Læknablaðið - 15.03.1998, Qupperneq 45

LÆKNABLAÐIÐ 1998; 84
223
Nýr doktor í læknisfræði
Þann 14. febrúar 1998 varði
Kristján Steinsson doktorsrit-
gerð sína við læknadeild Há-
skóla íslands. Ritgerðin ber
nafnið Systemic Lupus Eryt-
hematosus. Epidemiology, Pat-
hogenesis and Genetics with
Special Reference to the Major
Histocompatibility Complex
and Complement Deficiency.
Agrip úr ritgerðinni fer hér á eft-
ir.
Systemic lupus erythematosus
(SLE) is the prototype for systemic autoim-
mune diseases. Epidemiological and genetic
data suggest that expression of this disease ref-
lects a complex interplay between numerous
genetic and environmental factors. This thesis
deals with the epidemiology and psychiatric
manifestations, the role of complement defici-
ency, and the relative contribution of major hi-
stocompatibility alleles to the pathogenesis in
SLE patients in Iceland.
The epidemiological study is the only
nationwide survey where strict criteria were
applied for the classification of SLE. The value
of the study lies in its unselected nature and the
application of widely accepted criteria to
define SLE. Over a 10 year period (1975-1984)
seventy-six new cases were found with an inci-
dence of 5.9 and 0.8/100,000 for females and
males. The mean age at diagnosis was higher
than in many previous studies and a clinical
pattern different from most previous studies
was found, as illustrated by a low incidence of
renal disease. These findings may reflect the
unselected nature of the study, racial differ-
ences or milder SLE disease manifestations in
recent years. Comparison with a former study
on SLE in Iceland shows an actual increase in
incidence.
The study of the psychiatric manifestations
has relatively little referral bias and is probably
more representative than most previous stu-
dies. A high prevalence of phobias in the SLE
patients as compared to a population control
group was observed.
The first documented report of the associ-
ation of SLE and complete Clq deficiency is
presented. This report was the
impetus to further studies of the
role of complement deficiency in
the pathogenesis of SLE. The ex-
perience of plasma replacement
therapy in a C2 deficient patient
is reported. This novel therapy
was strikingly successful. The
findings further support a causal
relationship between complement
deficiency and immune complex
disease and may lead to more tar-
geted treatment interventions.
The relative contribution of single MHC all-
eles to the pathogenesis of SLE was examined.
MHC class II alleles and C4 allotypes were
determined in 64 Icelandic patients and in an
ethnically matched control group. The frequen-
cy of C4AQ0 was significantly higher in pati-
ents than in controls. HLA-DRBL DQAl and
DQBl alleles were not significantly different
from those of controls. On the other hand, an
increase in DRB1*03 was observed in the
group of patients with C4AQ0. Following
these results a large multicase SLE family was
studied clinically and typed for MHC class II
and C4 allotypes. C4AQ0 is highly associated
with morbidity in this family. However, the
C4AQ0 is carried on 5 different haplotypes of
which 4 were found in the patients with SLE.
Two of the C4AQ0 bearing haplotypes run
through the family line; the other 3 originate
from the spouses. Three of the 5 C4AQ0 bear-
ing haplotypes shared the fragment B8, Cw7,
C4AQ0, C4B1.
The results are consistent with the argument
that C4A deficiency contributes independently
to susceptibility of SLE. C4AQ0 in SLE pati-
ents in Iceland shows less marked linkage
disequilibrium with other MHC alleles than
reported in most other studies on Caucasian
populations and emphasizes the role of et-
hnicity.
In progress are studies of a number of
Icelandic families with multiple SLE cases in-
volving genotyping and allotyping of C4 and
other candidate genes as well as a genome-
wide scanning for the determination of
susceptibility loci.