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Vorstellungen zur Pathogenese der juvenilen idiopathischen Arthritis

Concepts on the pathogenesis of juvenile idiopathic arthritis

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Zusammenfassung

Zur Entstehung der juvenilen idiopathischen Arthritis (JIA) gibt es verschiedene Erklärungsansätze.

Es gibt es Hinweise, dass Veränderungen in Genen des Immunsystems zur JIA prädisponieren können und die Regulation des Immunsystems bei der Pathogenese von entscheidender Bedeutung ist. Vermutlich kommt dem adaptiven, erworbenen Immunsystem die zentrale Rolle zu. So ist bei der JIA eine auffällige Population von hoch aktivierten T-Zellen in der Synovia zu finden. Auch B-Zellen sind beteiligt, worauf die positiven ANA-Titer bei der JIA hinweisen. Regulatorische T-Zellen (Tregs) versuchen, die Expansion autoreaktiver T-Zellen zu unterbinden und haben eine protektive Funktion.

Aber auch das natürliche oder angeborene Immunsystem spielt eine Rolle. So könnte als Ursache der JIA mit systemischem Beginn eine Störung des Inflammasoms zugrunde liegen. Beim Zusammenspiel zwischen angeborenem und adaptivem Immunsystem zeigt sich, dass eine eindeutige räumliche und zeitliche Trennung zwischen natürlichem und adaptivem Immunsystem zunehmend schwieriger wird. Infektions- und virengetriggerte Immunreaktionen könnten ebenfalls eine Ursache der JIA sein. Eine nachgewiesen entscheidende Bedeutung für die Pathogenese haben proinflammatorische Zytokine, wie sie z. B. auch unter Stress ausgeschüttet werden.

Die neuen Techniken der Genomik und Proteomik können ein individualisiertes Profil für jeden Patienten erstellen und ermöglichen eine immer feinere Auftrennung von Subtypen und werden damit die therapeutischen Möglichkeiten verbessern.

Abstract

There are various explanations for the development of juvenile idiopathic arthritis (JIA).

Gene changes in the immune system can predispose to JIA and regulation of the immune system is crucial in the pathogenesis. The adaptive, acquired immune system probably plays a central role. Thus, in the case of JIA a conspicuous population of highly activated T-cells can be found in the synovia. B-cells are also involved, as indicated by positive ANA titers in JIA patients. Regulatory T-cells (Tregs) attempt to prevent the expansion of autoreactive T-cells.

However, the natural or the innate immune system also plays a role. Thus a disorder of the inflammasome could underlie the cause of JIA with systemic onset. The interaction between congenital and adaptive immune system shows that a distinct spatial and temporal separation between the two immune systems is becoming increasingly difficult. An infection- and virus-related immune reaction could also be the cause of JIA. Proinflammatory cytokines are of proven significance in pathogenesis in terms of how they are released under stress, for example.

New genomic and proteomic techniques are able to produce individualized profiles for each patient and allow for increasingly fine separation between subtypes, thus improving therapeutic possibilities.

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Abbreviations

AK:

Antikörper

ALPS:

Autoimmunes lymphoproliferatives Syndrom

ANA:

Antinukleäre Antikörper

AP-I:

„Activating protein-1“

ASC:

„Apoptosis-associated Speck-like protein containing a CARD“

CARD:

„Caspase recruitment domain“

CCR:

Chemokinrezeptor

CD:

„Cluster of differentiation“

CIAS:

„Cold induced autoinflammatory syndrome“

CINCA:

„Chronic infantile neurological cutaneous articular syndrome“

CMV:

Zytomegalievirus

CXCR:

CXC-Chemokinrezeptor

DAMPs:

„Damage-associated molecular patterns“

DNA:

Desoxyribonukleinsäure

EBV:

Epstein-Barr-Virus

FOXP3:

„Forkhead box proteins“

HLA:

Humanes Leukozytenantigen

HMGB:

„High mobility group box 1 protein“

HPF:

Hereditäre periodische Fiebersyndrome

HSP:

„Heat shock protein“

IFN:

Interferon

IkB:

IκB-Kinase

IKK:

IkappaB-Kinase-Komplex

IL:

Interleukin

ILAR:

„International League of Associations for Rheumatology“

IP:

„Interferon-inducible protein“

IPAF:

„ICE-Protease aktivierender Faktor“

IRF-1:

„Interferon regulatory factor 1“

JIA:

Juvenile idiopathische Arthritis

LPS:

Lipopolysaccharide

MIF:

„Macrophage migration inhibiting factor“

MRP:

„Myeloid related proteins“

MTX:

Methotrexat

NAIP:

Neuronaler Apoptose-inhibierender Faktor

NALP:

„NACHT-, LRR-, and PYD-containing“

NEMO:

„NF-kB essential modulator“

NF:

„Nuclear factor“

NFAT:

„Nuclear factor of activated T-cells“

NFκB:

„Nuclear factor kappaB“

NK-Zellen:

Natürliche Killerzellen

NLR:

„NACHT and leucine-rich repeat“

NOD:

„Nucleotide oligomerization domain“

NOMID:

„Neonatal syndrome of multisystem inflammation“

PAMPs:

„Pathogen associated molecular patterns“

PB:

Peripheres Blut

PBMC:

„Peripheral blood mononuclear cell“

PD-1:

„Programmed death-1“

PRR:

„Pattern recognition receptors“

PTPN:

„Protein tyrosine phosphatase, non-receptor“

RA:

Rheumatoide Arthritis

RAGE:

„Receptor for advanced glycation end products“

RF:

Rheumafaktor

RNA:

Ribonukleinsäure

SF:

Synovialflüssigkeit

SLE:

Systemischer Lupus erythematosus

SNPs:

„Single nucleotide polymorphisms“

SOCS:

„Suppressor of cytokine signaling“

STAT:

„Signal transducers and activator of transcription“

Teff:

T-Effektorzelle

TGF:

„Transforming growth factor“

Th:

T-Helferzelle

TLR:

„Toll-like receptor“

TNF:

Tumornekrosefaktor

TNFR:

TNF-Rezeptor

Treg:

Regulatorische T-Zelle

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  1. Zentrum für Kinder- und Jugendmedizin, Helios Klinikum Krefeld, Akademisches Lehrkrankenhaus der Heinrich-Heine-Universität Düsseldorf, Krefeld, Lutherplatz 40, 47805, Krefeld, Deutschland

    T. Niehues

  2. Klinik für Kinder-Hämatologie, -Onkologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland

    O. Feyen & T. Telieps

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  1. T. Niehues
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Niehues, T., Feyen, O. & Telieps, T. Vorstellungen zur Pathogenese der juvenilen idiopathischen Arthritis. Z. Rheumatol. 67, 111–120 (2008). https://doi.org/10.1007/s00393-008-0276-7

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