B*27 in molecular diagnostics: Impact of new alleles and polymorphism outside exons 2 and 3

Human leukocyte antigen (HLA)-B27 is closely associated with ankylosing spondylitis (AS). However, the exact correlation between HLA-B27 subtypes and AS manifestations remains unknown. This study aimed to investigate the correlation between HLA-B27 polymorphism and the clinical features of AS. This study included 846 patients with AS and 959 healthy controls. Direct sequencing was used to identify the HLA-B27 genotype. Clinical parameters, including age, age of onset, family history, low back pain, peripheral arthritis, hip joint involvement, dactylitis, uveitis, and sex ratio, were compared among patients with various HLA-B27 subtypes. In total, 741 AS patients (87.6%) and 39 healthy controls (4%) were HLA-B27-positive. The most prevalent subtypes were HLA-B*2704 (88%) and HLA-B*2705 (10.1%) in patients with AS. Compared with HLA-B*2704-positive patients, HLA-B*2705-positive patients demonstrated a significant increase in the incidence of uveitis (16% vs 6.13%, P = 0.002) and dactylitis (9.3% vs 3.8%, P = 0.028) and they had an older age of onset (22.9 ± 8.0 vs 20.7 ± 6.7 years, P = 0.028). Binary logistic regression analysis revealed that presence of uveitis was significantly associated with HLA-B*2705 (P = 0.008; odds ratio, 2.63; 95% confidence interval, 1.283-5.393). There were no significant differences in family history, low back pain, peripheral arthritis, or hip joint involvement among HLA-B27 subtypes. Specific HLA-B27 subtypes were positively associated with particular clinical features of AS. AS patients with HLA-B*2705 demonstrated an older age of onset and had a higher risk of uveitis and dactylitis than did AS patients with HLA-B*2704.

Section: Discussionmentioning

confidence: 99%

Higher risk of uveitis and dactylitis and older age of onset among ankylosing spondylitis patients with HLA‐B2705* than patients with HLA‐B2704* in the Chinese population

Liao

et al. 2013

“…Unlike the situation in many Caucasian populations where B*2705 is largely predominant, populations in Eastern Asia, particularly in China, show a prevalence of the AS‐associated subtype B*2704, while still showing a significant frequency of B*2705. Moreover, B*2704 appears to be the ancestor of a group of less frequent subtypes found in East Asian populations, including B*2715, which differs from B*2704 by a single amino acid change at position 163 (10).…”

Section: Human Leukocyte Antigen (Hla)‐b27 Subtypes and Ankylosing Spmentioning

confidence: 99%

HLA‐B27 and ankylosing spondylitis: tales from China

Castro

2009

The two most frequent HLA-B27 subtypes worldwide are B*2704 and B*2705. In the Han population of China B*2704 and, to a lower extent, B*2705 are found with significant frequency, and both are associated to ankylosing spondylitis (AS). Two articles in this issue report that the association to AS in this ethnic group is stronger for B*2704 than for B*2705. Thus, at least among the Han, B*2704 would be the strongest known susceptibility factor for AS.

“…If this did not result in an allele typing to the four-digit level at the time of analysis, additional exons and/or allele-specific sequencing was performed until an unequivocal four-digit typing result was obtained. Additional exons 1 and 4 for HLA-A and 1, 4 and 5 for HLA-B and -Cw were sequenced using amplification primers located in the adjacent introns as described (4,(9)(10)(11)(12)(13)(14). For allele-specific sequencing, in-house custom group-specific amplification primers were used (4,(15)(16)(17)(18)(19)(20)(21).…”

Section: Sequence-based Typingmentioning

confidence: 99%

Reanalysis of sequence‐based HLA‐A, ‐B and ‐Cw typings: how ambiguous is today’s SBT typing tomorrow

Voorter¹,

Mulkers²,

Liebelt³

et al. 2007

The permanently increasing number of human leukocyte antigen (HLA)-alleles and the growing list of ambiguities require continuous updating of high-resolution HLA typing results. Two different kinds of ambiguities exist: the first, when two or more allele combinations have identical heterozygous sequences, and the second, when differences are located outside the analyzed region. The number of HLA-A, B and C alleles recognized in 1999 was almost tripled in 2006. Two hundred individuals, sequence-based typing (SBT) typed in the period from 1999 to 2002, were reanalyzed using the 2006 database. A final allele typing result of at least four digits was obtained for HLA-A, -B and -C by heterozygous sequencing of exons 2 and 3 and, if necessary, additional exons and/or allele-specific sequencing. Storage of the individual sequences in a specially developed database enabled reanalysis with all present and future HLA releases. In the 5-year period HLA-A, -B and -C typing results became ambiguous in 37%, 46% and 41% of the cases. Most were because of differences outside the analyzed region; ambiguities because of different allele combinations with identical heterozygous sequences were present in 7%, 8% and 13% of the HLA-A, -B and -C typings. These results indicate that within 5 years, approximately half of the HLA SBT typings become ambiguous.