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.

This large-scale epidemiological survey provides an estimate of the burden of rheumatic diseases in China.

BackgroundSystemic lupus erythematosus (SLE) is associated with significant impairment of health-related quality of life (HR-QoL). Recently, meeting a definition of a lupus low disease activity state (LLDAS), analogous to low disease activity in rheumatoid arthritis, was preliminarily validated as associated with protection from damage accrual. The LLDAS definition has not been previously evaluated for association with patient-reported outcomes. The objective of this study was to determine whether LLDAS is associated with better HR-QoL, and examine predictors of HR-QoL, in a large multiethnic, multinational cohort of patients with SLE.MethodsHR-QoL was measured using the Medical Outcomes Study 36-item short form health survey (SF-36v2) in a prospective study of 1422 patients. Disease status was measured using the SLE disease activity index (SLEDAI-2 K), physician global assessment (PGA) and LLDAS.ResultsSignificant differences in SF-36 domain scores were found between patients stratified by ethnic group, education level and damage score, and with the presence of active musculoskeletal or cutaneous manifestations. In multiple linear regression analysis, Asian ethnicity (p < 0.001), a higher level of education (p < 0.001), younger age (p < 0.001) and shorter disease duration (p < 0.01) remained significantly associated with better physical component scores (PCS). Musculoskeletal disease activity (p < 0.001) was negatively associated with PCS, and cutaneous activity (p = 0.04) was negatively associated with mental component scores (MCS). Patients in LLDAS had better PCS (p < 0.001) and MCS (p < 0.001) scores and significantly better scores in multiple individual SF-36 domain scores. Disease damage was associated with worse PCS (p < 0.001), but not MCS scores.ConclusionsEthnicity, education, disease damage and specific organ involvement impacts HR-QoL in SLE. Attainment of LLDAS is associated with better HR-QoL.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1256-6) contains supplementary material, which is available to authorized users.

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BackgroundSystemic lupus erythematosus (SLE) is a chronic heterogeneous disease with considerable burden from disease activity and damage. A novel clinical treatment target in the form of the lupus low disease activity state (LLDAS) has been recently reported, with retrospective validation showing that time spent in LLDAS translates to reduced damage accrual. The objectives of this study were to describe the frequency and identify the predictors of attaining LLDAS in a large multinational cohort of patients with SLE.MethodsData were collected at the recruitment visit in patients with SLE enrolled in a longitudinal study in nine countries. Data were analysed cross-sectionally against the recently published definition of LLDAS, and the frequency and characteristics associated with presence of LLDAS were determined. Stepwise multivariable logistic regression was used to determine predictors of LLDAS.ResultsOf the 1846 patients assessed, criteria for LLDAS were met by 44 %. Patients with shorter disease duration were less likely to be in LLDAS (OR 0.31, 95 % CI 0.19–0.49, p < 0.001). Likewise, patients with a history of discoid rash (OR 0.66, 95 % CI 0.49–0.89, p = 0.006), renal disease (OR 0.60, 95 % CI 0.48–0.75, p < 0.001), elevated double stranded DNA (OR 0.65, 95 % CI 0.53–0.81, p < 0.001) or hypocomplementaemia (OR 0.52, 95 % CI 0.40–0.67, p < 0.001) were less likely to be in LLDAS. When countries were compared, higher national social wealth (OR 1.57, 95 % CI 1.25–1.98, p < 0.001) as measured by the gross domestic product per capita was positively associated with LLDAS, but ethnicity was not.ConclusionThe lupus low disease activity state is observed in less than half of patients with SLE at a single point in time. Disease duration and phenotype, and national social wealth, are predictive of LLDAS.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1163-2) contains supplementary material, which is available to authorized users.