Faranaz Atschekzei, Germany
Hannover Medical School (MHH) Clinic for immunology and RheumatologyPresenter of 1 Presentation
A NOVEL CARMIL2 MUTATION RESULTING IN COMBINED IMMUNODEFICIENCY MANIFESTING WITH DERMATITIS, FUNGAL AND VIRAL SKIN INFECTIONS AS WELL AS SELECTIVE ANTIBODY DEFICIENCY
Abstract
Background and Aims
CIDs are caused by defects in T cell development and activation as well as compromised B cell activation with or without impaired B cell development. Phenotypes of CIDs are diverse, including infection, malignancy, allergy, autoimmunity and auto-inflammation. In order to identify the genetic basis of PID patients, we screened a panel of PID related genes by targeted next-generation sequencing.
Methods
By targeted NGS we identified a novel CARMIL2 mutation. Expression of CARMIL2 at protein level was characterized by flow cytometry and Western blot analysis. Functional analyzes were performed using flow cytometry.
Results
We report a novel homozygous splice site mutation in CARMIL2 gene in 3 affected individuals from a consanguineous family that presented with selective antibody deficiency, psoriasis, molluscum contagiosum as well as warts.
CARMIL2 expression was absent in naïve CD4+ T cells of all patients. Absolute numbers of CD4+ T cells and the proportion of CD4+ naïve T cells were increased, while percentages of CD4+ T memory and CD4+ T follicular-like T cells were reduced. The phosphorylation of NFκB subunit p65 in CD4+ T cells was abolished indicating the contribution of CARMIL2 in activation of NF-κB signaling.
Conclusions
These cases underline the role of CARMIL2 in immunity and suggest that CARMIL2 mutations should be considered in patients with disseminated and/or persistent warts. Differences in clinical and immunological phenotypes among our patients highlight the variable clinical presentations of CARMIL2-deficiency and suggest the pathogenic relevance of additional genetic and/or epigenetic modifying factors.