The Tnpolyagglutinationhemolytic syndrome

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The Tn-polyagglutination/hemolytic syndrome - An
explanation after 50 year Stuart Kornfeld
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Case History 65 y/o man with no previous
disease developed acute infection in 1946 while
in Mexico. Episode complicated by severe anemia
requiring 5 transfusions. Also noted to have
leukopenia (2,900), thrombocytopenia (130,000),
and splenomegaly. Osmotic fragility test and
acid-serum test were normal. Between 1946
and 1952 anemia persisted. Retics increased at
8. RBC morphology showed increased ovalocytes
and tendency to auto agglutinate. There was no
panagglutination in the serum as seen in acquired
hemolytic anemia. Search for hemolysins was
negative. In 1952 an acute infection caused a
fall in RBC to 1.5 X 106 that required 6
transfusions. In 1955 patient tried on
prednisone (20-50 mg/day) with improvement in
anemia.
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• Workup of Polyagglutinability
• Patients RBCs (type B) were agglutinated by
  anti-A, anti-B and anti-AB sera from all donors
  as well as by his own serum.
• Sera from group A or O subjects, whose natural
  agglutinins were absorbed by corresponding red
  cells, still agglutinated patients RBCs.
• The agglutinin was termed anti-Tn.
• (3) The agglutinin in the patients serum
  seemed to be an immune anti-Tn since it did not
  have the same serologic characteristics as the
  natural anti-Tn that is present in natural adult
  serum.

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• To explain the combination of an acquired
  hemolytic anemia and polyagglutinability, two
  hypotheses were presented.
• The acquired hemolytic anemia had no relationship
  to the existence in the patient of a very rare
  group antigen, perhaps confined to the family
  (but RBCs of 25 family members did not react with
  the agglutinin).
• The hemolytic anemia is directly related to the
  existence of the Tn antigen on the patients red
  cells and is due to the development of an immune
  anti-Tn antibody against the Tn antigen, this
  last antigen being either a group antigen or an
  antigen revealed or modified by the causal agent
  of the disease.
• Hypothesis (b) turns out to be correct.

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Clinical Features of Tn-Syndrome Rare.
Occurrence estimated to be less than 1 in
150,000. Patients usually picked up when blood
sample exhibits polyagglutinability. Patients
generally do well except for minor signs of
hemolysis on thrombocytopenia. In Tn()
patients, the Coombs tests are usually negative
despite the fact that anti-Tn Igs are
ubiquitously present in serum.
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Clinical Findings in 18 Patients
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Berger E. G. (1999) Biochimica et Biophysica Acta
1455255-268
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The Tn expression occurs in hematopoietic stem
cells Platelets, leukocytes and RBC express
the Tn antigen.
Berger E. G. (1999) Biochimica et Biophysica Acta
1455255-268
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Structure of Tn Antigen
Berger E. G. (1999) Biochimica et Biophysica Acta
1455255-268
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Tn() cells lack Core I ? 1,3-Galactosyltransfera
se
T-cell clones
Berger E. G. (1999) Biochimica et Biophysica Acta
1455255-268
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Jurkat cells, a human T-leukemic cell line,
had been shown to be deficient in C1 Gal-T
activity and express truncated O-glycans bearing
the Tn-antigen. Authors found transcript for
C1 Gal-T to be highly expressed and to have a
normal sequence. Expression of a
recombinant epitope-tagged form of the enzyme did
not result in any detectable
protein. Conclude Some other factor may
post-transcriptionally regulate the expression of
the Gal-T protein and enzyme
activity. What is this factor? A CLUE came
from examining the protein sequence data obtained
with the purified rat liver enzyme. Two
N-terminal sequences were obtained in different
proportions. One matched the Gal-T, the other an
unknown protein.
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Gene located on X chromosome.
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Cancer (1997) 802240-2249
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Cancer Res (2008) 681636-1646
Find mutations in Cosmc cell lines from colon,
melanoma and cervical cancer patients.
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Conclusions The Tn-syndrome is caused by an
acquired mutation in the Cosmc gene located on
the X-chromosome. Cosmc functions as an
essential chaperone for the expression of Core 1
?1,3- Galactosyltrtansferase Mutations in
Cosmc are also found in several forms of cancer
and are associated with a poor prognosis.