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Background and Aims

We studied the duration and consecutiveness of remission or lupus low disease activity state (LLDAS) throughout 52 weeks of therapy in relation to health-related quality of life (HRQoL) in systemic lupus erythematosus.

Methods

We analysed data from the BLISS-52 and BLISS-76 trials (N=1684). Remission/LLDAS required clinical (c)SLEDAI-2K=0/SLEDAI-2K≤4, PhGA<0.5/≤1 (0–3), and prednisone≤5/≤7.5 mg/day, respectively. HRQoL was measured using SF-36 physical/mental component summary (PCS/MCS) and EQ-5D-3L. Minimal clinically important difference (MCID) at week 52 was defined as PCS/MCS=2.5 and EQ-5D-3L=0.040. Quantile regression analysis was performed. Adjustments for patient characteristics, including organ damage, were incorporated.

Results

The minimum cumulative attainment of remission to achieve a benefit in PCS≥MCID at week 52 was four visits (β=0.63), while 7 visits were required for MCS differences ≥MCID (β=0.37). Correspondingly, 9 visits in LLDAS were required for achieving differences ≥MCID in both PCS (b=0.28) and MCS (β=0.29). Four consecutive visits in remission were required for PCS≥MCID (b=0.70), whereas six visits were required for MCS≥MCID (b=0.46). Sustained LLDAS for nine consecutive visits was needed for PCS/MCS≥MCID (b=0.31 for both). For EQ-5D-3L≥MCID to be reached, a cumulative total of seven visits in remission (b=0.006) or eight visits in LLDAS (b=0.005) was required, while if sustained, remission for six visits (b=0.008) or LLDAS for seven visits (b=0.006) was sufficient.

Conclusions

Longer time in remission was required to achieve clinically important differences in mental versus physical aspects of HRQoL, and longer time in LLDAS versus remission was required for multiple HRQoL aspects. Shorter time was required if the state was sustained.

Background and Aims

Neuropsychiatric systemic lupus erythematosus (NPSLE) refers to the collection of syndromes, ranging from psychosis to memory problems, which target the brain of 40-90% of subjects with lupus. Crucially, DNRAbs are lupus antibodies that bind DNA and cross-react with the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor. There is now compelling evidence for the pathogenic role of DNRAbs in NPSLE suggesting that these antibodies can cause memory dysfunction.

Methods

We have studied a mouse model of NPSLE in which animals carry DNRAbs, which enter the brain after a temporary disruption of the blood-brain barrier. We call this model "DNRAb+ mice" and they show spatial impairment that we measure with the object-place memory (OPM) task. DNRAb+ and DNRAb– (control) mice were implanted with tetrode arrays targeting the CA1 region of the hippocampus, which is a crucial brain substrate for spatial encoding. In vivo electrophysiology recordings were conducted during the OPM task to study place cells as well as power spectral densities of network oscillations.

Results

We found abnormal place cell properties in the DNRAb+ mice, such as expanded place field size, reduced stability, and lower spatial information when compared to DNRAb– mice. Moreover, we found significantly altered co-modulation of theta-gamma oscillations when the mice examined objects moved to novel locations.

Conclusions

Our behavioral and electrophysiological studies reveal disruptions in healthy place cell dynamics and oscillatory patterns by DNRAbs that may explain the abnormalities in spatial encoding that occur in NPSLE. Our data offer a substrate for brain-based biomarkers aimed at alleviating NPSLE-related cognitive impairment.

Background and Aims

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with significant morbidity and mortality. Approximately 15-20% of SLE patients develop disease before their 16^th birthday and are diagnosed with juvenile-onset SLE (JSLE). Neuropsychiatric (NP) involvement is a severe complication, encompassing neurological and psychiatric manifestations.

This study aimed to investigate the prevalence, demographic characteristics, and clinical features of NP disease in JSLE patients enrolled in the UK JSLE Cohort Study. Furthermore, associations between NP involvement and other clinical and/or laboratory features, as well correlation with disease severity and outcomes were investigated.

Methods

Demographic, clinical and laboratory features of NP-SLE of a large national cohort of JSLE were collected and compared to patients in the same cohort without NP manifestations.

Results

A total of 428 JSLE patients were included in this study, 25% of who exhibited NP features, half of them at first visit. Most common neurological symptoms among NP-JSLE patients included headaches (78.5%), mood disorders (48.6%), cognitive impairment (42%), anxiety (23.3%), seizures (19.6%), movement disorders (17.7%), and cerebrovascular disease (14.9%). Peripheral nervous system involvement was recorded in 7% of NP-SLE patients. NP-JSLE patients more frequently exhibited thrombocytopenia (<100 x 10⁹/L) (p=0.04), higher C-reactive protein levels (p=0.01), higher global pBILAG score at first visit (p<0.001), and higher SLICC damage index score at first (p=0.02) and last visit (p<0.001) when compared to JLSE patients without NP involvement.

Conclusions

A significant proportion of JSLE patients experience NP involvement (25%). Juvenile-onset NP-SLE most commonly affects the CNS and is associated with increased overall disease activity and damage.