HLA-Bw60 increases susceptibility to ankylosing spondylitis in HLA-B27+ patients.

We examined the distribution of non-B27 alleles of the HLA-B locus among B27+ patients with ankylosing spondylitis (AS), to detect any additional HLA-B locus allele(s) that may act in conjunction with B27 to increase susceptibility to AS. HLA-Bw60 (or B40 when the Bw60,61 split of B40 was not typed for) was shown to be increased among B27+ AS patients in each of 5 independent data sets. This increase was statistically significant in 4 of the 5 data sets studied, and the overall significance was P less than 0.00001. Susceptibility to AS in B27+ individuals was further increased by a factor of approximately 3 when Bw60 was also present. The distribution of HLA-A alleles on the B27-bearing haplotypes in AS patients was not significantly different from that in normal controls. On the other hand, the distribution of HLA-A alleles on Bw60-bearing haplotypes was significantly different from the distribution of A alleles on Bw60 haplotypes in the general population (P less than 0.0005). Bw60 was not increased in B27- patients with AS. A dominant mode of inheritance generally fits AS; however, our sib pair analysis indicates that the B27,Bw60 disease subgroup follows a more recessive mode of inheritance.

[1]  M. Khan.  Ankylosing spondylitis and heterogeneity of HLA-B27. , 1988, Seminars in arthritis and rheumatism.

[2]  P. Tugwell,et al.  Chest pain without radiographic sacroiliitis in relatives of patients with ankylosing spondylitis. , 1988, The Journal of rheumatology.

[3]  G. Thomson.  HLA disease associations: models for insulin dependent diabetes mellitus and the study of complex human genetic disorders. , 1988, Annual review of genetics.

[4]  K. Bauer.  Evidence for a protective influence of blood group A phenotype on X-ray signs of ankylosing spondylitis in HLA-B27 positives. , 1987, Disease markers.

[5]  D. Jaraquemada,et al.  Fine specificity of HLA-B27 cellular allorecognition. HLA-B27f is a functional variant distinguishable by cytolytic T cell clones. , 1987, Journal of immunology.

[6]  C. Falk,et al.  Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations , 1987, Annals of human genetics.

[7]  J. Rotés-Querol,et al.  HLA class II antigens (DR, DQ loci) and peripheral arthritis in ankylosing spondylitis. , 1987, Annals of the rheumatic diseases.

[8]  P. Iványi,et al.  Distribution of HLA-B27 subtypes in patients with ankylosing spondylitis: the disease is associated with a common determinant of the various B27 molecules. , 1987, Annals of the rheumatic diseases.

[9]  E. Louis,et al.  Three-Allele Synergistic Mixed Model for Insulin-Dependent Diabetes Mellitus , 1986, Diabetes.

[10]  M. Baur,et al.  HLA‐DR effects in a large German IDDM dataset , 1986, Genetic epidemiology. Supplement.

[11]  G. Thomson,et al.  The affected sib method. I. Statistical features of the affected sib-pair method. , 1985, Genetics.

[12]  D. Glass,et al.  Complementation with HLA-A and HLA-D locus alleles in ankylosing spondylitis with peripheral arthritis. , 1985, The Journal of rheumatology.

[13]  J. Gran,et al.  Prevalence of ankylosing spondylitis in males and females in a young middle-aged population of Tromsø, northern Norway. , 1985, Annals of the rheumatic diseases.

[14]  W. Miehle,et al.  HLA-DR4 in ankylosing spondylitis with different patterns of joint involvement. , 1985, Annals of the rheumatic diseases.

[15]  S. M. van der Linden,et al.  The risk of ankylosing spondylitis in HLA-B27 positive individuals: a reappraisal. , 1984, The Journal of rheumatology.

[16]  Russell As,et al.  The risk of sacroiliitis in B27 positive persons: a reappraisal. , 1984 .

[17]  B. M. Jongh,et al.  The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. , 1984, Arthritis and rheumatism.

[18]  G. Thomson.  Investigation of the mode of inheritance of the HLA associated diseases by the method of antigen genotype frequencies among diseased individuals. , 2008, Tissue antigens.

[19]  A Calin,et al.  Genetic differences between B27 positive patients with ankylosing spondylitis and B27 positive healthy controls. , 1983, Arthritis and rheumatism.

[20]  P. Møller,et al.  Family studies in Bechterew's syndrome (ankylosing spondylitis) III. Genetics , 1983, Clinical genetics.

[21]  J. D'Amaro,et al.  HLA AND REPRODUCTION? , 1983, Journal of immunogenetics.

[22]  M. Khan.  B7-CREG and ankylosing spondylitis. , 1983, British Journal of Rheumatology.

[23]  K. Berg,et al.  The distribution of clinical findings in Bechterew's syndrome (ankylosing spondylitis) suggests distinct genetic subgroups , 1982, Clinical genetics.

[24]  W. Braun,et al.  Genetic heterogeneity in primary ankylosing spondylitis. , 1980, The Journal of rheumatology.

[25]  R D Sturrock,et al.  Ankylosing spondylitis and HL-A 27. , 1973, Lancet.

[26]  P I Terasaki,et al.  High association of an HL-A antigen, W27, with ankylosing spondylitis. , 1973, The New England journal of medicine.