Inhibitor-Immunology-Study

Summary

The development of inhibitors in haemophilia B is one of the most important complications of replacement therapy, affecting mortality and morbidity. Inhibitor development is based on complex immunological factors, and to date, only little is known about its underlying mechanisms. Here, we present first results of the haemophilia B group of our Inhibitor-Immunology study.

Patients, methods So far we have analysed 15 patients with haemophilia B. Four of them developed a high titre inhibitor; the remaining 11 had no inhibitor. We evaluated 9 SNPs in 8 genes (CD40, CTLA-4, IL-1β, IL-10, TLR2, TLR4, TLR9, TNF-α). We compared the distribution of these alleles between inhibitor and non-inhibitor haemophilia B patients and between haemophilia B patients and a normal male control population. HLA typing was performed in all patients.

Results, discussion There appears to be a trend towards a skewed distribution of TLR 9, IL-10 and CTLA4 alleles in haemophilia B patients. Due to the limited number these differences are, however, not statistically significant.The t-test of all patients with inhibitor versus without inhibitor was significant for HLA-A*03 and DPB1*0401 and borderline for DRB1*0201.

Zusammenfassung

Die Hemmkörperentwicklung der Hämophilie B ist eine der wichtigsten Komplikationen der Gerinnungsfaktor-Ersatztherapie, welche Mor- talität und Morbidität beeinflusst. Die Inhibitorentwicklung stellt ein komplexes immunologisches Geschehen dar, über deren Mechanismen nur wenig bekannt ist. Wir präsentieren die ersten Daten aus der Hämophilie B Gruppe der Inhibitor-Immunologie-Studie.

Patienten, Methoden Bisher haben wir 15 Patienten mit Hämophilie B analysiert. Vier der 15 haben einen hochtitrigen Hemmkörper, die übrigen 11 hatten keinen. Wir untersuchten neun SNPs in acht Genen (CD40, CTLA-4, IL-1β, IL-10, TLR2, TLR4, TLR9, TNF-α). Wir verglichen die Verteilung der Allele zwischen Hemmkörper- und Nicht-Hemmkörper-Patienten und zwischen Hämophilie B-Patient und einem männlichen Normalkollektiv. Außerdem führten wir eine HLA-Typisierung durch.

Ergebnisse, Diskussion Wir fanden einen Trend in der Allelverteilung von TLR 9, IL-10 und CTLA-4, der aufgrund der geringen Probenzahl nicht signifikant war. Der t-Test im Vergleich aller Patienten mit und ohne Hemmkörper war signifikant für HLA-A*03 und DPB1*0401 und grenzwertig für HLADRB1*0201.

Keywords

Haemophilia B - inhibitor - SNPs - HLA

Schlüsselwörter

Hämophilie B - Inhibitor - SNPs - HLA

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