The first national survey in Israel, performed in 2002, identified 39 SCID patients, of whom 20 (51%) were T-B- SCID phenotype and 8 (20%) were T-B+ SCID phenotype.27 Nine years later, 14 new cases (T-B- SCID = 6 and Omenn syndrome = were reported, and consanguinity was reported in 50% of the affected families.28 Interestingly, eight of the patients who had Omenn phenotype Afatinib research buy presented with normal numbers of lymphocytes and Inhibitors,research,lifescience,medical could therefore have

been misdiagnosed if absolute lymphocyte count-based methodology for the diagnosis of SCID had been used. Since the most frequent type of SCID genotype in Israel is the autosomal-recessive T-B- SCID, undetectable B cells in NBS is also very informative Inhibitors,research,lifescience,medical for the diagnosis of SCID and can immediately point to the specific abnormal gene (RAGs). This can be easily done simultaneously with TREC detection using quantification of KREC copies. The latter is used for the detection of newly produced bone marrow cells, making it a very sensitive and accurate way to estimate B lymphocytes. We recently assessed TREC and KREC counts to determine their ability to identify patients with combined T and

B cell immunodeficiency in Israel.29 Seven Israeli children who had been born between 2010 and Inhibitors,research,lifescience,medical 2011 and later diagnosed as having SCID were studied. TRECs and KRECs in their peripheral blood upon diagnosis and those in their neonatal Guthrie cards were analyzed using the accepted RTqPCR. The first features suggestive of SCID were presented at a mean age of 3.1 ± 2.4 months in all patients, but the diagnosis was not made until 4.1 ± 2.9 months later. Their TRECs were undetectable Inhibitors,research,lifescience,medical or significantly low during their clinical diagnosis and in their originally stored Guthrie cards, irrespective of the amount of their circulating T cells. KRECs were undetectable in the SCID patients who displayed B cell lymphopenia in addition to T cell lymphopenia. These results indicate that the quantification of TRECs Inhibitors,research,lifescience,medical is a sensitive and specific screening test for SCID and that the additional

quantification of KRECs can screen for B cell lymphopenia. It is quite logical to assume that several more children were not diagnosed; we estimate that Idoxuridine every year about seven to eight new cases of SCID are born. Thus the true incidence is about 1/20–25,000 (annual birth number in Israel is around 170,000). In conclusion, measurement of TREC content has become the best non-invasive clinical and research tool to investigate thymic activity. It allows the identification of recent thymic emigrants in peripheral blood and detection of T cell production by the thymus. It has recently been implemented in several states in the USA as a test to screen neonates for SCID, serving as the most sensitive and specific assay in such a devastating disease.