UI  - 20057663
AU  - Santoso S
AU  - Amrhein J
AU  - Hofmann HA
AU  - Sachs UJ
AU  - Walka MM
AU  - Kroll H
AU  - Kiefel V
TI  - A point mutation Thr(799)Met on the alpha(2) integrin leads to the
      formation of new human platelet alloantigen Sit(a) and affects
      collagen-induced aggregation.
LA  - Eng
MH  - Animal
MH  - Antigens, CD/*genetics
MH  - Antigens, Human Platelet/*genetics
MH  - Blood Platelets/*physiology
MH  - Hamsters
MH  - Human
MH  - Methionine/genetics
MH  - Platelet Aggregation/*genetics
MH  - Point Mutation
MH  - Support, Non-U.S. Gov't
MH  - Threonine/genetics
RN  - 0 (integrin alpha2)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Human Platelet)
RN  - 7005-18-7 (Methionine)
RN  - 72-19-5 (Threonine)
PT  - JOURNAL ARTICLE
DA  - 20000110
DP  - 1999 Dec 15
IS  - 0006-4971
TA  - Blood
PG  - 4103-11
SB  - A
SB  - M
SB  - X
CY  - UNITED STATES
IP  - 12
VI  - 94
JC  - A8G
AA  - Author
EM  - 200003
AB  - A new platelet-specific alloantigen, termed Sit(a), was identified in a
      severe case of neonatal alloimmune thrombocytopenia. The Sit(a)
      alloantigen is of low frequency (1/400) in the German population.
      Immunochemical studies demonstrated that the Sit(a) epitopes reside on
      platelet glycoprotein (GP) Ia. Nucleotide sequence analysis of GPIa cDNA
      derived from Sit(a)-positive platelets showed C(2531)-->T(2531) point
      mutation, resulting in Thr(799)Met dimorphism. Analysis of genomic DNA
      from 22 Sit(a)-negative normal individuals showed that the Thr(799) is
      encoded by ACG(2532) (90.9%) or ACA(2532) (9.1%). To establish a DNA
      typing technique, we elucidated the organization of the GPIa gene adjacent
      to the polymorphic bases. The introns (421 bp and 1.2 kb) encompass a
      142-bp exon with the 2 polymorphic bases 2531 and 2532. Polymerase chain
      reaction-restriction fragment length polymorphism analysis on DNA derived
      from 100 donors using the restriction enzyme Mae III showed that the
      Met(799) form of GPIa is restricted to Sit(a) (+) phenotype. Analysis of
      stable Chinese hamster ovary transfectants expressing allele-specific
      recombinant forms of GPIa showed that anti-Sit(a) exclusively reacted with
      the Glu(505)Met(799), but not with the Glu(505)Thr(799) and the
      Lys(505)Thr(799) isoforms. In contrast, anti-Br(a) (HPA-5b) only
      recognized the Lys(505)Thr(799) form, whereas anti-Br(b) (HPA-5a) reacted
      with both Glu(505)Thr(799) and Glu(505)Met(799) isoforms. These results
      demonstrated that the Met(799) is responsible for formation of the Sit(a)
      alloantigenic determinants, whereas amino acid 505 (Lys or Glu)
      specifically controls the expression of Br(a) and Br(b) epitopes,
      respectively. Platelet aggregation responses of Sit(a) (+) individuals
      were diminished in response to collagen, indicating that the Thr(799)Met
      mutation affects the function of the GPIa/IIa complex.
AD  - Institute for Clinical Immunology, Justus Liebig University Giessen,
      Giessen, Germany. Santoso@immunologie.med.uni-giessen.de
PMID- 0010590055
URLF- http://www.bloodjournal.org/cgi/content/full/94/12/4103
URLS- http://www.bloodjournal.org/cgi/content/abstract/94/12/4103
EDAT- 1999/12/10 09:00
MHDA- 1999/12/10 09:00
SO  - Blood 1999 Dec 15;94(12):4103-11




