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Immungenetik—

HLA-Assoziation, molekulare Gouvernanten und „verwandte“ Krankheiten

Immunogenetics—HLA-association, molecular chaperones and “related” diseases

  • BEITRAG ZUM SCHWERPUNKTTHEMA
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Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Zusammenfassung

Seit langem ist die Assoziation der rheumatoiden Arthritis (RA) mit dem HLA-Komplex bekannt. Doch was bedeutet dies eigentlich? Es werden verschiedene Möglichkeiten einer immunologischen Interpretation in Erinnerung gerufen und eine neuere Variante vorgestellt. Hierbei handelt es sich um die Interaktion zwischen Komplexen aus Antigen und molekularen Chaperonen der HSP70-Familie einerseits und HLA-DR-β-Ketten andererseits, speziell der DRB1*0401-β-Kette, die die meisten RA-Patienten unserer Region tragen. Dieser Mechanismus könnte *0401+ Personen Vorteile bei der Infektabwehr, aber eine höhere Anfälligkeit für Autoimmunerkrankungen bringen. Chaperonmaschinen sind im Gelenk von Patienten mit rheumatoider Arthritis hoch reguliert. Was tun sie dort? Da ihre Anzahl und Vielfalt groß ist, bestehen viele Möglichkeiten, die von Antigenpräsentation bis zu Immunregulation reichen. Neben dem HLA-Komplex spielt der „genetische Hintergrund“ für die Entwicklung einer Autoimmunerkrankung eine wichtige Rolle. Dies lässt sich in Familien von Patienten mit RA oder Sklerodermie zeigen, in denen ein hoher Anteil der erstgradig Verwandten ebenfalls an einer „verwandten“ Krankheit leidet.

Summary

The association of rheumatoid arthritis (RA) with the HLA complex has been well established since 1978. But what does that mean? After reminding the reader of some existing immunological interpretations, a more recent variant is introduced. Antigens and molecular chaperones of the HSP70 family form complexes, which interact with HLA-DR β-chains, especially of the DRB1*0401 genotype, which is the most common among patients with RA in our region. This mechanism might bring *0401+ persons an advantage in defence against microorganisms, but a disadvantage concerning autoimmunity. Chaperone machines are upregulated in synovial tissue of RA patients. As their number and variety is huge in humans, there exist many possibilities for function, reaching from antigen presentation to immune regulation. In addition to the HLA complex, the “genetic background” plays an important role for the development of an autoimmune disease. This is demonstrated in families of patients with RA or scleroderma, where a high percentage of first degree relatives suffer from a “related” disease.

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  1. Klinische Forschergruppe für Rheumatologie, Universitätsklinikum Freiburg, Zentrale Klinische Forschung, Breisacher Str. 66, 79106, Freiburg, Germany

    I. Melchers

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Melchers, I. Immungenetik—. Z. Rheumatol. 64, 402–407 (2005). https://doi.org/10.1007/s00393-005-0768-7

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  • DOI: https://doi.org/10.1007/s00393-005-0768-7

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