Chronic Teisintng experhamtai ,.,,teimmem mceOalomyeli~ tndeced by iojection of bca~ homogemae is ene of the best an~asi models for multiple sclerosis (MS) ...
153
W01.02
P10.01
A PEPTIDE FROM MYELIN OLIGODENDROCYTE GLYCOPROTEIN THAT INDUCES DEMYELINATING E N C E P H A L O M Y E L I T I S
FAILURE O F EAE D E V E L O P M E N T P R E - T R E A T E D PL/J MICE.
RESEMBLING MULTIPLE SCLEROSIS C.C.A. Bethel, T.G. Johns, N. KerMtode Rosbo and M. ldMImwa. Nemrolmmunology~ , La Trobe University, Bandeera, Victoria, 3083, Australia Chronic Teisintng experhamtai ,.,,teimmem mceOalomyeli~ tndeced by iojection of bca~ homogemae is ene of the best an~asi models for multiple sclerosis (MS). Howev~ it is still unclear which ant/gen(s) or combination o( ~mdgem in CNS bon~ogonate induce the demyeSu,tn$ immeee regmn~. Myelin oligodendrocyteglycowo~in (}dOG). a CNS-speolfic myelin component on the ontonmmt lamailae of myelin shead~ is comidefed as a putative ~rget antigen in multiple w.leaosis. ~ t, ~ and in viyo gudi~ have drown that entilxx~¢s to MOG can initiate extemive demyelimeim and we w,cenfly demonstraied a wedomtnant T cell response to MOG in a pupuintioa of MS patients. We now show that a single injection of a 21 ~ acid peptid¢ dedved fi'om the iemmtmoOobulin-tikedomain of MOO is able to produce a r e l a ~ g remitan" g nentologicai disemc with extemive MS plaquo-like demyeJlmtion in Lewig mrs. Onse.t of seve~'edisea~ clemty cotw.lsted with ine appearance of ~ antibody specific for the N-terminal of the peptidle. speciflcaily to MOG and had in v i ~ demyelianfingactivity. Tl~ d ~ o m t r a ~ involvementof MOG as a new nenral autoendgenmay provide a deeper insight into the pathogene~isof multiple sclerosis and its treatment.
IN A N T I - C D 4
mAb
G. Blasi*, A. Facchinutti% G. Monastra°, C. Ferrart*, S. 8ivieri ^, B.Tavolato^, and P. GalIo^ /n,~/tute o f F_xpwfmenfa/ PaOlofogy, University of Ancona* Insb'bJte of Otlcology" and ~ of Neurology.Second Neurologlc Clinic ^, Unlven#ty of Padove, ItMy. Our recent findings in adult mice showed that following antigen recognition under an umbrella of non-depleting anti-CD4 mAb (H129.19), immunological tolerance was produced by two consecutive signals UanemittlKI by CD4 and TCR molecules that produced T lymphocyte clonll deletion. To evaluutl MBP-toinrence, PL/J mice were pre-treut~l with H129.19 mAb, which causes CD4 receptor setml~on for 2-3 weeks, before MBP challange. Unlike MBP-injectsd conlrol mice which manifsst~i an acute EAE episode, mAb treated mice w ~ e fully prollctsd, and also resisted antigen re-challenge t month l a w when their CD4+ cells were not longer coated by mAb. In eddltion, superantigen SEB treatment two months later reinduced EAE in the control mice, but not in mAb tmutmd animals. These findings may suggest that MBP racognltion afinr antiCD4 mAb treatment Induces antigen-specific holes in the T cell repertoire.
for difficulties
lead to hazardous i d e n t i f i c a t i o n : IgG-PC0 anti-GMl is proved by IEF, problems a r i s e for IgM l i k e l y in E F - s e p e r a t i o n .
W06.03 A U T O R E A u H V E CD8 ÷ T C E L L RESPONSES T O H U M A N MYELIN PROTEIN-DERIVED PEPTIDES ~g~..BJiklil~. Tomiko Tsuchida I, John E. Coliganz, and Kenneth C. Parker2. INeuroimmunologyBranch, NINDS and 2Laboratory o f Molecular Structure, NXA]]), N ] ~ Betheeda, M D The ability o f self pcptides dc1"ived from human myelin proteins to induce autoreacdve CD8* T cell responses has benn a s ~ , ~ d . Peptide sequences from human myelin basic protein (MBP), proteolipid protein (PIP), myelin-associated glycoprotein (MAG), and myelin oligodendrocyte glycoprotein (MOG) have been identified that bind to and form stable complexes with HLA-A2. One MBP, one PLP, and three M A G peptides were all able to induce peptide-specific I-ILA-A2 restricted CD8+ CTL responses in vitro in HLA-A2÷ individuals. CTL clones reactive to the MBP and one o f the M A G peptides produced TNF--cL and a subset o f these clones also produced IFN-1,. These results demonstrate that: 1) self peptides derived from human myelin proteins can induce autoreactive CD$* CTL; and 2) these CD8 + T cells produce cytoldnes thought to be important in mediating demyelinating disease. These are the first studies that provide an experimental approach for the assessment of CD8 + T cell responses in such autoimmune diseases.
P14.02
P04.02
HAM/TSP: IMMUNE RESPONSE IN CEREBROSPINAL FLUID
INDIVIDUAL AND LONGITUDINAL EVALUATION OF OVERPRODUCTION OF FREE IMMUNOGLOBUUN UGHT CHAINS AS A SIMPLE CONTRIBUTION TO MS DIFFERENTIAL DIAGNOSIS
P13.02 ANTI-GMI ACTIVITY ANO PLASMACELL DYSCRA$1A (PCD) IN NEUROLOGICAL PATIENTS: IDENTICAL OR INDIPENDENT PHENOMENA? G.Bernardi, A.SohirIanzoni, S.Frigerio, C.Ariano, C.Terrani and A.Nespolo
lstituto ITALY.
Nazionale
Neurologico
D.Pareyson,
"C.Oesta",
Milano,
Former studies proved t h a t M p r o t e i n s with anti-GMl activity may cause p o l i n e u r o p a t i e s or MND. In this study we t r i e d to set up a symple method to r e l a t e e l e c t r o f o r e t i ¢ a b n o r m a l i t i e s and antibody a c t i v i t y .
POD was tested by IFE and i s o e l e c t r i c f o c o u s i n g
(IEF),
blotting and immunodetection ( I g 6 ) . Highly positive a n t i OMI samples ( E L I S A , R i t t e r ) , 1/50D d i l u t e d , were
incubated in OH1 coated and blank ELISA w e l l s , IEF run, b l o t t e d , a n t i - l g G or IgM peroxidase conjugated matched and chemi-luminescence detected; IgM e l e c t r o f o r e s i s was also performed. 7 p a t i e n t s (Z GMI+ PCD+,2 OH1* PCD-,2 OH1- PCD+. 1 GMI- PCD-) and ] controls (Z GMI+ PCD-. I GML- PCO-) were tested for lgG and 4 p a t i e n t s GMl+ PCD+ and 4 c o n t r o l s OMt- PCO+ were tested for
log
IgM,
bands disappeared a f t e r
a b s o r b t i o n only in
GMI+
patients. No a b s o r b t i o n appeared in monoclonal PCD+ OH1+ p a t i e n t s . PCO and a n t i - 6 M l a n t i b o d i e s in the same p a t i e n t
IgM may
easily
A I BHIGJEE I ' M K SHARIEF 2 j BILL P L A I I. Dept of Neurology, Univ. Of Natal South Africa. 2. Institute of Neurology, Queen Square, London. Introduction~ A study was undertaken to evaluate the CSF profile in patients with HAM/TSP in Natal, South Africa. Material & Methods: The IgG index was calculated in 63 patients and iso-electric focusing done in 36 samples. The serum and CSF 82 microglobulin (B2M) was measured in 25 paired samples. IL-2 & soluble IL-2 receptor levels were measured in 12 paired srum and CSF samples. Results: The IgG index was greater than 0.7 in 75% of the patients tested, whilst CSF IgG oligoclonal bands were detected in 30/36 (83%) samples. The CSF B2M was greater than serum B2M in 17/25 (68%) of samples. Nine patients had raised IL-2 in CSF and 10 raised CSF sIL-2R. CSF levels were higher than corresponding serum levels in all except in two patients. Conclusion: This study confirms a vigorous CSF immune response and provides indirect support for possible immune mediated damage in HAM/TSP
Boersma W.J.A., Deen C., Radl J.,'Buljevac D.,'Polman Ch., ""Revid R., Claassen E. TNO Prevention and Health, Div. Immunological and Infectious Diseases, PO Box 2215, 2301 Leiden, The Netherlands. "Erasmus university Rotterdam dept. Neurology, "Free University Amsterdam Dept. Neurology, --Dutch Brain Bank Amsterdam. Overproduction of immunoglobulin light chains may be associated with various stages of diseases including MS. Overproduction for kappa as well as for lambda light chains has been reported. We have developed new highly specific MAbs for ig light chains which in a capture ELISA allow accurate determination at nanogrem level of the presence of free and bound light chains in liquor, urine and sere, Liquor (n>30), serum (n>300) and urine (n>200) was collected (repeatedly) from MS patients in various stages of disease, from OND's and from normal controls In liquor and urine determinations of light chains was highly sensitive, concentrations of free light chains were compared to the concentration of intact IgG. Overproduction was mainly found in the lamboa compartment, though also for kappa incidentally overproduction was observed. Overproduction was observed for MS patients but incidentally also for non-MS patients. In eera background levels are higher than observed for other samples. However, also there overproduction was almost exclusively found in the lambda compartment. The implications for longitudinal application of this simple diagnostic tool will be evaluated.
