TY  - JOUR
A1  - Lenders, Malte
A1  - Hennermann, Julia B.
A1  - Kurschat, Christine
A1  - Rolfs, Arndt
A1  - Canaan-Kühl, Sima
A1  - Sommer, Claudia
A1  - Üçeyler, Nurcan
A1  - Kampmann, Christoph
A1  - Karabul, Nesrin
A1  - Giese, Anne-Katrin
A1  - Duning, Thomas
A1  - Stypmann, Jörg
A1  - Krämer, Johannes
A1  - Weidemann, Frank
A1  - Brand, Stefan-Martin
A1  - Wanner, Christoph
A1  - Brand, Eva
T1  - Multicenter Female Fabry Study (MFFS) - clinical survey on current treatment of females with Fabry disease
JF  - Orphanet Journal of Rare Diseases
N2  - Background
The aim of the present study was to assess manifestations of and applied treatment concepts for females with Fabry disease (FD) according to the current European Fabry Guidelines.

Methods
Between 10/2008 and 12/2014, data from the most recent visit of 261 adult female FD patients from six German Fabry centers were retrospectively analyzed. Clinical presentation and laboratory data, including plasma lyso-Gb3 levels were assessed.

Results
Fifty-five percent of females were on enzyme replacement therapy (ERT), according to recent European FD guidelines. Thirty-three percent of females were untreated although criteria for ERT initiation were fulfilled. In general, the presence of left ventricular hypertrophy (LVH) seemed to impact more on ERT initiation than impaired renal function. In ERT-naïve females RAAS blockers were more often prescribed if LVH was present rather than albuminuria. Affected females with missense mutations showed a similar disease burden compared to females with nonsense mutations. Elevated plasma lyso-Gb3 levels in ERT-naïve females seem to be a marker of disease burden, since patients showed comparable incidences of organ manifestations even if they were ~8 years younger than females with normal lyso-Gb3 levels.

Conclusion
The treatment of the majority of females with FD in Germany is in line with the current European FD guidelines. However, a relevant number of females remain untreated despite organ involvement, necessitating a careful reevaluation of these females.
KW  - Fabry disease
KW  - females
KW  - lyso-Gb3
KW  - enzyme replacement therapy
KW  - guidelines
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166543
VL  - 11
IS  - 88
ER  - 
TY  - JOUR
A1  - Lenz, Dominic
A1  - Pahl, Jens
A1  - Hauck, Fabian
A1  - Alameer, Seham
A1  - Balasubramanian, Meena
A1  - Baric, Ivo
A1  - Boy, Nikolas
A1  - Church, Joseph A.
A1  - Crushell, Ellen
A1  - Dick, Anke
A1  - Distelmaier, Felix
A1  - Gujar, Jidnyasa
A1  - Indolfi, Giuseppe
A1  - Lurz, Eberhard
A1  - Peters, Bianca
A1  - Schwerd, Tobias
A1  - Serranti, Daniele
A1  - Kölker, Stefan
A1  - Klein, Christoph
A1  - Hoffmann, Georg F.
A1  - Prokisch, Holger
A1  - Greil, Johann
A1  - Cerwenka, Adelheid
A1  - Giese, Thomas
A1  - Staufner, Christian
T1  - NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency
JF  - Journal of Clinical Immunology
N2  - Purpose
Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system.

Methods
Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system.

Results
Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell–intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia.

Conclusion
In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity.
KW  - NBAS
KW  - inborn error of immunity
KW  - NK cell deficiency
KW  - B cell deficiency
KW  - vesicle trafficking
KW  - familial hemophagocytic lymphohistiocytosis
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308362
SN  - 0271-9142
SN  - 1573-2592
VL  - 41
IS  - 8
ER  -