HLA‐B27 haplotypes in family studies of ankylosing spondylitis

Lochead, J A; Chalmers, Ian; Marshall, William H.; Larsen, Bodil; Skanes, Verna M.; Payne, R. H.; Barnard, John M.

doi:10.1002/art.1780260810

Cited by 34 publications

(11 citation statements)

References 15 publications

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“…00072) in which the proband is homozygous for B27 and all other members express the B27 phenotype, the fragment is absent in the proband's sister; this indicates that the 9.2-kb fragment does not segregate with all B27-containing haplotypes. This observation is of interest in regard to the hypothesis that HLA haplotypes carrying the B27 and AS gene(s) might be different from the haplotype which contains B27 but lacks the AS gene (26). Although in the other AS family studied (no.…”

Section: Mcdaniel Et Almentioning

confidence: 89%

Association of a 9.2‐kilobase pvu ii class i major histocompatibility complex restriction fragment length polymorphism with ankylosing spondylitis

McDaniel

Acton

Barger

et al. 1987

Arthritis & Rheumatism

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We analyzed DNA restriction fragment length polymorphism (RFLP) in 53 white ankylosing spondylitis (AS) patients and 92 healthy controls, utilizing a full-length HLA-B7 complementary DNA probe. A 9.2-kilobase (kb) Pvu I1 fragment was found to be significantly increasexn frequency in B27 positive AS patients compared with the B27 positive control group (P = 0.00085, relative risk = 7.2). The presence of both B27 and the 9.2-kb RFLP in an individual conferred a relative risk for AS of 297, compared with a relative risk of 119 in those who had B27 alone. The 9.2-kb RFLP appears to be a marker for AS which, with HLA-B27, contributes further to susceptibility to the disease. Our The seronegative spondylarthropathies, including ankylosing spondylitis (AS), Reiter's syndrome, psoriatic arthritis/spondylitis, and the arthritidspondylitis of inflammatory bowel disease, constitute a heterogeneous group of disorders characterized by axial and/or peripheral arthritis, overlapping clinical features, a tendency toward familial aggregation, and the absence of rheumatoid factor or subcutaneous nodules (1). Although the association of AS and other seronegative spondylarthropathies with HLA-B27 is well documented (2,3), the precise role of B27 in the genetic susceptibility to AS is yet to be established. There is a marked discrepancy between the frequency of this antigen in the white population (6.8%) and the prevalence of AS (0.2%), which raises the possibility that a unique subtype of B27 or a linked gene might be more disease-specific. As many as 6 B27 subtypes have been identified by a combination of approaches, including monoclonal antibody studies (4), cytotoxic T lymphocyte studies (5,6), a restriction typing assay (7), high performance liquid chromatography peptide mapping @), and amino acid and nucleotide sequencing (9,lO). Different B27 variants have exhibited higher or lower prevalence according to ethnic group (1 1,12).The availability of complementary DNA (cDNA) probes specific for the class I major histocompatibility complex (MHC) region genes permits further definition of these genes at the DNA level. A useful approach in this regard has been the technique of restriction fragment length polymorphism (RFLP)

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Section: Mcdaniel Et Almentioning

confidence: 89%

Association of a 9.2‐kilobase pvu ii class i major histocompatibility complex restriction fragment length polymorphism with ankylosing spondylitis

McDaniel

Acton

Barger

et al. 1987

Arthritis & Rheumatism

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“…However, we could not show any association with a particular chromosome 6 haplotype. Some years ago Lochead studied the frequencies of particular haplotypes in this region of chromosome 6 in 18 B27 + AS + families and compared them to the distribution of haplotypes in 19 HLA-B27 + control families [7]. He showed an equal HLA-B27 § haplotype distribution in both family groups.…”

Section: Hla-b27 Subtypesmentioning

confidence: 99%

“…Therefore, other familial factors in addition to HLA-B27 must play a role in the susceptibility of AAU and AS. These factors are probably of genetic origin, since the observed data did not support the influences of environmental factors [6,7].…”

Section: Introductionmentioning

confidence: 99%

Acute anterior uveitis and HLA-B27

Derhaag

Feltkamp

1990

Int Ophthalmol

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All studies among acute anterior uveitis patients (AAU) agree on the importance of and high association with HLA-B27. However, the majority of the HLA-B27+ population will never develop AAU. The partial association of AAU and HLA-B27 is probably not based on a preferential association with a particular B27 subtype, since the HLA-B27 subtypes are equally distributed among normal controls and AAU patients. Therefore, other factors increase the susceptibility to HLA-B27 associated diseases. Family investigations among the relatives of AAU and AS patients suggest the existence of other pathogenic genetic factors in addition to HLA-B27. Due to extensive research, associations with other genes on chromosome 6 could almost be excluded and associations with genes on other chromosomes were not yet found. The only reproducible association between AAU and any genes or gene products is, at the moment, still the association with HLA-B27. However, its role, which most probably is functional, is far from clear.

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“…The fact that -80% of B27-positive individuals never develop AS [14] led investigators to focus on the possibility that there are two different HLA-B27 molecules. If a difference could be identified between normal and disease HLA-B27, it may explain why only some B27-positive patients develop AS.…”

Section: Hla-b27 Exists In Both a Pathogenic And A Benignmentioning

confidence: 99%

HLA‐B27: What is its role in the development of ankylosing spondylitis?

Cromwell

Baron

1990

Arthritis & Rheumatism

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Although the association between HLA‐B27 and ankylosing spondylitis (AS) is well established, the mechanism governing this association remains unknown. Although ∼90% of affected individuals possess the HLA‐B27 antigen, HLA‐B27 is also present in ∼8% of the normal population. This article examines the association by reviewing recent literature. Theories proposed have ranged from HLA‐B27's possible role as a marker for an AS susceptibility gene to the possibility of HLA‐B27 being a direct contributor to disease. Theories suggest the presence of pathogenic and benign forms of the antigen, as well as interaction with genetic and environmental factors in disease development. Recent investigations have focused on a link with Klebsiella and its role in a “cross‐reactive” mechanism with HLA‐B27 in AS development. Studies to date have not provided conclusive evidence on the exact mechanism by which HLA‐B27 predisposes individuals to the development of disease. The importance of isolating a specific causative agent for AS is discussed.

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HLA‐B27 haplotypes in family studies of ankylosing spondylitis

Cited by 34 publications

References 15 publications

Association of a 9.2‐kilobase pvu ii class i major histocompatibility complex restriction fragment length polymorphism with ankylosing spondylitis

Association of a 9.2‐kilobase pvu ii class i major histocompatibility complex restriction fragment length polymorphism with ankylosing spondylitis

Acute anterior uveitis and HLA-B27

HLA‐B27: What is its role in the development of ankylosing spondylitis?

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