genes Immun. 2003 Jun;4(4):316-20
references: 12761569
references: Immunology. 2006 Dec;119(4):562-71
references: 17034427
references: Arthritis Rheum. 1983 Jan;26(1):102-5
references: 6130772
references: Tissue Antigens. 2003 Mar;61(3):249-52
references: 12694574
references: Kidney Int. 2001 Jan;59(1):147-59
references: 11135067