Skip to main content
SpringerLink
Log in

Immunologie der entzündlichen Systemerkrankungen

Immunology of systemic inflammatory diseases

  • Leitthema
  • Published:
Der Orthopäde Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Entzündlich-rheumatische Erkrankungen sind in aller Regel Systemerkrankungen, die auf Fehlfunktionen des Immunsystems zurückzuführen sind.

Methode

Relevante pathophysiologische Vorgänge im Immunsystem werden anhand von Laborergebnissen, Autoantikörpertests und v. a. neuer Medikamente dargestellt. Darüber hinaus wird ein immunologisch fokussierter Überblick über klinisch relevante Ansätze gegeben.

Ergebnisse

Die pathophysiologische Rolle sowohl von T‑ und B‑Lymphozyten als auch von Autoantikörpern zeigt, dass es sich bei Erkrankungen wie der rheumatoiden Arthritis (RA), den Kollagenosen und Vaskulitiden um Autoimmunerkrankungen handelt. Während der Tumornekrosefaktor offenbar bei vielen Vorgängen eine relevante Rolle spielt, differenzieren andere Zytokine zwischen RA (Interleukin 6, IL-6) und Spondylarthritiden (IL-17, IL-23). Bei Kristallarthritiden ist hingegen IL-1 entscheidend.

Abstract

Background

Inflammatory rheumatic diseases are generally systemic diseases resulting from immune system dysfunction.

Methods

Relevant pathophysiological processes in the immune system are discussed using laboratory results and autoantibody tests, as well as in terms of new drugs in particular. Furthermore, an immunologically focused overview of clinically relevant approaches is presented.

Results

The pathophysiological role of both T and B lymphocytes as well as that of autoantibodies demonstrates that diseases such as rheumatoid arthritis (RA), connective tissue diseases, and vasculitides are autoimmune diseases. While tumor necrosis factor is apparently involved in many entities, other cytokines differentiate between RA (interleukin-6, IL-6) and spondylarthritides (IL-17, IL-23). In contrast, in crystal arthritides, IL-1 appears essential.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abbreviations

ATG:

Antithymozytenglobulin

bDMARDS:

„Biological disease-modifying anti-rheumatic drugs“

CRP:

C-reaktives Protein

GPA:

Granulomatose mit Polyangiitis (Wegener)

IFN:

Interferon

Ig:

Immunglobulin

IL:

Interleukin

MPA:

Mikrokopische Polyangiitis

MTX:

Methotrexat

NK-Zellen:

Natürliche Killerzellen

PsA:

Psoriasisarthritis

RA:

Rheumatoide Arthritis

SLE:

Systemischer Lupus erythematodes

SSc:

Systemische Sklerose

TNF:

Tumornekrosefaktor

Literatur

  1. Aringer M, Hedrich C, Tausche AK (2016) Inflammasome and gout. Z Rheumatol 75:537–541

    Article  CAS  PubMed  Google Scholar 

  2. Schlesinger N, Mysler E, Lin HY, De MM, Rovensky J, Arulmani U et al (2011) Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study. Ann Rheum Dis 70:1264–1271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Klareskog L, Stolt P, Lundberg K, Kallberg H, Bengtsson C, Grunewald J et al (2006) A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 54:38–46

    Article  CAS  PubMed  Google Scholar 

  4. Schellekens GA, Visser H, de Jong BA, van den Hoogen FH, Hazes JM, Breedveld FC et al (2000) The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43:155–163

    Article  CAS  PubMed  Google Scholar 

  5. Arend WP, Firestein GS (2012) Pre-rheumatoid arthritis: predisposition and transition to clinical synovitis. Nat Rev Rheumatol 8:573–586

    Article  CAS  PubMed  Google Scholar 

  6. Smolen JS, Kalden JR, Scott DL, Rozman B, Kvien TK, Larsen A et al (1999) Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group. Lancet 353:259–266

    Article  CAS  PubMed  Google Scholar 

  7. Weinblatt ME, Schiff M, Valente R, van der Heijde D, Citera G, Zhao C et al (2013) Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum 65:28–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Emery P, Fleischmann R, Filipowicz-Sosnowska A, Schechtman J, Szczepanski L, Kavanaugh A et al (2006) The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 54:1390–1400

    Article  CAS  PubMed  Google Scholar 

  9. Smolen JS, Landewe R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M et al (2017) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 76:960–977

    Article  PubMed  Google Scholar 

  10. Burmester GR, McInnes IB, Kremer J, Miranda P, Korkosz M, Vencovsky J et al (2017) A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis. Ann Rheum Dis 76:1020–1030

    Article  CAS  PubMed  Google Scholar 

  11. Aringer M (2017) Janus kinase inhibitors clear to land: Janus kinase inhibitors in RA. Rheumatology (Oxford). https://doi.org/10.1093/rheumatology/kex217. (Jun 13 Epub)

    Article  Google Scholar 

  12. Choy E, Rose-John S (2017) Interleukin-6 as a multifunctional regulator: inflammation, immune response, and fibrosis. J Scleroderma Relaat Disord 2:1–5

    Article  Google Scholar 

  13. Pavelka K, Kivitz A, Dokoupilova E, Blanco R, Maradiaga M, Tahir H et al (2017) Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3. Arthritis Res Ther 19:285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Nash P, Kirkham B, Okada M, Rahman P, Combe B, Burmester GR et al (2017) Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet 389:2317–2327

    Article  CAS  PubMed  Google Scholar 

  15. Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P et al (2017) Anifrolumab, an Anti-Interferon-alpha Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol 69:376–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE et al (2011) Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 377:721–731

    Article  CAS  PubMed  Google Scholar 

  17. Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A, Kohler S et al (2009) Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood 113:214–223

    Article  CAS  PubMed  Google Scholar 

  18. Khanna D, Denton CP, Jahreis A, van Laar JM, Frech TM, Anderson ME et al (2016) Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial. Lancet 387:2630–2640

    Article  CAS  PubMed  Google Scholar 

  19. Lundberg IE, Miller FW, Tjarnlund A, Bottai M (2016) Diagnosis and classification of idiopathic inflammatory myopathies. J Intern Med 280:39–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dalakas MC (2011) Review: an update on inflammatory and autoimmune myopathies. Neuropathol Appl Neurobiol 37:226–242

    Article  CAS  PubMed  Google Scholar 

  21. Tjarnlund A, Tang Q, Wick C, Dastmalchi M, Mann H, Tomasova SJ et al (2018) Abatacept in the treatment of adult dermatomyositis and polymyositis: a randomised, phase IIb treatment delayed-start trial. Ann Rheum Dis 77:55–62

    Article  CAS  PubMed  Google Scholar 

  22. Unger L, Kampf S, Luthke K, Aringer M (2014) Rituximab therapy in patients with refractory dermatomyositis or polymyositis: differential effects in a real-life population. Rheumatology (Oxford) 53:1630–1638

    Article  CAS  Google Scholar 

  23. Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA et al (2010) Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 363:211–220

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Deutschland

    M. Aringer

  2. Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, München, Deutschland

    H. Schulze-Koops

Authors
  1. M. Aringer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Schulze-Koops
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Aringer.

Ethics declarations

Interessenkonflikt

M. Aringer weist auf folgende Beziehungen hin: Advisory Boards und/oder Vorträge für AbbVie, Astra Zeneca, BMS, Chugai, GSK, Hexal Sandoz, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi. Klinische Prüfungen für Studien von AbbVie, Astra Zeneca, Boehringer Ingelheim, Novartis, Pfizer, Roche. H. Schulze-Koops weist auf folgende Beziehungen hin: Advisory Boards und/oder Vorträge für AbbVie, Actelion, AstraZeneca, Biogen International, Boehringer Ingelheim, BMS, Celgene, Chugai, GSK, Hexal Sandoz, Hospira, Janssen-Cilag, Lilly, MSD, Medac, Merck, Mundipharma, Novartis, Pfizer, Roche, Sanofi, UCB. Klinische Prüfungen für Studien von AbbVie, AstraZeneca, Baxter, Biotest, BMS, Boehringer Ingelheim, Celgene, Chugai, CSL Behring, GSK, Hexal Sandoz, Hospira, Janssen Cilag, Lilly, MSD, Medac, Mundipharma, Novartis, Octapharma, Pfizer, Roche, UCB.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aringer, M., Schulze-Koops, H. Immunologie der entzündlichen Systemerkrankungen. Orthopäde 47, 891–898 (2018). https://doi.org/10.1007/s00132-018-3647-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00132-018-3647-z

Schlüsselwörter

Keywords

Search

Navigation