Abstracts (complete list) - Wissenschaft Online

Markus Krumbholz, Hans Faber, Florian Steinmeyer, Lisa-Ann Hoffmann, Hannah
Pellkofer, Tania Kümpfel, Tobias Derfuß, Camelia Ionescu, Michaela Starck, Thomas
Giese, Gunther Hartmann, Christian Hafner, Reinhard Hohlfeld, Edgar Meinl
Type I interferon therapy increases systemic BAFF expression
Type I interferons (IFN-I) play a key role both in the physiological immune response
after e.g. viral infection and in autoimmune diseases like SLE. Besides effects on T cells,
effects on the B cell system are increasingly recognized. We asked whether IFN-I
regulate the BAFF/APRIL system, which is crucial for the normal B cell physiology, and
may also drive autoimmune diseases and malignancies.
We report that systemic BAFF expression was elevated in MS patients treated with IFN-
&beta, but not in untreated patients. BAFF transcription in vivo in monocytes and
granulocytes correlated with that of MxA, a typical IFN-&beta regulated gene. Further in
vitro analysis confirmed that IFN-&beta concentrations reached in vivo in treated MS
patients induce BAFF in these immune cell subsets and also in tissue resident cells
(fibroblasts and astrocytes). In contrast to BAFF, APRIL was only slightly induced by IFN-
&beta. The hybrid transcript TWE-PRIL was expressed several orders of magnitude
lower in vivo. The receptors BCMA, TACI, BARF-R were not regulated by IFN-&beta.
The systemic induction of BAFF by type I IFNs shed light on a mechanism for the
physiological interplay of innate and adaptive immunity at the level of B cells, on
complex immunomodulatory effects of IFN-&beta treatment in MS patients, on how type
I IFN therapy may lead to the known induction of autoantibodies or even clinical
autoimmunity as a side effect, and on how type I IFNs may aggrevate autoimmunity in
e.g. SLE.