Læknablaðið : fylgirit - 01.05.1978, Page 41

Henée Norberg and P.O. Gedda
Department of Immunology. The National
Bacteriologieal Laboratory, Stockholm and
Department of Rheumatology, Central County
Hospital, Örebro, Sweden.
Circulating IgG complexes, particularly inter-
mediate complexes with sedimentation coefficients
between 11S and 19S are frequently found in
rheumatoid arthritis (2,4). We have been inter-
ested in studying the behaviour of these complexes
during penicillamine therapy.
Material and methods:
The present clinical material was from the
Swedish county hospital in Örebro. 56 patients
were treated for at least 4 months during a
period of 12 months. The patients were regularly
examined clinically and bloodsamples were drawn
before therapy and then monthly. Control sera
were obtained from healthy personnel.
The amounts of IgM. IgG and IgA were
determined by the Mancini method (3).
IgM-RF:s were detected by human, blood
group O, erythrocytes, sensitized by rabbit
amboceptor.
Quantitative latex fixation test was
performed with microequipment utilizing Ilyland
RA-latex suspension diluted 1:4 in 0.1 M borate
buffer, pH8.2.
The ability of serum to bird 125j
labelled Clq was tested by the method of
Ifydegger et al. (5).
Sera from 20 patients randomly selected were
subjected to gradient centrifugation.
The sedimentation analysis was performed in a
Spinco SW50 rotor at 25,000 rpm for 18 hr at
4°C. Serum, 0.5 ml diluted 1:6, was layered
over a continuous gradient of sucrose ranging
from 107o to 377o in 0.1 M phosphate buffer pH
7.2 (total volume 5 ml). 70-80 cerial fractions
were collected dropwise from the bottom and
the IgG and IgM levels were determ.veed in every
second fraction.
Results and discussion:
The efi'ect of 4 months of therapy was good
or excelleat in 49 patients (75%). Since cnly
patients who had tolerated penicillamine-therapy
for at least 4 months were included, the cxact
number of patients with therapeutie side-effecte
cannot be ruled out. later on, however,
penicillamine had to be withdrawn in 12 out oí
the 66 patients, mostiy because of thrombocy-
EFFECTS ON CIRCULATING
IGG COMPLEXES
IN RHEUMATOID
ARTHRITIS BY TRfeATMENT
WITH PENICILLAMINE
topenia and renal symptoms. There were no
significant changes of the mean IgM and IgG
values, although marked inriividual decreased
were observed. The mean IgA level decreased
significantly and so did the latex titres.
Increased Clq-binding capacity of serum lias
been utilized as a sensitive test for detecting
circulating immune complexes. The complexes
must have a certain size to be able to bind Clq
and it is probable that the smallest IgG complexes
consisting ol' 2 - 3 IgG molecules will not bind
Clq. However, 31 out of the 66 sera had before
therapy an increased Clq-binding capacity and
aftcr 4-6 months of therapy, 24 cf them were
normalized. This might indicate dicappearance
of complexes during thcrapy.
Before therapy, 14 out of the 20 sera, selected
for gradient centrifugation analysis, had signs of
IgG complexes.
IgG of control sera was found in a main peak
corresponding to 7S (fig.l), whereas in RA small
amounts of IgG were found in fractions corre-
sponding to sedimentation coefficients >7S (fig. 2a).
The IgG complexes seemed to have disappeared
already after a month of penicillamine therapy i 1
some sera (fig. 2b) and were still r 'cent after
longer periods of treatment (fig. 2c, 3, 4, and 5).
Penicillamine had to be withdrawn in about ono
fourth of the patients on account of side-effects
and íig. 6 shows the gradient centrifugaticn of
serii fi om a patient ín whom tlie therapy was
ceased after 5 months. The intermediate IgG
complexes proved before therapy hád disappeared
at time for withdrawal but seemed to be back in
the sample drawn 8 months later.
The IgG complexes found in sera from patients
in whom penicillam ine had no tlierapeutic effect
seemed to remain imaffected even affer several
ínonths oí therapy (fig. 7).
Thus thc behaviour of tiie circulating IgG
complexcs correlated wtll wi.th the therapeutic
results of penicillamine.
Moreover, consistent rotnits iiavt been published
b/ Jafíe (I;.
TIio IgG con.ulexes were íot dissociated by
peniciliamine in vitro. Tlic mode of action in
vivo ís not anown lmt penicillamine might ha*'e
sn iuúbitorv cffcct or, the IgG cornnlex formation
ít the eollular Itvel.