Translational mini-review series on immunodeficiency: molecular defects in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a primary immunodeficiency that typically affects adults and is characterized by abnormalities of quantative and qualitative humoral function that are heterogeneous in their immunological profile and clinical manifestations. The recent identification of four monogenic defects that result in the CVID phenotype also demonstrates that the genetic basis of CVID is highly variable. Mutations in the genes encoding the tumour necrosis factor (TNF) superfamily receptors transmembrane activator and calcium-modulating ligand interactor (TACI) and B cell activation factor of the TNF family receptor (BAFF-R), CD19 and the co-stimulatory molecule inducible co-stimulator molecule (ICOS) all lead to CVID and illustrate the complex interplay required to co-ordinate an effective humoral immune response. The molecular mechanisms leading to the immune defect are still not understood clearly and particularly in the case of TACI, where a number of heterozygous mutations have been found in affected individuals, the molecular pathogenesis of disease requires further elucidation. Together these defects account for perhaps 10-15% of all cases of CVID and it is highly likely that further genetic defects will be identified.

Global distribution of TEM-1 and ROB-1 beta-lactamases in Haemophilus influenzae.

OBJECTIVES: To determine the global distribution of TEM-1 and ROB-1 beta-lactamases in Haemophilus influenzae isolated from patients with community-acquired respiratory tract infection during the first 4 years of the PROTEKT study (1999-2003). To investigate the activities of commonly used antibiotics against these isolates. METHODS: For 14 870 H. influenzae, MIC testing was performed using NCCLS broth microdilution methodology. For 2225 beta-lactamase-positive (BLP) H. influenzae, TEM-1 and ROB-1 genes were detected using a Taqman PCR method. RESULTS: beta-Lactamase positivity was 15.0% overall but varied greatly by country (<5% in several countries to 67.9% in Taiwan). Prevalences of TEM-1 and ROB-1 BLP H. influenzae were 93.7% and 4.6%, respectively, however almost all ROB-1 isolates were found in Canada, the USA and Mexico. ROB-1 isolates (n = 102) were less susceptible against cefaclor (29.4% versus 87.6%) and cefprozil (42.2% versus 91.9%) than TEM-1 (n = 2085) isolates. Differences in susceptibility rates for chloramphenicol, co-trimoxazole and tetracycline were also found between the two groups. CONCLUSIONS: The ROB-1 beta-lactamase was found almost exclusively in North America and was more active against cefaclor and cefprozil than the TEM-1 beta-lactamase.