Medical Research Society
6. HIDDEN GASTRIC AUTOANTIBODIES TO
INTRINSIC
FACTOR
IN
PERNICIOUS
ANAEMIA
RODNEY
BLUESTONE
and LEONARD
S. GOLDBERG
Departments of Medicine, Royal Postgraduate Medical
School, London, and University of California School of
Medicine, Los Angeles, California, U.S.A.
(Introduced by G. Neale)
Sera and gastric juices from twelve patients with
pernicious anaemia were examined for blocking and
binding autoantibodies to intrinsic factor (IF). The
concentrated gastric juices were subjected to Sephadex
G-100 gel filtration at pH 2.8 in order to dissociate
complexes of IF and antibody to IF, thereby allowing
the isolated components of the complexes to be
quantitated and characterized. Blocking antibodies
were present in six sera and both blocking and binding
antibodies were demonstrated in one serum. All serum
autoantibodies were of the IgG class of immunoglobulins. Blocking antibodies were detected in six
of the twelve concentrated whole gastric juices; one
of these also contained the binding antibody. In four
other specimens, blocking antibody was found only
after subjecting the concentrated gastric juices to
acidic gel filtration. The gastric antibodies were
predominantly IgG immunoglobulins except for one
which appeared to be a secretory IgA antibody.
Following fractionation of five gastric juices, the IF
content of the eluted peaks was greater than that of the
whole concentrated gastric juices.
These findings show that gastric juice of patients
with pernicious anaemia frequently contains autoantibodies to IF as well as IF. When the two exist as an
antigen-antibody complex neither component may be
detected unless the complex is first dissociated.
Further, the formation of such complexes depends in
part on gastric achlorhydria, a hallmark of pernicious
anaemia.
7. IMMUNOLOGICAL STUDIES I N HAEMOPHILIA
E. BENNETT
Department of Clinical Haematology, University
College Hospital Medical School, London
(Introduced by E. R. Huehns)
Haemophilia is a linked inherited bleeding disorder in
which there is lowered or absent factor VIII activity.
Recently it has been shown that this disease is a
protein disorder in which there are two groups of
patients: those who produce a factor VIII-like protein
which is functionally inactive, designated Haemophilia
A + ; and those in whom no protein can be detected,
designated Haemophilia A-. It has been shown by
immunological methods that the abnormal protein
cross reacts with antibodies formed against normal
factor VIII.
11P
In this communication an antibody to factor VIII
prepared in rabbits has been used to develop a quantitative assay for factor VIII like protein. This has been
used to investigate normal and haemophilic persons.
There is good correlation between the factor VIII
activity and the amount of protein detected in normal
individuals. In haemophiliacs the work confirms that
some patients carry a n abnormal, inactive protein,
whilst in others no protein can be detected. The
amount of this protein present varies from patient to
patient. One family has been investigated in more
detail. The two affected members both show similar
amount of protein with a low biological activity.
Study of two obligatory heterozygotes shows approximately twice the amount of protein by our immunological technique than biological activity. This quantitative technique may therefore allow the definitive
recognition of the female heterozygous state in some
families with this trait.
8. A SIMPLE METHOD O F MEASURING
TRANSMUCOSAL P.D. I N MAN AND ITS
CLINICAL APPLICATION
C. J. EDMONDS
and R. GODFREY
Medical Research Council, Department of Clinical
Research, University College Hospital Medical School,
London
The mucosal epithelium of the colon and rectum is
electrically polarized, in general the lumen being
negativelycharged with respect to the blood side of the
epithelium. Animal experiments have demonstrated
that the magnitude of the electrical potential difference
(p.d.) is affected by Na depletion and by aldosterone
administration (Edmonds & Marriott, 1967, Journal
of EndocrinoIogy, 39, 517-531) and is closely related
to the amount of sodium actively absorbed.
A simple technique has been devised allowing the
colonic p.d. in man to be measured rapidly at any
part of the bowel accessible to sigmoidoscopy.
Measurements on patients without bowel disease
showed little variation of p.d. to within 4 cm of the
anus, the majority of values being in the range 1 W
mV. Six hours after aldosterone administration (two
intravenous injections 0.5 mg at 2 hr interval), the p.d.
was generally in the range 45-70 mV. Study of the
time course of the changes after a single dose of aldosterone showed that the response developed in 4-6 hr
and had disappeared within 18 hr. Fludrocortisone
was also effective.
Using a modification of the method, the effects of
altering the composition of the solution in contact with
the mucosa have been examined. The results indicate
that the p.d. can be influenced by such changes.
Since rectal mucosa within a few centimetres of the
anus appears to respond to aldosterone, the present
technique offers the possibility of a simple method for
screening for aldosteronism.