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A previously unknown B-cell deficiency was identified in a teenager with the aid of next generation sequencing and detailed functional analyses.

(Vienna 19th 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 the research group of Kaan Boztug at CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences in collaboration with the Medical University of Vienna and the St. Anna Children’s Hospital. A previously unknown B-cell deficiency was identified in the teenager with the aid of next generation sequencing and detailed functional analyses. 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 medial 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 state-of-the art genomic 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 Kaan Boztug and his colleague Elisabeth Förster-Waldl, who works as a 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 successful molecular identification of the deficiency. From early childhood onwards, the patient had suffered repeatedly from severe autoimmunity of the kidneys, lymph nodes and connective tissues. The now 13-year-old boy had previously been treated using global immunosuppression with corticosteroids for extended periods of time. On the background of the molecular data, this treatment may now be modified. Says Förster-Waldl: "Only when you know the mechanism, an individually tailored therapy can be appropriately used or developed."

Data from the international immunodeficiency registries 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 a systematic collection of data has only been initiated two years ago.

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 technologies. Most immunodeficiencies are classified as so-called "rare diseases". Kaan Boztug: "However, the sum total of all these defects cannot be categorised as rare. For us they represent model diseases which enable us to understand the composition of the immune system at a molecular level and to develop personalized treatment approaches”.

The world-wide so-termed "Rare Disease Day" will take place on 28th February 2013 ( 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.