Follicular B helper T (Tfh) cells support high affinity and long-term antibody responses. Here we found that within circulating CXCR5⁺ CD4⁺ T cells in humans and mice, the CCR7(lo)PD-1(hi) subset has a partial Tfh effector phenotype, whereas CCR7(hi)PD-1(lo) cells have a resting phenotype. The circulating CCR7(lo)PD-1(hi) subset was indicative of active Tfh differentiation in lymphoid organs and correlated with clinical indices in autoimmune diseases. Thus the CCR7(lo)PD-1(hi) subset provides a biomarker to monitor protective antibody responses during infection or vaccination and pathogenic antibody responses in autoimmune diseases. Differentiation of both CCR7(hi)PD-1(lo) and CCR7(lo)PD-1(hi) subsets required ICOS and BCL6, but not SAP, suggesting that circulating CXCR5⁺ helper T cells are primarily generated before germinal centers. Upon antigen reencounter, CCR7(lo)PD-1(hi) CXCR5⁺ precursors rapidly differentiate into mature Tfh cells to promote antibody responses. Therefore, circulating CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells are generated during active Tfh differentiation and represent a new mechanism of immunological early memory.

We analyzed data from the Australia and New Zealand Dialysis and Transplant Registry for 1 October 2003 to 31 December 2008 with the aim of describing the nature of peritonitis, therapies, and outcomes in patients on peritoneal dialysis (PD) in Australia. At least 1 episode of PD was observed in 6639 patients. The overall peritonitis rate was 0.60 episodes per patient-year (95% confidence interval: 0.59 to 0.62 episodes), with 6229 peritonitis episodes occurring in 3136 patients. Of those episodes, 13% were culture-negative, and 11% were polymicrobial. Gram-positive organisms were isolated in 53.4% of single-organism peritonitis episodes, and gram-negative organisms, in 23.6%. Mycobacterial and fungal peritonitis episodes were rare. Initial antibiotic therapy for most peritonitis episodes used 2 agents (most commonly vancomycin and an aminoglycoside); in 77.2% of episodes, therapy was subsequently changed to a single agent. Tenckhoff catheter removal was required in 20.4% of cases at a median of 6 days, and catheter removal was more common in fungal, mycobacterial, and anaerobic infections, with a median time to removal of 4 - 5 days. Peritonitis was the cause of death in 2.6% of patients. Transfer to hemodialysis and hospitalization were frequent outcomes of peritonitis. There was no relationship between center size and peritonitis rate. The peritonitis rate in Australia between 2003 and 2008 was higher than that reported in many other countries, with a particularly higher rate of gram-negative peritonitis.

Steroid-sensitive nephrotic syndrome (SSNS) accounts for .80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68310 26 (Fisher exact test). Two of these SNPs-the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1-were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and #589 controls; P=1.42310 217). In the rare variant gene set-based analysis, the best signal was found in PLCG2 (P=7.825310 25). In conclusion, this exome array study identified HLA-DQA1 and PLCG2 missense coding variants as candidate loci for SSNS. The finding of a MHC class II locus underlying SSNS risk suggests a major role for immune response in the pathogenesis of SSNS.

Toll-like receptor 9 (TLR9) enhances proinflammatory responses, but whether it can act in a regulatory capacity remains to be established. In experimental murine AKI induced by cisplatin, Tlr9