Zeitschrift für Rheumatologie – Supplement 1 - Deutsche ...

face of antigen presenting cells. Antibodies against mutated citrullinated
vimentin (MCV) have reportedly high specifi ty for RA.
Objective: Th e aim of our study was to test the diagnostic sensitivity
of anti-MCV compared to anti-CCP (against cyclic citrullinated peptides)
in patients with RA. Methods:Serum levels of anti-MCV were
measured in 84 patients with RA (diagnosed according to the ACR criteria),
m/f: 13/71; age (median) 63 yrs, the mean disease duration was
7 years. Th e examination consisted of the determination of ESR, CRP,
anti CCP antibodies, rheumatoid factor (RF) and blood count. Additionally
clinical assessment of the disease status (tender and swollen joint
count, disease activity score (DAS), Ritchie Index) and of radiological
destruction calculated by the Larsen score were performed. ELISAtests
were used to detect MCV and anti-CCP levels.Results:In our 84
patients with RA we measured CRP levels from 0–200 mg/dl (median:
13), ESR from 2-103 mm/1h (median 21mm/1h), RF levels from 0-1873
U/l median 38 U/l), We found a disease activity calculated by the original
DAS from 1,98–6,24 (median 3,23) and a Larsen score from 0–159
pts (median 44,9 pts). We detected anti-MCV levels(cut-off level. 50
U/ml) from 0,86 to 1469,5 U/ml (median 80,5) and anti-CCP levels
from 1,2–1600 U/ml (median 245,7 ). Th e sensitivity of anti-MCV for
RA was calculated with 69 %, the sensitivity of anti-CCP with 67,9%
and of RF 52,9%. Patients were divided into three groups according to
their disease activity score (DAS): patients with mild activity (DAS<
2,6), moderate activity (DAS 2,6-5,1) and high activity (DAS > 5,1). We
found a signifi cant correlation between anti-MCV and DAS (p=0,04;
0,9981). Th e correlations with age, disease duration, CRP and radiological
destruction were not signifi cant. A division into groups with
diff erent DMARD therapies was not useful.
Conclusion: RA is associated with antibodies like rheumatoid factor
and anti-CCP antibodies .Anti-MCV was detected fi rst as Sa – antigen
and is known as antibody with a high specifi city to RA. In our study
the sensitivity of anti-MCV was calculated with 69%, compared to anti
– CCP with 67,9%. Anti-MCV correlates also with disease activity and
appears to be a new and important marker for the diagnosis of RA.
Further studies have to be designed to show the value of this new parameter
as a predictive parameter for the clinical outcome in patients
with RA.
POFER-9
Presence of Chromaffi n-like Cells in Synovial Tissue from Rheumatoid
Arthritis (RA) Patients
Capellino S., Härle P., Pongratz G., Falk W., Straub RH.
Department of Internal Medicine I, University Hospital of Regensburg,
93042 Regensburg
Objective: It is known that norepinephrine (NE) can infl uence the immune
response with anti-infl ammatory eff ects at high concentrations.
We demonstrated a loss of sympathetic nerve fi bers in synovial tissue
from patients with RA (not osteoarthritis, OA). However, there is no
diff erence in NE release from synovial tissues in RA vs. OA. Th is study
aimed to investigate cells involved in NE production in RA tissue.
Methods: Synovial samples were obtained from 10 OA and 10 RA
patients during knee joint replacement surgery. Staining of tyrosine
hydroxylase (TH), tyrosinase (Tyr), DOPA-decarboxylase, dopamine
beta hy-droxylase (DBH), PNMT and COMT (key enzymes of catecholamine
production and degradation), and of PGP9.5 and SV2A
(marker of chromaffi n cells) were performed by immunofl uorescence
(IF).
Results: In RA compared to OA, we found a signifi cantly higher
amount of cells expressing TH, Tyr, DOPA-decarboxylase and DBH.
However, there was no signifi cant diff erence in the number of cells
expressing PNMT and COMT (enzymes for NE degradation). In RA
patients, we also found cells expressing PGP 9.5, a typical marker of
chromaffi n cells. Th ese cells did not double stain with macrophages, fi -
broblasts, B cells, and T cells, but were also positive for TH and SV2A,
two other markers of chromaffi n cells. Interestingly, we did not fi nd
these cells in OA patients.
Conclusions: We hypothesize that chromaffi n cells appear in RA synovial
tissue. We are presently studying these cells in the context of
infl ammation in order to understand the origin of these cells and to
characterize their infl uence on the infl ammatory process.
POFER-10
Pro- and antiinfl ammatory functions of CCR2 in collagen-induced
arthritis
Brühl H. 1 , Cihak J. 2 , Plachy J. 3 , Stangassinger M. 2 , Mack M. 4
1 Department of Internal Medicine I, University of Regensburg, 2 Institute
for Animal Physiology, University of Munich, 3 Institute of Molecular
Genetics, Czech Academy of Sciences, Prague, 4 Department of Internal
Medicine II, University of Regensburg
To evaluate CCR2 as a potential target in arthritis, we studied its
expression on diff erent murine leukocyte subsets and the eff ect of
a monoclonal anti-CCR2 antibody (MC-21) in vitro and in the progression
phase of collagen induced arthritis. CCR2 is expressed
on three cell populations: 1. CD25+ CD44+ regulatory T cells
(J Immunol 2004, Brühl et al). 2. Gr1+ proinfl ammatory monocytes
but not on Gr1- monocytes. Application of low doses of MC-21 in vivo
(10 μg i.p.) results in a transient (1day) complete depletion of Gr1+
proinfl ammatory monocytes. 3. CCR2 is expressed on basophils. MC-
21 stimulates the release of cytokines from basophils in vitro. In vivo,
the MC-21 induced release of cytokines is dose dependent as only high
doses of MC-21 (50-100 μg) result in a cytokine release while low doses
(10 μg) have no eff ect.
We therefore decided to treat mice during progression of collagen
induced arthritis with daily injections of low (10 μg) or high (50 μg)
doses of the CCR2 antibody MC-21. Injection of high doses of MC-21
resulted in a marked aggravation of arthritis, while injection of low
doses signifi cantly reduced arthritis even during disease progression.
Th ese results show that the CCR2 antibody MC-21 has pro- and antiinfl
ammatory eff ects in vivo. Depletion of proinfl ammatory monocytes
can be achieved by daily injections of low doses of MC-21 thereby
preventing the activation and the cytokine release from basophils.
Low doses of MC-21 are not suffi cient to deplete CCR2+ regulatory T
cells. Th ese data open new possibilities for CCR2 based therapies of
arthritis and help to avoid negative eff ects of CCR2 antibody treatments.
POFER-11
Infl uence of TNF-a and IL-1b on matrix degradation by synovial
fi broblasts in an in vitro cartilage/ pannus model
Pretzel D. 1 , Pohlers D. 1 , Mollenhauer J. 2 , Richter W. 3
1 Experimental Rheumatology Unit, Department of Orthopedics
Friedrich-Schiller-University Jena, 2 Research Department, Waldkrankenhaus
Rudolf Elle, Eisenberg, 3 Center for Electron Microscopy, Friedrich-
Schiller-University Jena
Background: Aggressive synovial fi broblasts (SF) at the cartilage/pannus-junction
play an important role in joint destruction/infl ammation
in rheumatoid arthritis (RA). Th ey locally express tissue-destructive
enzymes (e.g. MMPs) and contribute to joint destruction. In vivo, SF
and articular chondrocytes are stimulated by cytokines and/or cell-cell
contact with infi ltrating infl ammatory cells.
Objective: To analyze the infl uence of stimulation on SF from (RA),
osteoarthritis (OA) and joint trauma (JT) with the proinfl ammatory
cytokines TNF-α and IL-1β in an in vitro co-culture system with bovine
articular cartilage (BC) explants. Methods:BC discs were embedded
in 48 well plates containing agarose. RA-, OA-, and JT-SF (n= 5
each) were co-cultured with BC for 2 weeks and treated with TNFα(10
ng/ml), IL-1β(5 ng/ml) or TNF-α/ IL-1β. Alteration of the BC was
Zeitschrift für Rheumatologie · Supplement 1 · 2006 | S77