Inhibitor-Immunology-Study

Summary

The development of inhibitors is one of the most important complications of replacement therapy in haemophilia, affecting mortality and morbidity. Inhibitor development is based on complex immunological factors. Cytokines and their receptors, T-cell receptors, and the Major Histocompatibility Complex may play important roles in the development of inhibitors. Earlier studies showed non significant associations between HLA class and inhibitor development. Later studies found an increased risk of inhibitor development if there was a combination between certain factor VIII mutations and HLA antigens. We performed HLA typing in 50 patients with haemophilia A in an effort to find associations with inhibitor development. Results: 25 patients had developed an inhibitor (11 low titre, 14 high titre), and 25 never had. In logistic regression analysis, HLA-A 34, DRB1 0405, DRB1 1301 seemed to be involved in inhibitor development and HLA-A 30, B 13, B15, B 57, Cw 12, DQB1 0303, DPB1 0201 protection against inhibitor development. In our patients, the HLA-associations with inhibitor development were different from those in previous publications.

Zusammenfassung

Die Inhibitorentstehung ist eine der wichtigsten Komplikationen der Substitutionsbehandlung der Hämophilie, die Mortalität und Morbitität beeinflusst. Die Inhibitorentstehung ist ein komplexes immunologische Geschehen, in das Zytokine, deren Rezeptoren, T-Zell-Rezeptoren und der Major-Histokompatibilitätskomplex eine entscheidende Rolle spielen. In frühen Studien konnte kein signifikanter Zusammenhang zwischen Inhibitorentwicklung und HLA-Typ gezeigt werden. Spätere Studien fanden ein höheres Risiko einen Hemmkörper zu entwickeln, wenn eine Kombination bestimmter Mutationen und HLA-Antigenen auftrat. Wir führten eine HLA-Typisierung von 50 Patienten mit Hämophilie A durch, um eine Assoziation zur Inhibitorenstehung zu finden. Ergebnis: 25 Patienten entwickelten einen Inhibitor (11 niedrig titrig, 14 hoch titrig), 25 nicht. In der logistischen Regression scheinen HLA-A 34, DRB1 0405, DRB1 1301 in die Inhibitorentstehung involviert zu sein, während HLA-A 30, B 13, B15, B 57, Cw 12, DQB1 0303, DPB1 0201 protektiv wirken. Unsere Ergebnisse unterscheiden sich von den Daten anderer Arbeitsgruppen.

Keywords

Haemophilia - inhibitor - HLA

Schlüsselwörter

Hämophilie - Inhibitor - HLA

• Literatur

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