Gu ,
1991,32,29-35
Dissocia ion
be ween
sys emic
and
mucosal
humo al
immune
esponses
in
coeliac
disease
S
O'Mahony,
E
A anz,
J
R
Ba on,
A
Fe guson
Abs ac
We
examined
humo al
immuni y
in
coeliac
disease
as
exp essed
in
se um
(sys emic
immuni y),
and
in
sali a,
jejunal
aspi a e,
and
whole
gu
la age
luid
(mucosal
immuni y).
The
aims
we e
o
de ine
ea u es
o
he
sec e-
o y
immune
esponse
(IgA
and
IgM
con-
cen a ions
and
an ibody
alues
o
gliadin
and
o he
ood
p o eins
measu ed
by
enzyme
linked
immunoso ben
assay
(ELISA))
in
ac i e
disease
and
emission,
and
o
es ablish
whe he
sec e ions
ob ained
by
ela i ely
non-
in asi e
echniques
(sali a
and
gu
la age
luid)
can
be
used
o
indi ec
measu emen s
o
e en s
in
he
jejunum.
Se um,
sali a,
and
jejunal
aspi a e
om
26
adul s
wi h
un ea ed
coeliac
disease,
22
ea ed
pa ien s,
and
28
immunologically
no mal
con ol
subjec s
we e
s udied,
oge he
wi h
in es inal
sec e ions
ob ained
by
gu
la age
om
15
un ea ed
and
19
ea ed
pa ien s
wi h
coeliac
disease
and
25
con ol
subjec s.
Jejunal
aspi a e
IgA
and
IgM
and
gu
la age
luid
IgM
concen a ions
we e
signi ican ly
aised
in
pa ien s
wi h
un ea ed
coeliac
disease;
he
la age
luid
IgM
concen-
a ion
emained
highe
in
pa ien s
wi h
ea ed
coeliac
disease
han
in
con ols.
Se um
and
sali a y
immunoglobulin
concen a ions
we e
simila
in
he
h ee
g oups.
Pa ien s
wi h
un ea ed
coeliac
disease
had
highe
alues
o
an ibodies
o
gliadin
compa ed
wi h
ea ed
pa ien s
and
con ol
subjec s
in
all
body
luids
es ed;
hese
we e
p edominan ly
o
IgA
and
IgG
classes
in
se um,
and
o
IgA
and
IgM
classes
in
jejunal
aspi a e
and
gu
la age
luid.
Values
o
sali a y
IgA
an ibodies
o
gliadin
we e
signi ican ly
highe
in
un ea ed
coeliacs,
hough
an ibody
alues
we e
gene ally
low,
wi h
a
la ge
o e lap
be ween
coeliac
disease
pa ien s
and
con ol
subjec s.
In
ea ed
pa ien s,
wi h
p o ed
his ological
eco e y
on
glu en
ee
die ,
se um
IgA
an igliadin
an i-
body
alues
ell
o
con ol
alues,
hough
se um
IgG
an igliadin
an ibody
alues
emained
mode a ely
aised.
In
con as ,
he e
was
pe sis ence
o
sec e o y
an igliadin
an i-
bodies
in
ea ed
pa ien s
(pa icula ly
IgM
an ibody)
in
bo h
jejunal
aspi a e
and
gu
la age
luid.
An ibody
esponses
o
be alac o-
globulin
and
o albumin
we e
simila
o
hose
o
gliadin,
including
pe sis ence
o
high
in es-
inal
an ibody
alues
in
pa ien s
wi h
ea ed
coeliac
disease.
The e
was
a
posi i e
co ela-
ion
be ween
an ibody
alues
in
jejunal
aspi a e
and
gu
la age
luid,
bu
no
be ween
sali a
and
jejunal
aspi a e;
hus
sali a y
an i-
bodies
do
no
e lec
in es inal
humo al
immuni y.
Sys emic
humo al
immuni y
in
coeliac
disease
has
been
he
subjec
o
in ensi e
in es iga ion.
Nume ous
s udies
ha e
es ablished. ha
pa ien s
wi h
un ea ed
coeliac
disease
ha e
high
alues
o
ci cula ing
an ibodies
o
whea
de i ed
p o eins
such
as
gliadin,
and
ha
an ibody
alues
all
a e
a
pe iod
o
ea men
wi h
a
glu en
ee
die .''4
Es ima ion
o
se um
IgA
an igliadin
an ibody
is
now
ou inely
used
bo h
as
a
sc eening
es
o
coeliac
disease
and
as
a
means
o
assessing
die a y
compliance.
In
con as ,
in o ma ion
on
mucosal
immuni y
in
coeliac
disease
is
pa chy.
The e
ha e
been
many
s udies
o
mucosal
lymphoid
cells56
and
he e
is
ci cums an ial
e idence
o
a
local
cell
media ed
immune
esponse
o
glu en.78
Se e al
s udies
ha e
ca e ully
mapped
he
numbe s
o
Ig
p oducing
plasma
cells
in
he
jejunal
mucosa
o
pa ien s
wi h
un ea ed
and
ea ed
coeliac
disease,9
10
showing
ha
un ea ed
pa ien s
ha e
inc eased
numbe s
o
IgA
and
IgM
(and
o
a
lesse
ex en ,
IgG)
jejunal
plasma
cells.
In
he
1970s,
he
p esence
o
in es inal
an ibodies
o
ood
an igens
was
ecognised
by
a
ela i ely
insensi i e
p ecipi in
echnique,"
bu
he e
a e
only
wo
s udies
published,'2
1
bo h
in
child en,
on
he
iso ype
o
an ibodies
o
die a y
an igens
in
in es inal
sec e ions,
and
hese
gi e
con lic ing
esul s.
The
gene al
objec i es
o
his
s udy
we e
wo old.
In
ela ion
o
coeliac
disease,
ou
aim
was
o
cha ac e ise,
in
i o,
in es inal
humo al
immuni y.
To al
immunoglobulins
and
speci ic
an ibodies
o
gliadin
and
o
wo
an igens
which
a e
no
oxic
in
coeliacs
we e
measu ed
in
h ee
di e en
mucosal
sec e ions.
Un ea ed
and
ea ed
pa ien s
wi h
coeliac
disease
we e
s udied
o
de e mine
whe he
abno mali ies
o
sec e o y
immuni y
a e
pe manen
and
in insic
o
he
coeliac
dia hesis
o
a e
only
p esen
in
ac i e
disease.
Sepa a ely,
and
o
ele ance
o
he
clinical
in es iga ion
o
mucosal
immuni y,
we
s udied
he
ela ions
be ween
sys emic
and
in es-
inal
an ibodies,
and
we
examined
ou
da a
o
es ablish
whe he
pa e ns
o
immunoglobulins
and
an ibodies
in
jejunal
luid
a e
mi o ed
in
o he
sec e ions
which
can
be
ob ained
wi hou
in uba ion.
The
sali a y
glands
a e
conside ed
pa
o
he
common
mucosal
immune
sys em,'4
and
we
he e o e
s udied
pu e
pa o id
sali a.
We
also
used
a
whole
gu
la age
echnique
o
he
non-in asi e
collec ion
o
in es inal
sec e ions.
5
Me hods
PATIENTS
STUDIED
AT
THE
TIME
OF
JEJUNAL
BIOPSY
Specimens
o
sali a,
jejunal
aspi a e,
and
se um
we e
collec ed
a
he
same
ime
as
jejunal
biopsy
on
76
occasions
in
69
pa ien s.
The e
we e
41
pa ien s
wi h
coeliac
disease
(se en
s udied
wice),
(23
women
and
18
men;
median
age
42
yea s,
ange
15-78)
and
28
con ol
pa ien s
(14
Uni e si y
o
Edinbu gh
Gas oin es inal
Uni ,
Wes e n
Gene al
Hospi al,
Edinbu gh
S
O'Mahony
E
A anz
J
R
Ba on
A
Fe guson
Co espondence
o:
D
S
O'Mahony,
Gas oin es inal
Labo a o y,
Wes e n
Gene al
Hospi al,
C ewe
Road
Sou h,
Edinbu gh
EH4
2XU.
Accep ed
o
publica ion
5
Ma ch
1990
29
on Sep embe 1, 2020 a Uni e sidad de Valladolid. P o ec ed by copy igh .h p://gu .bmj.com/Gu : i s published as 10.1136/gu .32.1.29 on 1 Janua y 1991. Downloaded om
O'Mahony,
A anz,
Ba on,
Fe guson
women,
14
men,
median
age
35
yea s,
ange
14-75).
Con ol
subjec s
had
jejunal
biopsy
o
exclude
coeliac
disease
-
jejunal
his ology
in
hese
pa ien s
was
no mal,
no
o he
signi ican
pa hology
was
ound,
and
a
inal
diagnosis
o
unc ional
bowel
disease
was
made.
Twen y
six
o
he
pa ien s
wi h
coeliac
disease
we e
un-
ea ed
and
his ological
examina ion
o
he
jejunal
biopsy
specimens
showed
sub o al
o
se e e
pa ial
illous
a ophy.
Se en
o
hese
and
a
u he
15
pa ien s
wi h
ea ed
coeliac
disease
(all
wi h
p e ious
diagnos ic
biopsy
specimens)
unde wen
biopsy
again
while
on
a
glu en
ee
die .
The
median
pe iod
on
glu en
ee
die
was
h ee
yea s
( ange
3
mon hs
-
17
yea s).
Ele en
had
en i ely
no mal
jejunal
his ology
(all
o
hese
had
been
aking
a
glu en
ee
die
o
a
leas
wo
yea s),
and
11
had
mino
his ological
changes
-
o
example
inc eased
in aepi helial
lympho-
cy es
(mos
pa ien s
in
his
g oup
had
been
aking
a
glu en
ee
die
o
less
han
one
yea ).
PATIENTS
STUDIED
BY
WHOLE
GUT
LAVAGE
Gu
la age
was
ca ied
ou
in
15
un ea ed
coeliac
disease
pa ien s,
19
wi h
ea ed
disease,
and
25
con ol
pa ien s.
These
included
10,
eigh ,
and
wo
pa ien s
espec i ely
om
each
g oup
who
had
also
had
collec ion
o
jejunal
aspi a e.
The
median
pe iod
on
a
glu en
ee
die
in
pa ien s
wi h
ea ed
coeliac
disease
unde going
gu
la age
was
eigh
yea s
( ange
3
mon hs
-
19
yea s).
Ele en
o
he
pa ien s
on
a
glu en
ee
die
had
in
he
pas
shown
a
clinical
and
his ological
esponse
o
he
die ,
bu
did
no
unde go
biopsy
again
a
he
ime
o
his
s udy.
Gu
la age
was
ca ied
ou
in
25
con ol
pa ien s
(16
women
and
nine
men,
median
age
52,
ange
21
-
92
yea s).
These
subjec s
we e
ei he
heal hy
olun ee s
o
pa ien s
wi h
unc ional
bowel
diso de .
SPECIMEN
COLLECTION
AND
PROCESSING
Sali a:
pa o id
sali a y
low
was
s imula ed
wi h
5%
ci ic
acid
sublingually
in
ou
0
5
ml
aliquo s
o e
i e
minu es,
and
collec ed
ia
a
Ca lsson-
C i enden
cup
placed
o e
he
pa o id
duc ,
wi h
gen le
aspi a ion
o
main ain
posi ion
and
suc ion.
We
collec ed
s imula ed
sali a
only.
Jejunal
aspi a e:
samples
we e
collec ed
om
a
poin
jus
dis al
o
he
duodenal-jejunal
junc ion,
h ough
he
ubing
o
he
C osby
capsule,
be o e
aking
he
biopsy
specimen.
The
p o ease
inhibi o
phenylme hyl
sulphonyl luo ide
(PMSF,
Sigma)
100
mM
in
95%
alcohol
(20
,ul
pe
ml
o
aspi a e)
was
added
be o e
aliquo ing.16
Se um
was
ob ained
om
all
pa ien s.
Gu
la age:
he
la age
luid
used
was
a
poly-
e hylene
glycol
(PEG)
based
elec oly e
la age
solu ion
(Goly ely).
A e
an
o e nigh
as ,
pa ien s
d ank
his
solu ion
a
a
a e
o
250
ml
e e y
15
minu es
o
a
pe iod
o
ou
hou s,
making
he
o al
olume
consumed
ou
li es.
Specimen
collec ion
began
once
he
ma e ial
passed
pe
ec um
became
liquid,
clea ,
and
ee
o
aecal
ma e ial.
App oxima ely
200
ml
was
collec ed
and
il e ed
in o
50
ml
polyp opylene
ubes;
specimens
we e
cen i uged
and
ea ed
wi h
p o ease
inhibi o s
as
desc ibed
by
Gaspa i
e
al.'5
All
he
abo e
specimens
we e
aliquo ed
and
s o ed
a
-70°C.
ENZYME
LINKED
IMMUNOSORBENT
ASSAY
(ELISA)
Re e ence
ma e ials
and
epo ing
o
esul s
Fo
assays
o
immunoglobulins
in
he
a ious
sec e ions,
se ial
wo old
dilu ions
o
a
s anda d
p epa a ion
we e
used
o
p oduce
a
s anda d
cu e.
Fo
example,
o
IgA
assays
dilu ions
anging
om
1250-19-35
ng/ml
o
a
human
colos al
IgA
s anda d
(Sigma)
we e
used
in
each
es
un.
Se ial
dilu ions
o
es
samples
( a ying
in
ini ial
dilu ion
depending
on
he
ype
o
specimen)
we e
also
assayed.
Only
when
he
op ical
densi y
esul s
o
a
leas
wo
o
hese
sample
dilu ions
ell
wi hin
he
ange
o
he
s anda d
cu e
was
he
assay
conside ed
echni-
cally
sa is ac o y.
The
IgA
con en
o
he
sample
was
hen
de e mined
by
aking
he
mean
IgA
con en
o
hese
wo
sample
dilu ions.
Fo
o al
IgM
and
IgG
in
sec e ions
human
e e ence
se um
(P o ein
Re e ence
Uni ,
She ield)
was
used
as
a
s anda d.
In
he
assays
o
speci ic
an ibodies,
expe i-
men s
we e
ca ied
ou
o
de ine
op imal
es
condi ions
o
each
an igen,
iso ype,
and
sec e-
ion.
Se um
om
a
pa ien
wi h
un ea ed
coeliac
disease,
p e iously
ecognised
as
ha ing
high
i es
o
an ibodies
o
all
iso ypes
o
a
wide
a ie y
o
die a y
an igens,
was
used
as
a
e e ence
s anda d.
The
e e ence
specimen
and
es
specimens
we e
s udied
a
sui able
dilu ions,
a ying
o
he
di e en
assays,
and
he
pla es
we e
ead
when
he
op ical
densi y
o
he
s anda d
eached
1-0.
Resul s
o
es
specimens
a e
exp essed
as
op ical
densi y
eadings,
%
o
his
s anda d.
Resul s
a e
hus
exp essed
as
non-
pa ame ic
da a;
an ibody
alues
a e
no
di ec ly
p opo ional
o
he
an igen
binding
capaci y
o
he
sample.
This
is
a
ea u e
o
all
such
assays.
Immunoglobulins
(jejunal
aspi a e,
gu
la age
luid,
and
sali a)
Assays
we e
pe o med
in
96
well
mic o i e
ELISA
pla es
(Dyna ech).
All
eac an s
we e
added
in
olumes
o
0-125
ml
pe
well
and
all
washes
we e
done
h ee
imes
using
saline
wi h
0
05%
Tween-80
added.
Fo
he
assay
o
o al
IgA,
wells
we e
coa ed
wi h
100
ng/ml
a ini y
pu i ied
goa
an ihuman
IgA
(No heas
Labs)
in
0-1
M
ca bona e
bu e ,
pH
9
6,
and
incuba ed
o e nigh
a
4°C
and
washed.
A e
washing,
se ial
wo old
dilu ions
o
s anda d
and
samples
(ini ial
sample
dilu ion
1/100)
we e
added
o
he
coa ed
wells.
Pla es
we e
incuba ed
o e nigh
a
4°C
and
washed.
Goa
an ihuman
IgA
con-
juga ed
wi h
alkaline
phospha ase
(No heas
Labs)
dilu ed
(in
saline
wi h
1%
e al
cal
se um
and
0
05%
Tween-80)
o
a
p ede e mined
op imal
alue
was
added
and
pla es
we e
in-
cuba ed
o
h ee
hou s
a
20°C.
A e
washing,
pa ani ophenylphospha e
(PNPP,
Sigma)
1
mg/ml
in
10%
die hanolamine
(DEA)
bu e ,
pH
9-8,
was
added.
Pla es
we e
ead
a
op ical
densi y
405
in
an
MR580
mic oELISA
eade
(Dyna ech).
The
IgA
con en
o
any
gi en
sample
was
de e mined
as
desc ibed
abo e.
30
on Sep embe 1, 2020 a Uni e sidad de Valladolid. P o ec ed by copy igh .h p://gu .bmj.com/Gu : i s published as 10.1136/gu .32.1.29 on 1 Janua y 1991. Downloaded om
Dissocia ion
be ween
sys emic
and
mucosal
humo al
immune
esponses
in
coeliac
disease
The
me hod
used
o
de e mine
o al
IgM
and
IgG
in
sec e ions
was
simila ;
ini ial
sample
dilu ion
was
1/25.
Se um
immunoglobulins
we e
measu ed
by
au oanalyse
using
an
immuno u bidime ic
me hod.
Food
an ibodies
The
assay
was
simila
o
ha
desc ibed
abo e.
Immulon
2
(129B)
ELISA
pla es
(Dyna ech)
we e
used.
Wells
we e
coa ed
wi h
an igen
(gliadin,
be alac oglobulin
and
o albumin)
a
a
concen a ion
o
5
, g/ml.
Be alac oglobulin
and
o albumin
we e
supplied
by
Sigma;
gliadin
was
supplied
by
D
S e an
S obel.
Re e ence
s an-
da d
and
samples
we e
added
in
duplica e
dilu-
ions
o
he
coa ed
wells.
The
ollowing
sample
dilu ions
we e
used:
se um:
1/100
(IgA
and
IgM)
and
1/200
(IgG);
jejunal
aspi a e:
1/10;
gu
la age
luid:
1/2;
sali a:
1/2.
An
app op ia e
dilu ion
o
s anda d
was
included
in
each
assay;
hese
dilu ions
ga e
op imal
op ical
densi y
eadings.
We
es ablished
ha
hese
an ibodies
we e
speci ic
by
incuba ing
samples
wi h
he
ele an
TABLE
I
Immunoglobulin
concen a ions
(median
( ange))
in
se um
(mglml),
jejunal
aspi a e,
gu
la age
luid,
and
sali a
(Isg/ml)
Ig
Un ea ed
T ea ed
Con ol
class
coeliac
pa ien s
coeliac
pa ien s
subjec s
Se um
IgA
2-4(1-3-3-8)
2-0(0
7-3
3)
1-8(0-9-4-1)
IgM
1
1(03-34)
09(0-3-3-1)
1-3(03-4-5)
IgG
10-5
(5-6-15-7)
10-7
(5-4-20-1)
9-5
(7-3-15-9)
Jejunal
aspi a e
IgA
290*
(25-2282)
140-7
(20-1558)
102-5
(22
9-540
6)
IgM
29.8*
(1
9-357
9)
9-6
(0-174-4)
4.5
(0-39
5)
IgG
23-9*
(3-261-8)
11-8
(0-3-271-4)
7-3
(1-2-29-3)
Gu
la age
luid
IgA
146-2
(10-7-487-5)
90-8
(8-8-621-8)
139-7
(7
9-403)
IgM
17-5*
(2-1-100-1)
25.7*
(0-192-2)
5
3
(0-37)
IgG
2-7
(0-1-34-9)
0-9
(0-1-11-4)
1-0
(0-12-2)
Sali a
IgA
123-8(48
6-454)
118-1
(32-2-838-2)
165-8
(66-5-606
9)
IgM
1-2(0-1-138-9)
1-4(0-1-12-4)
1
1(0-1-3-6)
IgG
1-3
(0-25-1)
0-9
(0-1-10-6)
0.5
(0-34-3)
*Immunoglobulin
concen a ion
signi ican ly
highe
(p<005)
han
in
con ol
subjec s.
Immunoglobulin
concen a ion
signi ican ly
highe
(p<005)
han
in
ea ed
coeliac
disease
pa ien s.
TABLE
II
Se um
ood
an ibody alues
(median
( ange))
Un ea ed
T ea ed
Con ol
Ig
coeliac
pa ien s
coeliac
pa ien s
subjec s
An igen
class
(n=26) (n=22)
(n=28)
Gliadin
IgA
43-7* (4-6-150)
5-8(0-3-41-9)
5
3(0-44-5)
IgM
43
0(19-3-95-4)
38-6
(10-5-87-6)
47-9(16-1-108-8)
IgG
82-4*
(9-8-137-4)
41-6*
(6-8-107-4)
21
(0-105-2)
BLG
IgA
14.7* (1I
4-150)
6-6*(2-1-87-5)
3-3(0
2-36
4)
IgM
33-6(9-125-5)
38-7(11-3-94-6)
27-4
(3
5-82
2)
IgG
94.7*
(5-150)
70-2
(8-6-150)
30
9
(0-131-8)
OVA
IgA
18-8*
(2-6-150)
14-8
(4
8-606)
11-4
(0
9-35-9)
IgM
31-1(4-87)
37-8
(9-5-123-4)
30-0
(5-7-102-6)
IgG
64-4
(2-6-150)
63-4*
(8-4-150)
27-6
(3-6-150)
*An ibody
alues
signi ican ly
highe
(p<005)
han
in
con ol
subjec s.
An ibody
alues
signi ican ly
highe
(p<005)
han
in
ea ed
coeliac
disease
pa ien s.
BLG=be alac oglobulin;
OVA=o albumin.
TABLE
III
Jejunal
aspi a e
an ibody
Un ea ed
T ea ed
Con ol
Ig
coeliac
pa ien s
coeliac
pa ien s
subjec s
An igen
class
(n=26)
(n=22)
(n=28)
Gliadin
IgA
265*
(0-7-134-5)
4.0*(03-342)
1-1(0-13-3)
IgM
80
5*
(0-1-150)
19-6*
(2-1-114-4)
1-9(0-11-7)
IgG
1-8*
(0-23
4)
1-0*
(0-4
8)
0-2
(0-2
2)
BLG
IgA
25.3*
(0-6-150)
9-2(1
1-110
9)
50
(0-1-60-8)
IgM
16-4*
(0-150)
9-2*
(1
-1-78-
3)
1-6(0-11-7)
IgG
4.5*(0-104)
1-6(0-35-1)
1-0(0-7-7)
OVA
IgA
15-8*
(4-150)
19-6*
(1-5-6-5)
4-2
(0-100-5)
IgM
18-7*
(0-97)
8-4*
(0-
1-52.5)
1*1(0-17-7)
IgG
1-3*
(0-26.2)
1
1(0-11-7)
0
5
(0-26
5)
*An ibody
alues
signi ican ly
highe
(p<005)
han
in
con ol
subjec s.
An ibody
alues
signi ican ly
highe
(p<0-05)
han
in
ea ed
coeliac
disease
pa ien s.
BLG=be alac oglobulin;
OVA=o albumin.
an igen
and
showing
ha
he
an ibody
was
speci ically
abso bed
ou .
In
a
s udy
o
20
samples,
he
wi hin
pla e
op ical
densi y
coe i-
cien
o
a ia ion
was
7-3%,
and
he
be ween
pla e
op ical
densi y
a ia ion
was
11-1%.
I
he
op ical
densi ies
o
he
duplica e
sample
dilu-
ions
a ied
by
>
15%,
he
assay
was
epea ed.
STATISTICAL
METHODS
Di e ences
in
an ibody
alues
and
immuno-
globulin
con en
we e
analysed
using
he
Mann-
Whi ney
U
es .
Fo
co ela ions,
Spea man's
es
was
used.
Resul s
IMMUNOGLOBULIN
CONCENTRATIONS
(TABLE
I)
Se um
No
signi ican
di e ences
we e
obse ed.
Jejunal
aspi a e
Un ea ed
coeliac
disease
pa ien s
had
signi i-
can ly
highe
jejunal
aspi a e
concen a ions
o
IgA,
IgM,
and
IgG
compa ed
wi h
con ols,
and
highe
IgM
compa ed
wi h
pa ien s
wi h
ea ed
coeliac
disease.
Values
o
ea ed
coeliac
disease
pa ien s
we e
no
signi ican ly
di e en
om
hose
o
con ol
subjec s.
Gu
la age
luid
IgM
con en
was
signi ican ly
highe
in
bo h
un ea ed
and
ea ed
coeliac
disease
pa ien s
han
in
con ol
subjec s
.
Sali a
No
signi ican
di e ences
we e
obse ed.
ANTIBODIES
TO
FOOD
PROTEINS
Se um
(Table
II)
Un ea ed
coeliac
disease
pa ien s
had
high
alues
o
se um
IgA
an igliadin
an ibody,
wi h
alues
o
ea ed
coeliac
disease
pa ien s
simila
o
con ol
alues.
High
alues
o
se um
IgG
an igliadin
an ibody
we e
ound
in
bo h
un-
ea ed
and
ea ed
coeliac
disease
pa ien s,
wi h
signi ican ly
highe
alues
in
he
un ea ed
pa ien s.
The e
we e
no
signi ican
di e ences
be ween
pa ien
g oups
in
alues
o
se um
IgM
an ibodies.
Pa e ns
o
se um
an ibodies
o
OVA
and
be alac oglobulin
we e
gene ally
simila
o
hose
o
an igliadin
an ibody,
as
de ailed,
wi h
s a is ical
in o ma ion
in
Table
II.
Un ea ed
pa ien s
had
high
alues
o
IgA
and
IgG
an i-
be alac oglobulin
an ibody
and
IgA
an i-
o albumin
an ibody.
Se um
IgA
an i-be alac o-
globulin
and
IgG
an io albumin
an ibody
alues
we e
highe
in
ea ed
pa ien s
han
in
con ol
subjec s.
Jejunal
aspi a e
(Table
III)
The e
was
e y
li le
an ibody
de ec ed
in
jejunal
31
on Sep embe 1, 2020 a Uni e sidad de Valladolid. P o ec ed by copy igh .h p://gu .bmj.com/Gu : i s published as 10.1136/gu .32.1.29 on 1 Janua y 1991. Downloaded om
O'Mahony,
A anz,
Ba on,
Fe guson
Figu e
1:JIejunal
aspi a e
IgA
and
IgM
an igliadin
an ibody
alues.
(Median
an ibody
alues
shown
as
ho izon al
ba s.)
160
-
140
120
2
100
-
80
s
60
c}
a
-3
60-
z
0
40
20
-
0
IgA
p<
0.00001
I
p<
0-0002
'
p<
0-002
*
*
^
UCD
TCD
C
IgM
p
<
0.00001
p<
0-005
'
p<
0-00001
.
-4-
I
BP
4-
-WY,-
1
_ _
_~~-1
UCD
TCD
C
T ea ed
coeliac
pa ien s
wi h
mino
jejunal
his ological
changes
T ea ed
coeliac
pa ien
wi h
en i ely
no mal
jejunal
his ology
I
160
.
140
-
120
-
2
100-
Z
!
80-
60
0
40!
20
IgA
p<0-002
p
<
0-02
p
<005
-I-
OL
_
IgM
p
<
0-0002
p<
0.05
p
<
0-005
sol
- -
IS!1
0*~-
UCD
TCD
C
UCD
TCD
C
Figu e
2:
Gu
la age luid
IgA
and
IgM
an igliadin
an ibody
alues.
(Median
an ibody
le els
shown
as
ho izon al
ba s.)
aspi a es
om
con ol
subjec s,
bu
as
de ailed
in
Table
III,
o
all
h ee
iso ypes
and
all
h ee
an igens
s udied,
an ibody
alues
we e
signi i-
can ly
highe
in
jejunal
aspi a es
om
un ea ed
pa ien s
han
om
con ol
subjec s
(p
alues
all
<002).
Fo
an igliadin
an ibodies,
alues
in
ea ed
coeliac
pa ien s
we e
in e media e
be ween
un ea ed
coeliac
disease
pa ien s
and
con ol
subjec s
and
signi ican ly
di e en
om
bo h.
When
an ibody
alues
in
he
11
ea ed
pa ien s
wi h
en i ely
no mal
jejunal
his ology
we e
compa ed
wi h
hose
in
con ol
subjec s,
IgA
an igliadin
an ibody
alues
we e
no
signi i-
can ly
highe .
Con e sely,
IgM
an igliadin
an i-
body
alues
emained
signi ican ly
aised
(p<O0OO5)
in
his
g oup.
An ibodies
o
be alac o-
globulin
and
o albumin
showed
a
g ea e
o e -
TABLE
IV
Gu
la age luid
an ibody
alues
Un ea ed
T ea ed
Con ol
Ig
coeliac
pa ien s
coeliac
pa ien s
subjec s
An igen
class
(n
=
15)
(n=19)
(n=25)
Gliadin
IgA
53-6*
(2-2-137-8)
9-2*
(0
4-72
9)
2-2
(0-57
9)
IgM
569*
(8-150)
17-9*
(0-2-150)
3-1
(0-88-7)
IgG
0.4*
(0-2-19)
0-6
(0-3)
0-2
(0-6-5)
BLG
IgA
7
9*(1-8-85-5)
8-4(0&6-76
5)
3-5(0-1-71-2)
IgM
5-6*(0-14-5)
5.3*(0-53)
0-1(0-22-6)
IgG
07(0-21)
04(0-8-1)
04(0-44)
OVA
IgA
15-0*
(3
7-39
3)
14-7*
(0
5-46
8)
4-8
(0-76)
IgM
6-6*(0
8-33
3)
3-6*(0-46
3)
0
9(0-20
6)
IgG
0
3*
(0-1-3)
0-0
(0-61-2)
0
0
(0-3
6)
*An ibody
alues
signi ican ly
highe
(p<0
05)
han
in
con ol
subjec s.
An ibody
alues
signi ican ly
highe
(p<005)
han
in
ea ed
coeliac
disease
pa ien s.
TABLE
V
Sali a y
an ibody
alues
Un ea ed
T ea ed
Con ol
Ig
coeliac
pa ien s
coeliac
pa ien s
subjec s
An igen
class
(n=26)
(n=22)
(n=28)
Gliadin
IgA
5
1* (0-1-29-6)
4-2(0-12-5)
30(0-11-7)
IgM
5-1(0-150)
5
4(0-35-9)
2-4(0-15-5)
IgG
0.3*
(0-17-9)
0-0
(0-4
6)
0-0
(0-7
6)
BLG
IgA
8-3*
(I-9-53-7)
8-3*
(0-46.5)
5-3
(0-29
8)
IgM
1-0(0-28
3)
1-2(0-14-4)
0-8(0-11-9)
IgG
0-4(0-58)
0
0(0-18-8)
0
0(0-2
9)
OVA
IgA
15-8
(1-9-92-9)
13-2
(06-34)
14-3
(34-30
2)
IgM
1-2(0-34
1)
1-4(0-16-7)
1-3(0-13-3)
IgG
00(0-13)
0-0(0-3-1)
0-0(0-1-7)
*An ibody
alues
signi ican ly
highe
(p<005)
han
in
con ol
subjec s.
An ibody
alues
signi ican ly
highe
(p<005)
han
in
ea ed
coeliac
disease
pa ien s.
BLG=
be alac oglobulin;
OVA=o albumin.
lap
be ween
alues
in
coeliac
disease
pa ien s
and
con ol
subjec s,
bu
again
high
IgM
an ibody
alues
pe sis ed
in
he
ea ed
pa ien s.
Jejunal
aspi a e
IgA
and
IgM
an igliadin
an ibody
alues
a e
shown
in
Figu e
1.
Gu
la age
luid
(Table
IV)
As
in
jejunal
aspi a e,
high
alues
o
IgA
and
IgM
an ibodies
o
gliadin
we e
ound
in
bo h
un ea ed
and
ea ed
coeliac
disease
pa ien s
compa ed
wi h
con ol
subjec s,
wi h
signi i-
can ly
highe
an ibody
alues
in
he
un ea ed
compa ed
wi h
he
ea ed
pa ien s.
High
alues
o
IgA
and
IgM
an ibodies
o
be alac oglobulin
and
o albumin
we e
ound
in
un ea ed
pa ien s;
high
alues
o
IgA
and
IgM
an i-o albumin
and
IgM
an i-be alac oglobulin
an ibodies
pe sis ed
in
he
ea ed
coeliac
disease
pa ien s.
Gu
la age
luid
IgA
and
IgM
an igliadin
an ibody
alues
a e
shown
in
Figu e
2.
Sali a
(Table
V)
Sali a y
an ibody
alues
we e
gene ally
low,
wi h
la ge
o e laps
beween
pa ien
g oups.
Un-
ea ed
coeliac
disease
pa ien s
had
highe
alues
o
IgA
and
IgG
an igliadin
an ibodies
compa ed
wi h
con ol
subjec s;
only
IgA
an igliadin
an i-
body
alues
we e
highe
han
in
he
ea ed
pa ien s.
Highe
alues
o
IgA
an i-be alac o-
globin
an ibody
we e
ound
in
bo h
un ea ed
and
ea ed
coeliac
disease
pa ien s
compa ed
wi h
con ol
subjec s.
SERIAL
STUDIES
IN
COELIAC
DISEASE
PATIENTS
Se en
coeliac
disease
pa ien s
who
had
a
clinical
and
his ological
esponse
o
a
glu en
ee
die
we e
s udied
be o e
and
a e
ea men .
Se ial
changes
in
se um
IgA
an igliadin
an ibody
and
jejunal
aspi a e
IgA
and
IgM
an igliadin
an i-
bodies
a e
shown
in
Figu e
3.
Whe eas
se um
an ibody
alues
ell
signi ican ly
(p<0
05)
wi h
ea men ,
he e
was
no
signi ican
change
in
he
alues
o
in es inal
an ibody
despi e
his ological
I
I
s
32
A
o
on Sep embe 1, 2020 a Uni e sidad de Valladolid. P o ec ed by copy igh .h p://gu .bmj.com/Gu : i s published as 10.1136/gu .32.1.29 on 1 Janua y 1991. Downloaded om
Dissocia ion
be ween
sys emic
and
mucosal
humo al
immune
esponses
in
coeliac
disease
Figu e
3:
Se ial
changes
in
alues
o
se um
an igliadin
an ibody
and
jejunal
aspi a e
IgA
and
IgM
an igliadin
an ibodies
in
7
coeliac
disease
pa ien s
be o e
and
a e
ea men
wi h
glu en
ee
die .
ND=no mal
die ;
GFD=glu en
ee
die .
Se um
IgA
an i
-gliadin
1-5
-o
m
-n
10
0
-0
Q
05
0-
-o
0
15-
1*0-
0-5-
Aspi a e
IgA
an i
-gliadin
1
5-
1
0-
0-5-
0
Aspi a e
IgM
an i
-gliadin
ND
GFD
eco e y
on
a
glu en
ee
die .
The e
was,
in
ac ,
a
end
owa ds
highe
alues
o
IgM
an ibody
a e
ea men .
I
should
be
no ed
ha
hese
se en
pa ien s
had
been
aking
a
glu en
ee
die
o
six
mon hs
o
less,
which
may
accoun
o
he
ac
ha
hey
beha ed
di e en ly
om
he
ea ed
coeliac
disease
pa ien s
as
a
whole,
who
had
signi ican ly
lowe
jejunal
aspi a e
an ibody
alues
compa ed
wi h
un ea ed
coeliac
disease
pa ien s.
CORRELATIONS
BETWEEN
ANTIBODY
VALUES
IN
JEJUNAL
ASPIRATE,
GUT
LAVAGE
FLUID,
SERUM,
AND
SALIVA
(TABLE
VI)
IgA
an igliadin
an ibody
alues
we e
compa ed
in
he
a ious
body
luids
es ed.
In
he
un ea ed
coeliac
disease
pa ien s,
we
ound
a
posi i e
co ela ion
be ween
an ibody
alues
in
se um
and
jejunal
aspi a e
( =0-68,
p<0-0001)
bu
in
he
ea ed
coeliac
disease
pa ien s
his
co ela-
ion
was
no
main ained
as
hey
had
high
alues
o
jejunal
aspi a e
an ibody,
whe eas
se um
an ibody
alues
we e
low
o
absen .
In
he
con ol
g oup,
he e
was
a
posi i e
co ela ion
( =0-59,
p<0-001)
be ween
an ibody
alues
in
se um
and
sali a.
No
co ela ion
was
ound
be ween
sali a y
and
jejunal
aspi a e
an ibody
alues
in
any
o
he
h ee
g oups.
Bo h
jejunal
aspi a e
and
gu
la age
luid
had
been
collec ed
om
20
pa ien s
( om
all
h ee
pa ien
g oups).
A
posi i e
co ela ion
( =079,
p<00l)
was
ound
be ween
an ibody
alues
in
jejunal
aspi a e
and
gu
la age
luid.
Discussion
In es inal
an igliadin
an ibodies
in
coeliac
disease
pa ien s
we e
mainly
in
he
IgA
and
IgM
classes,
and
signi ican
amoun s
o
IgM
an ibody
pe sis ed
in
he
sec e ions
o
ea ed
coeliac
disease
pa ien s
wi h
en i ely
no mal
jejunal
his ology.
Sec e ed
IgA
an ibody
was
de ec ed
bnly
in
he
subg oup
o
ea ed
coeliac
disease
pa ien s
wi h
mino
his ological
abno mali ies,
mos
o
whom
had
had
less
han
a
yea 's
ea -
men
wi h
a
glu en
ee
die .
I
is
possible
ha
he
in es inal
IgA
an igliadin
an ibody
and
mino
his ological
changes
could
bo h
be
due
o
con-
inued
inges ion
o
small
amoun s
o
glu en.
Con e sely,
in es inal
IgM
an ibody
alues
emained
highe
han
in
con ol
subjec s,
e en
in
pa ien s
wi h
comple ely
no mal
jejunal
mucosa
who
had
been
aking
a
glu en
ee
die
o
some
yea s.
I
is
likely
ha
minu e
amoun s
o
glu en
(comple e
compliance
o
a
glu en
ee
die
is
di icul
o
achie e
in
adul s)
main ains
a
local
immune
esponse
a he
han
a
sys emic
one.
Ou
inding
o
a
pe sis en
IgM
an ibody
es-
ponse
pa allels
he
inding
o
a
ela i ely
high
ac ion
o
IgM
plasma
cells
in
ea ed
coeliac
disease
pa ien s.9
We
ound
high
alues
o
se um
IgA
and
IgG
an igliadin
an ibody
in
un ea ed
coeliac
disease
pa ien s.
In
he
ea ed
pa ien s,
se um
IgA
an igliadin
an ibody
alues
we e
simila
o
hose
in
con ols
bu
se um
IgG
an igliadin
an ibody
alues,
hough
signi ican ly
lowe
han
in
he
un ea ed
coeliac
disease
pa ien s,
emained
signi ican ly
highe
han
in
con ol
subjec s.
These
indings
ag ee
wi h
hose
o
o he
epo s.'7
18
Concen a ions
o
IgA,
IgM,
and
IgG
we e
all
high
in
jejunal
aspi a es
om
un ea ed
coeliac
disease
pa ien s.
Coun s
o
jejunal
plasma
cells
and
in
i o
immunoglobulin
p oduc ion
in
coeliac
disease
a e
highe
han
in
con ol
subjec s
o
all
iso ypes,'0
suppo ing
he
iew
ha
he
immunoglobulins
(a
leas
IgA
and
IgM)
in
coeliac
in es inal
sec e ions
a e
p oduced
locally.
TABLE
VI
Co ela ion
be ween
IgA
an igliadin
an ibody
alues
in
se um,
jejunal
aspi a e,
and
sali a
Se um
and
Se um
and
Sali a
and
G oup
sali a
aspi a e aspi a e
Un ea ed
coeliac
disease
=0
021
=0-68
=0-293
(n=26)
(NS)
(p<0-0001)
(NS)
T ea ed
coeliac
disease
=0-392
=0-04
=0-323
(n=22)
(NS) (NS)
(NS)
Con olsubjec s
-0
593
=
-0
193
=0-071
(n=28)
(p<0
001)
(NS)
(NS)
NS
=no
signi ican .
33
on Sep embe 1, 2020 a Uni e sidad de Valladolid. P o ec ed by copy igh .h p://gu .bmj.com/Gu : i s published as 10.1136/gu .32.1.29 on 1 Janua y 1991. Downloaded om

34
O'Mahony,
A anz,
Ba on,
Fe guson
I
is
likely
ha
mos
o
he
jejunal
IgG
is
plasma
de i ed
as
he
numbe s
o
IgG
sec e ing
plasma
cells
a e
low
e en
in
un ea ed
coeliac
disease.'
We
should
poin
ou
ha
immunoglobulin
measu ed
in
jejunal
aspi a e
was
o al
immuno-
globulin
and
no
speci ic
sec e o y
IgA
and
IgM.
I
is
possible
ha
a
leas
some
o
he
jejunal
IgA
and
IgM
is
se um
de i ed
(coeliac
disease
is
a
p o ein
losing
diso de ).
We
a e
cu en ly
cha ac e ising
jejunal
immunoglobulins
and
an ibody
in
e ms
o
molecula
weigh
and
pe cen age
o
o al
Ig
which
con ains
a
sec e o y
componen .
An
inc ease
in
he
in es inal
luid
immunoglobulin
con en
was
no
accompanied
by
equi alen
changes
in
se um
immuno-
globulins;
in
ac ,
he
se um
IgM
con en
was
no iceably
low
in
some
un ea ed
coeliac
disease
pa ien s.
We
ha e
no
ye
assessed
he
con ibu ion
o
speci ic
an igliadin
an ibody
o
he
inc ease
in
in es inal
immunoglobulin
con en
in
coeliac
disease.
Falchuk
and
S obe ,'9
using
an
a ini y
ch oma og aphy
echnique,
epo ed
ha
app oxima ely
hal
o
he
ne
inc ease
in
IgA
and
IgM
syn hesis
(in
an
in
i o
model
o
glu en
challenge)
was
due
o
syn hesis
o
an igliadin
an ibody.
Con e sely,
in
a
mo e
ecen
epo
o
in
i o
sec e ion
o
an igliadin
an ibody
by
coeliac
jejunal
mucosal
biopsy
specimens,20
Cicli e a
e
al
calcula ed
ha
an igliadin
an ibody
accoun ed
o
2
1%,
12-
1%,
and
4
1%
o
he
o al
concen a ions
o
IgA,
IgM,
and
IgG
espec i ely.
In
any
e en ,
enhanced
in es inal
an ibody
p oduc ion
in
coeliac
disease
is
no
limi ed
o
glu en
de i ed
p o eins:
we
ound
high
alues
o
in es inal
an ibody
o
be alac oglobulin
and
o al-
bumin
in
un ea ed
coeliac
disease
pa ien s,
wi h
pe sis ence
o
IgM
an ibody
o
hese
p o eins
in
ea ed
pa ien s.
An ibodies
o
hese
ood
p o-
eins
we e
less
speci ic
o
coeliac
disease
han
an igliadin
an ibodies.
I
has
been
sugges ed
ha
high
alues
o
se um
an ibody
o
hese
p o eins
in
un ea ed
coeliac
disease
is
simply
he
esul
o
inc eased
in es inal
pe meabili y
o
an igens.
Al hough
ELISA
is
now
accep ed
as
he
s anda d
assay
echnique
o
measu ing
an i-
bodies
o
ood
p o eins
in
coeliac
disease,
se e al
di e en
ELISA
me hods
ha e
been
desc ibed,
and
di e en
e e ence
p epa a ions
a e
used
by
each
g oup
o
in es iga o s.
The
me hod
we
used
is
essen ially
simila
o
ha
o
Sa ilah i
e
al3
and
we
used
c ude
gliadin
as
an igen
o
he
ELISA
( a he
han
say,
alphagliadin),
as
Ske i
e
al2'
ha e
shown
ha
se a
and
in es inal
aspi a es
om
coeliac
pa ien s
con ain
an ibodies
which
bind
o
se e al
di e en
gliadin
subuni s.
We
ha e
no
asc ibed
le els
o
'posi i i y'
o
'nega-
i i y'
o
an ibody
alues;
such
a bi a y
designa-
ions
a e
o
some
alue
in
sc eening
es s
used
in
clinical
p ac ice
bu
no
in
p ospec i e
esea ch
in es iga ions.
Al hough
un ea ed
coeliac
disease
pa ien s
had
s a is ically
highe
alues
o
sali a y
IgA
and
IgG
an igliadin
an ibodies
compa ed
wi h
con-
ols,
sali a y
an ibodies
we e
gene ally
low
wi h
a
la ge
o e lap
be ween
pa ien s
and
con ols.
Fu he mo e,
he e
was
no
co ela ion
be ween
jejunal
aspi a e
and
sali a y
an ibody
alues.
Ou
esul s
do
no
sugges
ha
an ibody
es s
on
sali a
ha e
any
diagnos ic
o
sc eening
po en ial.
On
he
o he
hand,
gu
la age
o e s
a
ela i ely
non-in asi e
al e na i e
o
in uba ion
o
he
collec ion
o
in es inal
sec e ions
o
immunoglobulin
and
an ibody
s udies.
An i-
body
indings
in
gu
la age
luid
we e
b oadly
simila
o
hose
in
jejunal
aspi a e,
wi h
a
posi i e
co ela ion
o
IgA
an igliadin
an ibody
alues
in
hose
pa ien s
s udied
by
bo h
echniques.
Immunoglobulin
concen a ions,
howe e ,
di e ed
conside ably
in
jejunal
aspi a e
and
gu
la age
luid;
all
h ee
immunoglobulin
iso ypes
we e
aised
in
jejunal
aspi a e
in
he
un ea ed
coeliac
disease
pa ien s,
whe eas
only
IgM
was
signi ican ly
aised
in
gu
la age
luid.
Gu
la age
luid
is
likely
o
con ain
sec e ions
om
no
only
he
small
bowel
bu
also
gas ic
juice,
bile,
panc ea ic
sec e ions,
and
colonic
sec e ions.
In
his
espec ,
i
is
no
a
homogeneous
luid,
unlike
jejunal
aspi a e,
which
e lec s
e en s
in
he
jejunum
only,
and
is
hus
mo e
likely
o
ep esen
accu a ely
local
immune
phenomena
in
coeliac
disease.
Fluid
low
a e
is
ano he
ac o
ha
may
in luence
Ig
alues
in
exoc ine
sec e ions;
his
may
pa ly
accoun
o
di -
e ences
in
indings
in
jejunal
aspi a e
and
gu
la age
luid.
The
ele ance
o
glu en
eac i e
in es inal
B
cells
and
an ibodies
o
he
pa hogenesis
o
coeliac
disease
is
unce ain;
he
p esence
o
an ibodies
o
glu en
de i ed
p o eins
in
pa ien s
wi h
coeliac
disease
may
be
me ely
an
epiphe-
nomenon
in
he
con ex
o
a
T
cell
media ed
en e opa hy
wi h
expansion
o
he
ele an
popula ions
o
T
helpe
as
well
as
e ec o
cells.22
I
is
ce ainly
possible
ha
mucosal
IgM
an i-
body
is
immunopa hogenic,
o
example
by
ixing
complemen
in
he
immedia e
icini y
o
en e ocy es.
This
s udy
shows
he
dissocia ion
o
sys emic
and
in es inal
humo al
immune
esponses
in
pa ien s
wi h
coeliac
disease,
and
is
e idence
ha
o
he
s udy
o
immunopa hology
o
in es inal
disease,
di ec
in es iga ion
o
he
gu
is
manda o y.
M s
J
Johns one
and
M
N
Ande son
p o ided
echnical
assis-
ance.
This
wo k
was
unded
by
g an s
om
he
Sco ish
Hospi als
Endowmen
Resea ch
T us
(SHERT),
he
Na ional
Associa ion
o
Coli is
and
C ohn's
disease
(NACC),
he
Sandoz
ounda ion,
and
Fisons
pha maceu icals.
We
hank
he
nu sing
s a
o
he
GI
in es iga ion
sui e,
Wes e n
Gene al
Hospi al.
1
Unswo h
DJ,
Kie e
M,
Holbo ow
E,
Coombs
RRA,
Walke -Smi h
J.
IgA
an igliadin
an ibodies
in
coeliac
disease.
Clin
Exp
Immunol
1981;
46:
286-93.
2
O'Fa elly
C,
Kelly
J,
Hekkens
W,
e
al.
a-Gliadin
an ibody
le els:
a
se ological
es
o
coeliac
disease.
B
MedJ7
1983;
286:
2007-10.
3
Sa ilah i
E,
Pe kkio
M,
Kalimo
K,
Viande
M,
Vainio
E,
Reunala
T.
IgA
an igliadin
an ibodies:
a
ma ke
o
mucosal
damage
in
childhood
coeliac
disease.
Lance
1983;
i:
320-2.
4
Sco
H,
Fausa
0,
Ek
J,
B and zaeg
P.
Immune
esponse
pa e ns
in
coeliac
disease.
Se um
an ibodies
o
die a y
an igens
measu ed
by
an
enzyme-linked
immunoso ben
assay
(ELISA).
Clin
Exp
Immunol
1984;
57:
25-32.
5
Fe guson
A,
Ziegle
K,
S obel
S.
Rele ance
o
in es inal
mucosal
T-cells
in
he
immunology
o
coeliac
disease
and
ood
alle gy.
In:
Chadwick
VS,
ed.
Mechanisms
o
gas o-
zn es inal
in lamma ion.
Welwyn:
Smi h
Kline
and
F ench,
1984:
85-7.
6
Ma sh
MN.
Func ional
and
s uc u al
aspec s
o
he
epi helial
lymphocy e,
wi h
implica ions
o
coeliac
disease
and
opical
sp ue.
Scand3 Gas oen e ol
1985;
20
(suppl
114):
7
Fe guson
A,
MacDonald
TT,
McClu e
JP,
Holden
RJ.
Cell-
media ed
immuni y
o
gliadin
wi hin
he
small-in es inal
mucosa
in
coeliac
disease.
Lance
1975;
i:
895-7.
8
Bullen
AW,
Losowsky
MS.
Cell-media ed
immuni y
o
glu en
ac ion
III
in
adul
coeliac
disease.
Gu
1978;
19:
126-31.
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be ween
sys emic
and
mucosal
humo al
immune
esponses
in
coeliac
disease
35
9
Baklien
K,
B and zaeg
P,
Fausa
0.
Immunoglobulins
in
jejunal
mucosa
and
se um
om
pa ien s
wi h
coeliac
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ScandJGas oen e ol
1977; 12:
149-59.
10
Wood
GM,
Howdle
PD,
T eidosiewicz
LK,
Losowsky
MS.
Jejunal
plasma
cells
and
in
i o
immunoglobulin
p oduc-
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in
adul
coeliac
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Clin
Exp
Immunol
1987;
69:
123-32.
11
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A,
Ca swell
F.
P ecipi ins
o
die a y
p o eins
in
se um
and
uppe
in es inal
sec e ions
o
coeliac
child en.
B MedJ
1972;
i:
75-7.
12
Lab ooy
JT,
Hohmann
AW,
Da idson
GP,
He zel
PAS,
Johnson
RB,
Shea man
DJC.
In es inal
and
se um
an ibody
in
coeliac
disease:
a
compa ison
using
ELISA.
Clin
Exp
Immunol
1986;
66:
661-8.
13
Vol a
U,
Bonazzi
C,
Lazza i
R,
e
al.
Immunoglobulin
A
an igliadin
an ibodies
in
jejunal
juice:
ma ke s
o
se e e
in es inal
damage
in
coeliac
child en.
Diges ion
1988;
110:
85-91.
14
Mes ecky
J.
The
common
mucosal
immune
sys em
and
cu en
s a egies
o
induc ion
o
immune
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in
ex e nal
sec e ions.
J
Clin
Immunol
1987;
7:
265-76.
15
Gaspa i
MM,
B ennan
PT,
Solomon
SM,
Elson
CO.
A
me hod
o
ob aining,
p ocessing
and
analyzing
human
in es inal
sec e ions
o
an ibody
con en .
J
Immunol
Me hods
1988;
110:85-91.
16
Hohmann
A,
Lab ooy
J,
Da idson
JP,
Shea man
DJC.
Measu emen
o
speci ic
an ibodies
in
human
in es inal
aspi a e:
e ec
o
he
p o ease
inhibi o
phenyl-
me hyl
sulphonyl
luo ide.
J
Immunol
Me hods
1983;
64:
199-204.
17
Sco
H,
Ek
J,
B and zaeg
P.
Changes
o
se um
an ibody
ac i i ies
o
a ious
die a y
an igens
ela ed
o
glu en
wi hd awl
o
challenge
in
child en
wi h
coeliac
disease.
In
A ch
Alle gy
Appl
Immunol
1985;
76:
138-44.
18
Kilande
AF,
Nilsson
LA,
Gillbe g
R.
Se um
an ibodies
o
gliadin
in
coeliac
disease
a e
glu en
wi hd awal.
Scand
J
Gas oen e ol
1987;
22:
29-34.
19
Falchuk
ZM,
S obe
W.
Glu en-sensi i e
en e opa hy:
syn-
hesis
o
an i-gliadin
an ibody
in
i o.
Gu
1974;
15:
947-52.
20
Cicli e a
PJ,
Ellis
HT,
Wood
GM,
Howdle
PD,
Losowsky
MS.
Sec e ion
o
gliadin
an ibody
by
coeliac
jejunal
mucosal
biopsies
cul u ed
in
i o.
Clin
Exp
Immunol
1986;
64:
119-24.
21
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on Sep embe 1, 2020 a Uni e sidad de Valladolid. P o ec ed by copy igh .h p://gu .bmj.com/Gu : i s published as 10.1136/gu .32.1.29 on 1 Janua y 1991. Downloaded om