Lessons learned from the diagnostic work-up of a patient with the bare lymphocyte syndrome type II.

A patient presented severe combined immunodeficiency (SCID)-like symptoms. The presence of a substantial number of CD4+ T-cells in the peripheral blood was not explained by maternal engraftment. Genetic analysis revealed a novel RFXANK mutation, c.232C > T, resulting in a stop codon, with consequently defective transcription of MHC class II resulting in bare lymphocyte syndrome (BLS) type II. The initial unawareness of complete absence of MHC class II expression and normal T-cell receptor excision circles (TREC)-levels delayed the final diagnosis. After identification of the genetic defect the patient was scheduled for hematopoietic stem cell transplantation (HSCT). Here, we present and discuss the diagnostic and therapeutic approach of a novel case of BLS type II in relation to T-cell development.

Prenatal administration of multipotent adult progenitor cells modulates the systemic and cerebral immune response in an ovine model of chorioamnionitis.

Systemic and cerebral inflammation following antenatal infection (e.g. chorioamnionitis) and dysregulation of the blood brain barrier (BBB) are major risk factors for abnormal neonatal brain development. Administration of multipotent adult progenitor cells (MAPCs) represents an interesting pharmacological strategy as modulator of the peripheral and cerebral immune response and protector of BBB integrity. We studied the immunomodulatory and protective cerebrovascular potential of prenatally administered MAPCs in a preclinical ovine model for antenatal inflammation. Ovine fetuses were intra-amniotically (i.a.) exposed to lipopolysaccharide (LPS) or saline at gestational day 125, followed by the intravenous administration of 1*107 MAPCs or saline at gestational day 127. Circulating inflammation markers were measured. Fetal brains were examined immuno-histochemically post-mortem at gestational day 132. Fetal plasma IL-6 levels were elevated significantly 24 h after LPS administration. In utero systemic MAPC treatment after LPS exposure increased Annexin A1 (ANXA1) expression in the cerebrovascular endothelium, indicating enforcement of BBB integrity, and increased the number of leukocytes at brain barriers throughout the brain. Further characterisation of brain barrier-associated leukocytes showed that monocyte/choroid plexus macrophage (IBA-1+/CD206+) and neutrophil (MPO+) populations predominantly contributed to the LPS-MAPC-induced increase of CD45+cells. In the choroid plexus, the percentage of leukocytes expressing the proresolving mediator ANXA1 tended to be decreased after LPS-induced antenatal inflammation, an effect reversed by systemic MAPC treatment. Accordingly, expression levels of ANXA1 per leukocyte were decreased after LPS and restored after subsequent MAPC treatment. Increased expression of ANXA1 by the cerebrovasculature and immune cells at brain barriers following MAPC treatment in an infectious setting indicate a MAPC driven early defence mechanism to protect the neonatal brain against infection-driven inflammation and potential additional pro-inflammatory insults in the neonatal period.

Testing for IgA anti-tissue transglutaminase in routine clinical practice: Requesting behaviour in relation to prevalence of positive results.

OBJECTIVE: Due to the high awareness of coeliac disease and improvement of serological tests, the number of requested laboratory tests has increased substantially over the years. In the current study we have evaluated the requesting behaviour of distinct clinical disciplines in relation to the prevalence of positive results and in the context of existing guidelines. METHODS: Data were retrospectively extracted from the laboratory information system over a time-span of 5 years in a tertiary hospital and compared with the situation in a secondary hospital. RESULTS: Data reveal that for initial testing (n=18,183) the percentage positive results for IgA anti-TTG is <2%. Paediatricians have a slightly higher percentage of seropositive results (2.4-4.0%). Early confirmation (<2 months) of positive results by IgA anti-endomysium antibodies in an independent sample is only performed in a minority of paediatric patients. The majority of positive patients, however, have follow-up measurements (<14 months) in order to examine compliance to a gluten-free diet. Interestingly, initial requests for paediatric patients reveal an equal distribution between boys and girls, while in adult patients there is a two times preponderance of requests in female patients, similar to the female/male ratio in patients with positive results, being either paediatric or adult patients. CONCLUSION: Although laboratory testing for coeliac disease may be primarily used to exclude the disease, it is evident that the percentage positive results for IgA anti-TTG is extremely low. This may indicate that the clinical manifestations that warrant testing, should be further specified in order to increase the pre-test probability. As the specific serology is important to bypass a biopsy in the diagnosis of coeliac disease according to the paediatric guideline, the confirmation in an independent sample needs to get more attention.