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Objective: End points currently used in lupus nephritis (LN) clinical trials lack uniformity and questionably reflect long‐term kidney survival. This study was undertaken to identify short‐term end points that predict long‐term kidney outcomes for use in clinical trials. Methods: A database of 944 patients with LN was assembled from 3 clinical trials and 12 longitudinal cohorts. Variables from the first 12 months of treatment after diagnosis of active LN (prediction period) were assessed as potential predictors of long‐term outcomes in a 36‐month follow‐up period. The long‐term outcomes examined were new or progressive chronic kidney disease (CKD), severe kidney injury (SKI), and the need for permanent renal replacement therapy (RRT). To predict the risk for each outcome, hazard index tools (HITs) were derived using multivariable analysis with Cox proportional hazards regression. Results: Among 550 eligible subjects, 54 CKD, 55 SKI, and 22 RRT events occurred. Variables in the final CKD HIT were prediction‐period CKD status, 12‐month proteinuria, and 12‐month serum creatinine level. The SKI HIT variables included prediction‐period CKD status, International Society of Nephrology (ISN)/Renal Pathology Society (RPS) class, 12‐month proteinuria, 12‐month serum creatinine level, race, and an interaction between ISN/RPS class and 12‐month proteinuria. The RRT HIT included age at diagnosis, 12‐month proteinuria, and 12‐month serum creatinine level. Each HIT validated well internally (c‐indices 0.84–0.92) and in an independent LN cohort (c‐indices 0.89–0.92). Conclusion: HITs, derived from short‐term kidney responses to treatment, correlate with long‐term kidney outcomes, and now must be validated as surrogate end points for LN clinical trials. [ABSTRACT FROM AUTHOR]

Objective To assess circulating follicular helper T (Tfh)-like CD4+ T cells in patients with systemic lupus erythematosus (SLE) and determine their relationship to disease activity. Methods Blood samples from patients with SLE, as well as blood samples from patients with Behçet's disease (BD) and healthy individuals as controls, were analyzed. In all samples, circulating Tfh-like cells were enumerated by flow cytometry, using, as markers, expression of CXCR5, inducible T cell costimulator (ICOS), and programmed death 1 (PD-1) protein, as well as secretion of interleukin-21 (IL-21). The frequency of circulating Tfh-like cells was compared to that of circulating plasmablasts (CD19+IgD−CD38+). In addition, the possible association of circulating Tfh-like cells with the SLE Disease Activity Index (SLEDAI) was evaluated. Results The subset of circulating Tfh-like T cells, identified as CXCR5highICOShighPD-1high, was expanded in the blood of SLE patients compared to controls. Circulating Tfh-like cells were found to produce IL-21 and had lower expression of CCR7 as compared to that in circulating CXCR5high central memory T cells, thereby enabling their distinction. Expression of PD-1, but not ICOS or CXCR5, was significantly elevated in circulating Tfh-like cells from SLE patients compared to controls. PD-1 expression among CXCR5high circulating Tfh-like cells correlated with the SLEDAI, frequency of circulating plasmablasts, and anti-double-stranded DNA antibody positivity, but not with disease duration or past organ injury; rather, this cell profile appeared to be a reflection of current active disease. Conclusion Circulating Tfh-like cells are associated with disease activity in SLE, suggesting that their presence indicates abnormal homeostasis of T cell-B cell collaboration, with a causal relationship that is central to disease pathogenesis. These findings also suggest that circulating Tfh-like cells provide a surrogate for aberrant germinal center activity in SLE, and that their PD-1 expression offers a tool for measuring disease activity and monitoring the response to therapies. [ABSTRACT FROM AUTHOR]