doi: 10.1111/j.1744-313X.2006.00629.x
© 2006 The Authors
Journal compilation © 2006 Blackwell Publishing Ltd, International Journal of Immunogenetics 33, 371– 373 371
Blackwell Publishing Ltd
A novel HLA-B*2730 allele found in a Slovene patient affected with
IgA nephropathy
B. Vidan-Jeras,* S. Kunilo,* I. Fae,† A. Kandus‡ & G. F. Fischer†
Summary
A novel allele HLA-B*2730 and the haplotype HLA-
A*03-B*2730-Cw*02-DRB1*16-DRB5 have been found
in a Slovene patient and his mother. The exon 2 sequence
is identical to that of HLA-B*2702, and the exon 3
sequence is identical to that of HLA-B*2719. A possible
mechanism for the generation of B*2730 is a gene con-
version event.
We describe a novel human leucocyte antigen (HLA)
allele officially named HLA-B*2730 (Marsh et al., 2005).
It was discovered in a 30-year-old man of Slovene origin
being on chronic haemodialysis treatment since August
2004. The novel allele and its corresponding haplotype
were also determined in the patient’s mother. The patient
developed end-stage renal disease as the consequence of
IgA nephropathy (IgAN), one of the most common
glomerulopathies in Caucasians (Nair & Walker, 2006).
Patients with IgAN are usually included in the waiting lists
of organ exchange organizations (Doxiadis et al., 2001).
To put the patient on the kidney waiting list, HLA class
I typing was performed by a standard complement-
dependent microcytotoxicity assay (CDC) using commer-
cial trays (Lymphotype HLA-ABC 144/2, Biotest, Dreieich,
Germany), followed by polymerase chain reaction (PCR)-
based amplification with sequence-specific primers (SSP)
for HLA-DRB loci (Olerup SSP HLA-DRB low resolution,
Genovision, Vienna, Austria). The patient appeared homo-
zygous for all tested loci; the phenotype was A3; B27;
Cw2; DRB1*16; DRB5. In order to rule out specificities
that could have been missed, the first typings were backed
up with additional PCR-SSP tests using the HLA-A, B, DR
low-resolution kit (Olerup SSP HLA-A-B-DR-Combi Tray,
Genovision, Vienna, Austria). While HLA-A and DR typings
were confirmed, HLA-B27 could not be undoubtedly
identified. Moreover, HLA-B27 high-resolution typing
with SSP (Olerup SSP HLA-B27, Genovision, Vienna, Aus-
tria) resulted in a reaction pattern that was not compatible
with any of the then known alleles, although many of the
primer pairs detected subgroups of B*27 alleles.
Concerted sequencing-based typings (SBT) of the HLA-
B locus were performed in two laboratories following two
different protocols, respectively. In both cases, both exon
2 and exon 3 were sequenced in two directions. The locus-
specific HLA-B Sequencing-Based-Typing Kit (Alle-
leSEQR HLA-B, Abbott, Chicago, IL) and correspond-
ing software (assign-sbt, Conexio Genomics,
Applecross, WA, Australia) were used in the first labora-
tory. The second laboratory applied cycle sequencing of
PCR products according to the protocol of Cereb & Yang
(1997), where exons 2 and 3 are amplified using primers
situated in introns 1 and 3 and detect a dimorphic
sequence motif. The sequencing primers are also situated in
the introns. Assignment of alleles was performed using
self-developed software comparing the sequence with
IMGT/HLA sequence database (Robinson et al., 2003).
When compared to the HLA-B*2702 sequence,
HLA-B*2730 has five nucleotide substitutions leading to
three amino acid exchanges. The nucleotide substitutions
are all located in the exon 3 at positions 283 (Χ→Τ), 285
(C→A), 292 (A→G), 293 (T→G) and 299 (T→C). Con-
sequently, all three amino acid exchanges are located in
the α 2 domain at positions 94 (Thr→Ile), 95 (Leu→Ile)
and 97 (Asn→Arg).
The mother of the patient was typed in the same manner
as the patient. While the patient appeared homozygous,
the mother’s phenotype was HLA-A*01, 03; B*08, 2730;
Cw*02, 07; DRB1*15, 16; DRB5. In her case, heterozygos-
ity for HLA-B alleles allowed separation before sequencing.
The two HLA-B alleles were separated with the primer pairs
B-TA/3BIn3–37 (GGC GGG GGC GCA GGA CCT GA/
AGG CCA TCC CCG SCG ACC TAT) that amplified the
B*08 and B-CG/3BIn3–37 (CGG GGG CGC AGG ACC
CGG/AGG CCA TCC CCG SCG ACC TAT). The HLA type
of the mother confirmed that the novel allele is part of the
haplotype HLA-A*03-B*2730-Cw*02-DRB1*16-DRB5
The nucleotide sequence data on B*2730 reported in this article have
been submitted to the EMBL nucleotide sequence database and were
assigned the accession number AJ969956. The name B*2730 was
officially assigned by the WHO Nomenclature Committee in June 2005.
This follows the agreed policy that, subject to the conditions stated in
the Nomenclature Report (Marsh et al., 2002), names will be assigned
to the new sequences, as they are identified. Lists of such new names
will be published in the following WHO Nomenclature Reports.
* Tissue Typing Centre, Blood Transfusion Centre of Slovenia, Ljubljana.
Slovenia, † Blood Group Serology, Medical University, Vienna, Austria,
‡ Department of Nephrology, University Clinical Centre, Ljubljana,
Slovenia
Received 22 May 2006; revised 05 July 2006; accepted 14 August 2006
Correspondence: Blanka Vidan-Jeras, Blood Transfusion Center of
Slovenia, Slajmerjeva 6, 1000 Ljubljana, Slovenia, Tel: 386 15438 224,
Fax: 386 14327 018, E-mail: blanka.vidan-jeras@ztm.si