The clinical utility of molecular diagnostic testing for primary immune deficiency disorders: a case based review

Primary immune deficiency disorders (PIDs) are a group of diseases associated with a genetic predisposition to recurrent infections, malignancy, autoimmunity and allergy. The molecular basis of many of these disorders has been identified in the last two decades. Most are inherited as single gene defects. Identifying the underlying genetic defect plays a critical role in patient management including diagnosis, family studies, prognostic information, prenatal diagnosis and is useful in defining new diseases. In this review we outline the clinical utility of molecular testing for these disorders using clinical cases referred to Auckland Hospital. It is written from the perspective of a laboratory offering a wide range of tests for a small developed country

Update on the hyper immunoglobulin M syndromes

The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination (CSR), with or without defects of somatic hypermutation (SHM). They can be classified as defects of signalling through CD40 causing both a humoral immunodeficiency and a susceptibility to opportunistic infections, or intrinsic defects in B cells of the mechanism of CSR resulting in a pure humoral immunodeficiency. A HIGM picture can also be seen as part of generalized defects of DNA repair and in antibody deficiency syndromes, such as common variable immunodeficiency. CD40 signalling defects may require corrective therapy with bone marrow transplantation. Gene therapy, a potential curative approach in the future, currently remains a distant prospect. Those with a defective CSR mechanism generally do well on immunologoblulin replacement therapy. Complications may include autoimmunity, lymphoid hyperplasia and, in some cases, a predisposition to lymphoid malignancy

Multidisciplinary investigations of the diets of two post-medieval populations from London using stable isotopes and microdebris analysis

This paper presents the first multi-tissue study of diet in post-medieval London using both the stable light isotope analysis of carbon and nitrogen and analysis of microdebris in dental calculus. Dietary intake was explored over short and long timescales. Bulk bone collagen was analysed from humans from the Queen’s Chapel of the Savoy (QCS) (n = 66) and the St Barnabas/St Mary Abbots (SB) (n = 25). Incremental dentine analysis was performed on the second molar of individual QCS1123 to explore childhood dietary intake. Bulk hair samples (n = 4) were sampled from adults from QCS, and dental calculus was analysed from four other individuals using microscopy. In addition, bone collagen from a total of 46 animals from QCS (n = 11) and the additional site of Prescot Street (n = 35) was analysed, providing the first animal dietary baseline for post-medieval London. Overall, isotopic results suggest a largely C3-based terrestrial diet for both populations, with the exception of QCS1123 who exhibited values consistent with the consumption of C4 food sources throughout childhood and adulthood. The differences exhibited in δ15Ncoll across both populations likely reflect variations in diet due to social class and occupation, with individuals from SB likely representing wealthier individuals consuming larger quantities of animal and marine fish protein. Microdebris analysis results were limited but indicate the consumption of domestic cereals. This paper demonstrates the utility of a multidisciplinary approach to investigate diet across long and short timescales to further our understanding of variations in social status and mobility