CeMM Research Institute for Molecular Medicine and University Dep. of Paediatrics & Adolescent Medicine

(Vienna 21st February 2013) Severe autoimmunity in childhood can be an indication of a primary immunodeficiency (PID) – this has now been demonstrated in a 13-year-old patient by a research group from the MedUni Vienna belonging to the CeMM Research Center for Molecular Medicine of the AAS and the St. Anna Children’s Hospital. A previously unknown B-cell defect was identified in the teenager with the aid of so-called "next generation sequencing", with which genetic mutations in the genetic material can be detected within a few days. The study has been published in "Blood".  

 "Our discovery created a sense of relief in the family as they now know at last what is wrong with the boy," says Kaan Boztug, who holds a dual appointment as a doctor at the University Department of Paediatrics and Adolescent Medicine treating seriously ill children, and as a researcher at CeMM, searching for the molecular causes of diseases of the immune system using the most modern genetic technologies. In this specific case a defect in the PRKCD gene was discovered. This causes a malfunction in the regulation of the B lymphocytes which are regarded as "antibody factories". Severe autoimmunity develops as a consequence.   According to Boztug and Elisabeth Förster-Waldl, paediatrician and immunologist at the University Department of Paediatrics and Adolescent Medicine of the MedUni Vienna, not only diagnostic, but also therapeutic, consequences can be derived from the recently successful molecular identification of the deficiency. From early childhood the patient had suffered periodically from severe autoimmunity of the kidneys, lymph nodes and connective tissues. The now 13-year-old had previously been globally immunosuppressed with cortisone for long periods but now the target of the therapy can be precisely isolated. Says Förster-Waldl: "Only when you know the mechanism, an individually tailored therapy can be appropriately used or developed."   Data from the Anglo-American world assume that the prevalence of a clinically relevant immunodeficiency that can sometimes involve life-threatening consequences for those affected lies at between 1:1200 and 1:2000. Such figures can only be estimated for Austria as the  systematic collection of data has only been taking place for the last two years. At present around 30 to 40 percent of these deficiencies remain without a precise diagnosis according to Förster-Waldl. This could now change with the aid of the latest diagnostic  processes including "next generation sequencing". Most immunodeficiencies are classified as  so-called "rare diseases". Kaan Boztug: "However, the sum total of all these defects cannot be  categorised as rare."  Worldwide "Rare Disease Day" is taking place on 28th February 2013 (http://www.rarediseaseday.org/country/at/austria). This day was created in order to draw  increased attention to these disease groups so as to be able to offer patients like the one  described better diagnosis possibilities and the prospect of effective therapies. In total there are  about 8,000 rare diseases. Eight out of ten of these diseases appear in childhood.  Service: Blood "B cell deficiency and severe autoimmunity caused by deficiency of protein kinase C delta." E. Salzer, E. Santos-Valente, S. Klaver, S. A. Ban, W. Emminger, N. Prengemann, W. Garnarcz,  L. Müllauer, R. Kain, H. Boztug, A. Heitger, K. Arbeiter, F. Eitelberger, M. Seidel, W. Holter, A.  Pollak, W. Pickl, E. Förster-Waldl and K. Boztug. doi. 10.1182/blood-2012-10-460741. CeMM (Research Center for Molecular Medicine of the Austrian Academy of Sciences) – summary  profile  The CeMM is an international, independent and interdisciplinary research organisation for molecular medicine.  "Improving clinical practice through clinical research" – the CeMM focuses on medical need and integrates  fundamental research as well as clinical expertise to develop innovative diagnostic and therapeutic approaches. Its  areas of expertise include cancer, inflammatory conditions and immunodeficiencies. Information: www.cemm.oeaw.ac.at.  Medical University of Vienna – summary profileThe Medical University of Vienna (MedUni Vienna) is one of Europe’s medical training and research facilities with the  greatest history and tradition. Counting almost 7,500 students, it is today the largest medical training facility in the  German-speaking region. With its 31 university departments, 12 medical-theoretical centres and numerous highly  specialised laboratories, it also ranks amongst the most significant cutting-edge research institutions in Europe in the  biomedical sector. Over 48,000 square metres of space have been dedicated to clinical research at the facility.