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Zur Rolle von HLA-B27 in der Pathogenese und Diagnostik der axialen Spondyloarthritis

50 Jahre nach Entdeckung der starken genetischen Assoziation

The role of HLA-B27 in the pathogenesis and diagnosis of axial spondyloarthritis

50 years after discovery of the strong genetic association

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Zusammenfassung

Hintergrund

Die Assoziation des humanen Lymphozytenantigens B27 (HLA-B27) mit der ankylosierenden Spondylitis (AS), heute axiale Spondyloarthritis (axSpA), ist zuerst vor 50 Jahren beschrieben worden.

Ziel der Arbeit

Ziel ist es, einen Überblick über die dazu vorliegenden Erkenntnisse zu geben.

Material und Methoden

Es erfolgt ein narratives Review auf Basis der Erfahrung der Autoren.

Ergebnisse

HLA-B27 ist ein Mitglied der HLA-Klasse-I-Familie von Genen des Haupthistokompatibilitätskomplexes (MHC). Die Prävalenz von HLA-B27 in der mitteleuropäischen Bevölkerung liegt bei etwa 8 %, d. h. die überwiegende Mehrheit von HLA-B27+-Merkmalsträgern bleibt gesund. Die Häufigkeit von HLA-B27 weist ein Nord-Süd-Gefälle auf. HLA-B27 erklärt weniger als 30 % der genetischen Last der axSpA. Die Prävalenz der Erkrankung korreliert mit der Häufigkeit von HLA-B27 in der Bevölkerung, d. h. es gibt geografische Unterschiede. Etwa 60–90 % der axSpA-Patienten weltweit sind HLA-B27+. Durch Polymerasekettenreaktion (PCR) können ca. 200 Subtypen von HLA-B27 differenziert werden. In Thailand bzw. auf Sardinien wurden 2 Subtypen gefunden, die nicht mit axSpA assoziiert sind. Die physiologische Funktion von HLA-Klasse-I-Molekülen besteht darin, den Organismus gegen Mikroben zu verteidigen. Dabei werden dem Immunsystem mikrobiale Peptide präsentiert, die von CD8+-T-Zellen gezielt angegriffen werden können. Genpolymorphismen des Enzyms Aminopeptidase 1 (ERAP1), welches im endoplasmatischen Retikulum Peptide zurechtschneidet, sind nur mit HLA-B27+-Erkrankungen assoziiert.

Diskussion

Die Pathogenese der axSpA ist unklar, eine bedeutende Hypothese ist die des arthritogenen Peptids. Dabei geht man davon aus, dass potenziell pathogene Fremd- oder Selbstpeptide durch HLA-B27 präsentiert werden können. Nicht zuletzt spielt HLA-B27 auch eine wichtige Rolle bei Diagnosestellung, Klassifikation und Bestimmung des Schweregrads einer axSpA.

Abstract

Background

The association of the human lymphocyte antigen B27 (HLA-B27) with ankylosing spondylitis (AS), also now called axial spondylarthritis (axSpA), was first described 50 years ago.

Objective

This article gives an overview of the available knowledge on the topic.

Material and methods

This is a narrative review based on the experience of the authors.

Results

The HLA-B27 is a member of the HLA class I family of genes of the major histocompatibility complex (MHC). The prevalence of HLA-B27 in the central European population is approximately 8 %, i.e., the vast majority of carriers of HLA-B27+ remain healthy. The frequency of HLA-B27 shows a decline from north to south. The HLA-B27 explains only 30 % of the genetic burden of axSpA. The prevalence of the disease correlates with the frequency of HLA-B27 in the population, i.e., there are geographic differences. Approximately 60–90 % of patients with axSpA worldwide are HLA-B27+. Some 200 subtypes of HLA-B27 can be differentiated using the polymerase chain reaction (PCR). In Thailand and Sardinia two subtypes were found that are not associated with axSpA. The physiological function of HLA class I molecules is the defence of the organism against microbes. Microbial peptides are presented to the immune system, which can be specifically attacked by CD8+ T‑cells. Genetic polymorphisms of the enzyme endoplasmic reticulum aminopeptidase 1 (ERAP1), which breaks down peptides in the endoplasmic reticulum, are associated only with HLA-B27+ diseases.

Discussion

The pathogenesis of axSpA is unclear but a major hypothesis is that of the arthritogenic peptides. In this it is assumed that potentially pathogenic foreign or autologous peptides can be presented by HLA-B27. If nothing else, HLA-B27 plays an important role in the diagnosis, classification and determination of the severity of axSpA.

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Authors and Affiliations

  1. Rheumatologisches Versorgungszentrum Steglitz, Berlin, Deutschland

    Jürgen Braun

  2. Ruhr Universität Bochum, Bochum, Deutschland

    Jürgen Braun

  3. Klinikum Bielefeld, Universitätsklinikum OWL der Universität Bielefeld, Bielefeld, Deutschland

    Martin Rudwaleit

  4. Charité Universitätsmedizin Berlin, Berlin, Deutschland

    Joachim Sieper

  5. Berlin, Deutschland

    Jürgen Braun

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  1. Jürgen Braun
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Correspondence to Jürgen Braun.

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Ulf Müller-Ladner, Bad Nauheim

Uwe Lange, Bad Nauheim

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Der Verlag bleibt in Hinblick auf geografische Zuordnungen und Gebietsbezeichnungen in veröffentlichten Karten und Institutsadressen neutral.

Der vorliegende Artikel basiert auf einem englischsprachigen Artikel [89] und wurde speziell für die deutsche Rheumatologie und deren Rolle bei den entzündlichen Wirbelsäulenerkrankungen und des Einflusses von HLA-B27 bearbeitet.

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Braun, J., Rudwaleit, M. & Sieper, J. Zur Rolle von HLA-B27 in der Pathogenese und Diagnostik der axialen Spondyloarthritis. Z Rheumatol 83, 125–133 (2024). https://doi.org/10.1007/s00393-023-01460-0

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