The functional interaction of BAFF and APRIL with TNF receptor superfamily members BAFFR, TACI and BCMA is crucial for development and maintenance of humoral immunity in mice and humans. Using a candidate gene approach, we identified homozygous and heterozygous mutations in TNFRSF13B, encoding TACI, in 13 individuals with common variable immunodeficiency. Homozygosity with respect to mutations causing the amino acid substitutions S144X and C104R abrogated APRIL binding and resulted in loss of TACI function, as evidenced by impaired proliferative response to IgM-APRIL costimulation and defective class switch recombination induced by IL-10 and APRIL or BAFF. Family members heterozygous with respect to the C104R mutation and individuals with sporadic common variable immunodeficiency who were heterozygous with respect to the amino acid substitutions A181E, S194X and R202H had humoral immunodeficiency. Although signs of autoimmunity and lymphoproliferation are evident, the human phenotype differs from that of the Tnfrsf13b-/- mouse model.

Objectives Across Europe, almost a third of individuals infected with HIV do not enter health care until late in the course of their infection. Surveillance to identify the extent to which late presentation occurs remains inadequate across Europe and is further complicated by the lack of a common clinical definition of late presentation. The objective of this article is to present a consensus definition of late presentation of HIV infection. Methods Over the past year, two initiatives have moved towards a harmonized definition. In spring 2009, they joined efforts to identify a common definition of what is meant by a ‘late‐presenting’ patient. Results Two definitions were agreed upon, as follows. Late presentation: persons presenting for care with a CD4 count below 350 cells/μL or presenting with an AIDS‐defining event, regardless of the CD4 cell count. Presentation with advanced HIV disease: persons presenting for care with a CD4 count below 200 cells/μL or presenting with an AIDS‐defining event, regardless of the CD4 cell count. Conclusion The European Late Presenter Consensus working group believe it would be beneficial if all national health agencies, institutions, and researchers were able to implement this definition (either on its own or alongside their own preferred definition) when reporting surveillance or research data relating to late presentation of HIV infection.

Objectives: Antioxidant defense status was investigated in HIV-infected patients by measuring serum selenium, erythrocyte glutathione peroxidase (GSH-Px) activity, plasma thiol (-SH) and glutathione (GSH) concentrations along with the assessment of the clinical stage and surrogate markers of HIV-disease. Design, setting and subjects: Serum selenium levels were determined cross-sectionally in 104 sequentially selected HIV-infected patients (83 outpatients and 21 patients with ongoing AIDS de®ning events). The patients were classi®ed into three stages of the disease, I, II and III according to the 1993 Centers For Disease Control (CDC) classi®cation system for HIV-infection. GSH-Px activities, plasma SH and plasma GSH concentrations were determined in a subset of 24 patients at stage I and 12 patients at stage III with an active AIDS-de®ning disease. Results: Mean serum selenium levels were lower in CDC stage II (68.7 AE 20.9 mg/l; P`0.01; n 34) and stage III (51.4 AE 14.7 mg/l; P`0.01; n 37) HIV-infected patients than in healthy subjects (89.2 AE 20.9 mg/l; n 72) and stage I patients (82.3 AE 20.5; mg/l; n 33). Serum selenium levels were positively correlated with CD4-count (r 0.42; P`0.001; n 104) and inversely with levels of soluble tumor necrosis factor receptors type II (r 7 0.58; P`0.01; n 35), neopterin (r 70.5; P`0.001; n 80) and b2-microglobulin (r 70.4; P`0.001; n 94). Hepatitis C virus (HCV) and HIV-coinfected patients at CDC stages I and II showed markedly lower selenium concentrations compared to HIV-infected patients without concomitant HCVinfection. Serum selenium and GSH-Px activity in hospitalized AIDS patients was signi®cantly lower as compared to asymptomatic patients and healthy subjects, whereas plasma SH and GSH concentrations were lower in both, asymptomatic -and AIDS-patients, than in the controls. Conclusion:The results show that stages I±III of HIV-disease are characterized by signi®cant impairments of antioxidative defenses provided by selenium, GSH-Px, SH-groups and GSH. Sponsorship:

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Echocardiographic screening detected PH in a substantial proportion of HIV-positive patients. Female gender, a history of injecting drug use and HPC origin were associated with a higher prevalence of HIV-associated PH. The relevance and long-term outcome of these findings need to be validated in follow-up studies, which are ongoing.