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DOI: 10.1055/s-2001-17114
Neue immuntherapeutische Strategien bei Autoimmunerkrankungen
New strategies in the immunotherapy of autoimmune diseaesPublikationsverlauf
Publikationsdatum:
13. September 2001 (online)

Obwohl intensive Forschungsarbeiten zur Pathogenese von Autoimmunerkrankungen wertvolle Details über Entstehung dieser Autoimmunopathien hervorgebracht haben, sind die zur Erkrankung führenden Mechanismen immer noch nicht komplett verstanden. Bei einigen Autoimmunopathien ist zumindest das Autoantigen bekannt (M. Basedow: TSH-Rezeptor; Myasthenia gravis: Azetylcholinrezeptor; Multiple Sklerose: myelin basic protein), wohingegen für die meisten der anderen Autoimmunopathien nur vereinfachende Vorstellungen und hypothetische Szenarien zur Pathogenese größtenteils kontrovers diskutiert werden. Die Beteiligung immunkompetenter Zellen bei der Initiierung und/oder Perpetuierung der Erkrankungen ist jedoch allgemein akzeptiert.
Die molekularen Mechanismen der Aktivierung dieser immunkompetenten Zellen werden immer besser verstanden. Vor diesem Hintergrund sind vor allem in der vergangenen Dekade viele Therapiestudien unternommen worden, die die therapeutische Anwendbarkeit eines spezifischen Eingriffs in die proinflammatorischen Reaktionskaskaden mit Immunbiologika wie den TNF-α neutralisierenden Antikörpern bei unterschiedlichen Autoimmunopathien untersucht haben. Die wegen des aggressiven Verlaufs und der hohen Prävalenz am meisten studierten Modellerkrankungen sind dabei die rheumatoide Arthritis (RA) und der M. Crohn (MC), auf die in dieser Übersicht exemplarisch und schwerpunktmäßig eingegangen werden soll. Basierend auf den erfolgreichen neuen Therapieformen werden inzwischen auch andere chronisch entzündliche Erkrankungen mit Immunbiologika behandelt. Hierbei liegen ermutigende Erfahrungsberichte vor. Nicht näher kann aus Platzgründen auf immuntherapeutische Ansätze (Therapie mit Interferonen, Interleukinen, Antikörpern) bei hämatoonkologischen (siehe hierzu den Beitrag von Jäger et al. in diesem Heft) oder allergologischen Erkrankungen oder auch neurologischen Autoimmunopathien wie der multiplen Sklerose eingegangen werden.
Literatur
- 1
Bresnihan B, Alvaro-Gracia J M, Cobby M. et al .
Treatment of rheumatoid arthritis with
recombinant human interleukin-1 receptor antagonist.
Arthritis Rheum.
1998;
41
2196-2204
Reference Ris Wihthout Link
- 2
Cannon G W. et al .
Prospective 5-year follow-up of recombinant
IFN-gamma in rheumatoid arthritis.
J Rheumatol.
1993;
20
1867-1873
Reference Ris Wihthout Link
- 3
Charles P J, Elliott M J, Feldmann M, Maini R N.
Development
of anti dsDNA antibodies in patients with rheumatoid arthritis treated
with a chimeric monoclonal antibody to TNF alpha.
EULAR
J.
1995;
24
B114
Reference Ris Wihthout Link
- 4
Cohen R D.
Efficacy
and safety of repeated infliximab infusions for Crohn’s
disease.
Inflamm Bowel Dis.
2001;
7
S17-22
(Suppl1)1)
Reference Ris Wihthout Link
- 5
Cornillie F. et al .
Infliximab induces potent anti-inflammatory
and local immunomodulatory activity but no systemic immune suppression
in patients with Crohn’s disease.
Aliment Pharmacol
Ther.
2000;
15
463-473
Reference Ris Wihthout Link
- 6
Elliott M J, Maini R N, Feldmann M. et al .
Randomised double-blind comparison of chimeric
monoclonal antibody to tumor necrosis factor α (cA2) versus
placebo in Rheumatoid Arthritis.
Lancet.
1994;
344
1105-1110
Reference Ris Wihthout Link
- 7
Fedorak R N, Gangl A, Elson C O. et al .
Recombinant human interleukin 10 in the
treatment of patients with mild to moderately active Crohn’s
disease.
Gastroenterology.
2000;
119
1473-1482
Reference Ris Wihthout Link
- 8
Finck B. et
al .
A phase III trial of etanercept vs. methotrexate
in early rheumatoid arthritis (Enbrel ERA trial).
Arthritis
Rheum.
1999;
42
S117
Reference Ris Wihthout Link
- 9
Harris E D.
Rheumatoid
arthritis.
N Engl J Med.
1990;
322
1277-1283
Reference Ris Wihthout Link
- 10
Hofschneider P H. et al .
Double-blind controlled phase III multicenter
clinical trial with interferon γ in rheumatoid arthritis.
Rheumatol
Int.
1992;
12
175-185
Reference Ris Wihthout Link
- 11
Kalden J R, Lorenz H M.
Rheumatoide
Arthritis. Blockade des Tumor-Nekrose-Faktor-α als therapeutisches
Prinzip.
Dtsch Ärztebl.
2001;
16
C847-848
Reference Ris Wihthout Link
- 12
Kavanaugh A, Schaible T. et al .
Long-term
follow-up of patients treated with infliximab in clinical trials.
Arthritis
Rheum.
1999;
42
S401
Reference Ris Wihthout Link
- 13
Landewe R BM. et al .
The distribution of malignant neoplasms
in rheumatoid arthritis is skewed compared to the general population.
Arthritis
Rheum.
1999;
42
S279
Reference Ris Wihthout Link
- 14
Lipsky P E, van der Heijde D M. et al .
Infliximab
and methotrexate in the treatment of rheumatoid arthritis.
N
Engl J Med.
2000;
343
1594-1602
Reference Ris Wihthout Link
- 15
Lipsky P E, van der Heijde D M. et al .
102
week clinical and radiological results from the ATTRACT trial.
Arthritis
Rheum.
2000;
43
S269
Reference Ris Wihthout Link
- 16
Lorenz H -M, Antoni C, Valerius T. et al .
In vivo blockade of TNF-alpha by i. v. infusion
of a chimeric, monoclonal TNF-alpha antibody in patients with rheumatoid
arthritis.
J Immunol.
1996;
156
1646-1653
Reference Ris Wihthout Link
- 17
Lorenz H M, Kalden J R.
Zytokin- und
Antizytokintherapie bei der rheumatoiden Arthritis.
Internist.
2001;
42
55-63
Reference Ris Wihthout Link
- 18
Lovell D J, Giannini E H. et al .
Etanercept
in children with polyarticular juvenile rheumatoid arthritis.
N
Engl J Med.
2000;
342
763-769
Reference Ris Wihthout Link
- 19
Maini R, St Clair E W, Breedveld F. et al .
Infliximab
(chimeric anti-tumour necrosis factor alpha monoclonal antibody)
versus placebo in rheumatoid arthritis patients receiving concomitant
methotrexate: a randomised phase III trial. ATTRACT Study Group.
Lancet.
1999;
354
1932-1939
Reference Ris Wihthout Link
- 20
Maini R N, Paulus H, Breedveld F C. et al .
rHUIL-10 in subjects with rheumatoid arthritis.
Arthritis
Rheum.
1997;
40
S224
Reference Ris Wihthout Link
- 21
Maini R V, Breedveld F C, Kalden J R. et al .
Therapeutic efficacy of multiple intravenous
infusions of anti-Tumor Necrosis Factor α monoclonal antibody combined
with low-dose weekly methotrexate in Rheumatoid Arthritis.
Arthritis
Rheum.
1998;
41
1552-1563
Reference Ris Wihthout Link
- 22
Mease P J, Goffe B S. et al .
Etanercept
in the treatment of psoriatic arthritis and psoriasis: a randomised
trial.
Lancet.
2000;
356
385-90
Reference Ris Wihthout Link
- 23
Moreland L M. et al .
Long-term use of etanercept in patients
with DMARD-refractory rheumatoid arthritis.
Arthritis
Rheum.
1999;
42
S401
Reference Ris Wihthout Link
- 24
Moreland L W, Baumgartner S W, Schiff M H. et al .
Treatment of rheumatoid arthritis with
a recombinant human tumor necrosis factor (p75)-Fc fusion protein.
N
Engl J Med.
1997;
337
141-147
Reference Ris Wihthout Link
- 25
Moreland L W, Morgan E E. et al .
T
cell receptor peptide vaccination in rheumatoid arthritis.
Arthritis
Rheum.
1998;
41
1919-1929
Reference Ris Wihthout Link
- 26
Moreland L W. et al .
Etanercept therapy in rheumatoid arthritis.
A randomized, controlled trial.
Ann Intern Med.
1999;
130
478-486
Reference Ris Wihthout Link
- 27
Pincus T, Callaghan L F.
Taking mortality
in rheumatoid arthritis seriously.
J Rheumatol.
1986;
13
841-845
Reference Ris Wihthout Link
- 28
Pincus T, Marcum S B, Callahan L F.
Longterm
drug therapy for rheumatoid arthritis in seven rheumatology private
practices: II. Second line drugs and prednisone.
J Rheumatol.
1992;
19
1885-1894
Reference Ris Wihthout Link
- 29
Present D H, Rutgeerts P, Targan S. et al .
Infliximab for the treatment of fistulas
in patients with Crohn’s disease.
N Engl J Med.
1999;
340
1398-1405
Reference Ris Wihthout Link
- 30
Rankin E C, Choy E H, Kassimos D. et al .
The therapeutic effect of an engineered human
anti-tumor-necrosis factor alpha antibody (CDP571) in rheumatoid arthritis.
Br
J Rheumatol.
1995;
34
334-342
Reference Ris Wihthout Link
- 31
Rau R, Herborn G, Sander O. et al .
Long-term
treatment with the fully human anti-TNF antibody D2E7 slows radiographic
disease progression in rheumatoid arthritis.
Arthritis
Rheum.
1999;
42
S400
Reference Ris Wihthout Link
- 32
Ricart E, Panaccione R. et al .
Infliximab
for Crohn’s disease in clinical practice at the Mayo Clinic.
Am
J Gastroenterol.
2001;
96
722-729
Reference Ris Wihthout Link
- 33
Rutgeerts P, D’Haens G, Targan S. et al .
Efficacy and safety of retreatment with anti-tumor
necrosis factor antibody (infliximab) to maintain remission in Crohn’s
disease.
Gastroenterology.
1999;
117
761-769
Reference Ris Wihthout Link
- 34
Sandborn W J. et al .
An engineered human antibody to TNF (CDP571)
for active Crohn’s disease.
Gastroenterology.
2001;
120
1330-1338
Reference Ris Wihthout Link
- 35
Schattenkirchner M. et al .
Efficacy and tolerability of weekly subcutaneous injections
of the fully human anti-TNF-antibody D2E7 in patients with rheumatoid
arthritis.
Arthritis Rheum.
1998;
41
S57
Reference Ris Wihthout Link
- 36
Schiff M, Furst D. et al .
The efficacy
and savety of pegylated recombinant methionyl human soluble tumor
necrosis factor receptor type I (PEG-sTNF-R I; p55) in a randomized,
placebo-controlled clinical study of patients with rheumatoid arthritis
(RA).
Ann Rheum Dis.
2001;
60
167
Reference Ris Wihthout Link
- 37
Schmeling H, Mathony K. et al .
A combination
of etanercept and methotrexate for the treatment of refractory juvenile
idiopathic arthritis.
Ann Rheum Dis.
2001;
60
410-412
Reference Ris Wihthout Link
- 38
Schreiber S, Campieri M. et al .
Use
of anti-tumour necrosis factor agents in inflammatory bowel disease.
Int
J Colorectal Dis.
2001;
16
1-11
Reference Ris Wihthout Link
- 39
Schreiber S. et al .
Safety and efficacy of recombinant human
interleukin 10 in chronic active Crohn’s disease.
Gastroenterology.
2000;
119
1461-1472
Reference Ris Wihthout Link
- 40
Sigidin Y A, Loukina G V, Skurkovich S V, Skurkovich B S.
Double-blind,
placebo-controlled study of antibodies to Interferon-α versus
antibodies to TNF-α in rheumatoid arthritis.
Arthritis
Rheum.
2000;
43
S290
Reference Ris Wihthout Link
- 41
Smolen J S, Breedveld F C, Burmester G R. et al .
Consensus statement on the initiation and
continuation of tumour necrosis factor blocking therapies in rheumatoid
arthritis.
Ann Rheum Dis.
2000;
59
504-505
Reference Ris Wihthout Link
- 42
Stack W A, . et al .
Randomised controlled trial of
CDP571 antibody to tumour necrosis factor-alpha in Crohn’s
disease.
Lancet.
1997;
349
521-524
Reference Ris Wihthout Link
- 43
Tak P P, ‘t Hart B A, Kraan M C, Jonker M, Breedveld F C.
The
effects of interferon b treatment on arthritis.
Arthritis
Rheum.
1998;
41
S56
Reference Ris Wihthout Link
- 44
Targan S R, Hanauer S B. et al .
A
short-term study of chimeric monoclonal antibody cA2 to tumor necrosis
factor alpha for Crohn’s disease. Crohn’s Disease
cA2 Study Group.
N Engl J Med.
1997;
337
1029-1035
Reference Ris Wihthout Link
- 45
van de Putte L BA. et al .
Efficacy of the fully human anti-TNF antibody
D2E7 in rheumatoid arthritis.
Arthritis Rheum.
1999;
42
S400
Reference Ris Wihthout Link
- 46
van de Putte L BA, van Riel P LCM, den Broeder A. et al .
A single dose placebo controlled
phase I study of the fully human anti-TNF-antibody D2E7 in patients
with rheumatoid arthritis.
Arthritis Rheum.
1998;
41
S57
Reference Ris Wihthout Link
- 47
van den Bosch F. et al .
rhuIL-4 in subjects with active rheumatoid
arthritis.
Arthritis Rheum.
1998;
41
S56
Reference Ris Wihthout Link
- 48
van der Heijde D M, van Leeuwen M A, van Riel P L, van de Putte L B.
Radiographic
progression on radiographs of hands and feet during the first 3
years of rheumatoid arthritis measured according to Sharp’s
method (van der Heijde modification).
J Rheumatol.
1995;
22
1792-1796
Reference Ris Wihthout Link
- 49
van Deventer S J, Elson C O, Fedorak R N.
Multiple
doses of intravenous interleukin 10 in steroid-refractory Crohn’s
disease. Crohn’s Disease Study Group.
Gastroenterology.
1997;
113
383-389
Reference Ris Wihthout Link
- 50
van Dullemen H M, van Deventer S J, Hommes D W. et al .
Treatment of Crohn’s disease with
anti-tumor necrosis factor chimeric monoclonal antibody (cA2).
Gastroenterology.
1995;
109
129-135
Reference Ris Wihthout Link
- 51
Weinblatt M E. et al .
A trial of etanercept, a recombinant tumor
necrosis factor receptor:Fc fusion protein, in patients with rheumatoid
arthritis receiving methotrexate.
N Engl J Med.
1999;
340
253-259
Reference Ris Wihthout Link
- 52
Weinblatt M E. et al .
Long-term savety and efficacy of combination
therapy with methotrexate and etanercept.
Arthritis Rheum.
1999;
42
S401
Reference Ris Wihthout Link
- 53
Wendling D. et al .
Treatment of severe Rheumatoid Arthritis
by anti-interleukin 6 monoclonal antibody.
J Rheumatol.
1993;
20
259-262
Reference Ris Wihthout Link
Korrespondenz
Priv.-Doz. Dr. med. Hanns-Martin Lorenz
Abt. für Rheumatologie, Institut für
Klinische Immunologie, Medizinische Klinik III, Universität
Erlangen-Nürnberg
Krankenhausstraße 12
91054 Erlangen
Telefon: 09131/853-6387/-9107
Fax: 09131/853-4770
eMail: Hannes.Lorenz@med3.imed.uni-erlangen.de