Available via license: CC BY-NC 4.0
Content may be subject to copyright.
clinically. Histologic activity and damage were calculated using
National Institutes of Health activity and chronicity indices.
Lupus nephritis class transformation and changes in the degree
of immune complex deposition were determined. Descriptive
statistics and comparison tests were used before and after
induction treatment.
Results A total of 44 patients were identified. Complete clini-
cal response was achieved in 43% (19/44) after induction
and 69% (29/42) at one year. None of the complete res-
ponders after induction had histologic activity index of > 2
on repeat biopsy (figure 1). Activity index after induction in
complete responders (median 1, range 0-2) was lower than
in partial or non-responders (median 2, range 0-10) (p-value
< 0.005). Complete clinical response was associated with
transformation to a non-proliferative class in 79% (15/19)
and a reduction in immune complex deposition in 68% (13/
19) on repeat biopsy.
Conclusions Unlike adult-onset lupus nephritis, clinical and his-
tologic remission are more congruent after induction therapy
in childhood-onset disease. There was good correlation
between clinical response and activity index.
Lay Summary Lupus nephritis can cause kidney failure. The
need to balance risks and benefits of immunosuppression
requires stringent monitoring. In adults with lupus, available
diagnostics are insufficient to gauge response to initial ”induc-
tion”therapy and repeat biopsy studies are necessary to rigor-
ously test novel biomarkers. Here we show that repeat biopsy
in children performed 1/2 year into therapy correlates well
with clinical response, but there is a subset of children with
sub-clinical scarring that would be missed without repeat
biopsy - this subset may be at risk long-term for kidney
failure.
1109 VISUALIZING IN SITU IMMUNE PATHOGENIC
MECHANISMS IN HUMAN LUPUS NEPHRITIS
1
Marcus Clark*,
2
Madeleine Durkee,
1
Rebecca Abraham,
1
Gabriel Casella,
1
Junting Ai,
1
Deepjyoti Ghosh,
1
Thao Cao,
2
Maryellen Giger.
1
Department of Medicine, Section of
Rheumatology, Knapp Center for Lupus and Immunology research;
2
Department of
Radiology. University of Chicago, Chicago, IL 60637
10.1136/lupus-2022-lupus21century.74
For over 50 years, systemic lupus erythematosus (SLE) has
been thought to result from a break in systemic tolerance and
production of pathogenic autoreactive antibodies. In the kid-
ney, the manifestation of systemic autoimmunity is glomerulo-
nephritis (GN). However, tubulointerstitial inflammation
(TII)—and not GN—predicts progression to end stage renal
disease (ESRD). Lupus TII is associated with a local immune
response very different than the inflammation observed in glo-
meruli. These observations indicate that in situ immunity is a
central pathogenic mechanism of lupus nephritis. Recently, we
developed computational pipelines by training and implement-
ing several deep learning models to identify cells and cellular
spatial relationships in biopsies from lupus nephritis patients.
When applied to confocal micrographs of renal tissue, this
analytic approach revealed discrete in situ inflammatory states
in lupus nephritis which differed in cellular constituency, spa-
tial architecture and prognosis. These observations demonstrate
the utility of studying in situ immunity to both identify prog-
nostic groups and therapeutic targets. In follow up studies, we
are using high dimensional confocal microscopy to capture the
full complexity of lupus nephritis in situ immunity innate and
adaptive immunity in order to identify those immunological
pathways that lead to fibrosis and renal failure.
Funded by grants from the NIH Autoimmunity Centers of
Excellence (U19 AI082724) and Alliance for Lupus Research
Lupus Nephritis
1110 VOCLOSPORIN IS EFFECTIVE IN ACHIEVING
PROTEINURIA TREATMENT TARGETS IN LUPUS
NEPHRITIS DEFINED BY EULAR/ERA
RECOMMENDATIONS
1
Hans-Joachim Anders,
2
Ray Federico,
2
Simrat Randhawa,
2
Henry Leher,
2
Elmar Orujov.
1
Klinikum der Universität München, Munich, Germany;
2
Aurinia Pharmaceuticals Inc.,
Victoria, Canada
10.1136/lupus-2022-lupus21century.75
Background Pooled data from the Phase 2 AURA-LV and
Phase 3 AURORA 1 studies demonstrated that adding voclo-
sporin, a novel calcineurin inhibitor, to mycophenolate mofetil
Abstract 1108 Figure 1 Findings at first biopsy (baseline, at time of nephritis diagnosis) and repeat biopsy (5-7 months into therapy) stratified by
clinical response at time of repeat biopsy (CR, complete response; PR, partial response; NR, no response). Shown are medians (lines), means (large
circles), and ranges (activity index scored 0 to 24 and chronicity index scored 0 to 12 based on ISN/RPS schema).
Abstracts
Lupus Science & Medicine 2022;9(Suppl 3):A1–A112 A75
on January 4, 2023 by guest. Protected by copyright.http://lupus.bmj.com/Lupus Sci Med: first published as 10.1136/lupus-2022-lupus21century.75 on 14 December 2022. Downloaded from
(MMF) and low-dose steroids resulted in significantly higher
complete renal response rates at 24 weeks in AURA-LV
(32.6% vs 19.3%; odds ratio [OR] 2.03; p=0.045) and 52
weeks in AURORA 1 (40.8% vs 22.5%; OR 2.65; p<
0.0001) in patients with lupus nephritis.
The European League Against Rheumatism and European
Renal Association (EULAR/ERA) published updated treatment
recommendations for lupus nephritis with targeted reductions
in proteinuria over the course of the first year of therapeutic
intervention. Here we report on a post-hoc analysis of pooled
data from the similarly-designed 48-week AURA-LV and 52-
week AURORA 1 studies based on the recommended treat-
ment targets.
Methods AURA-LV and AURORA 1 enrolled patients with
biopsy-proven active lupus nephritis (Class III, IV, or V ± III/
IV) and proteinuria 1.5 mg/mg (2 mg/mg for Class V).
Pooled data included 268 patients in the voclosporin arm and
266 patients in the control arm; all patients received MMF
(target dose 2 g/day) and low-dose steroids (target dose 2.5
mg/day by week 16 according to protocol-defined steroid
taper). We assessed the following EULAR/ERA treatment tar-
gets: 25% reduction in urine protein creatinine ratio (UPCR)
at 3 months, 50% reduction in UPCR at 6 months, UPCR
£0.7 mg/mg at 12 months, and steroid dose £7.5 mg/day at
12 months.
Results After 3 months of treatment, 78.4% of patients in the
voclosporin group and 62.4% of patients in the control group
achieved 25% reduction in UPCR (odds ratio [OR] 2.25;
95% confidence interval [CI] 1.52, 3.33; p< 0.0001). The
percentage of patients achieving a reduction of 50% in
UPCR at 6 months was significantly greater in the voclosporin
arm (66.0% vs 47.0%, respectively; OR 2.24; CI 1.57, 3.21;
p< 0.0001). At 12 months, 52.6% and 33.1% of the voclo-
sporin and control arms, respectively, had achieved a UPCR
£0.7 mg/mg (OR 2.52; CI 1.75, 3.63; p< 0.0001). A total of
89.6% and 82.8% of patients in the voclosporin and control
arms, respectively, had reached the recommended steroid dose
of £7.5 mg/day at 12 months. The proportion of patients
achieving a UPCR £0.7 mg/mg and having a steroid dose
£7.5 mg/day at 12 months was 44.4% in the voclosporin arm
and 27.1% in the control arm (OR 2.42; CI 1.66, 3.53; p<
0.0001).
Conclusions The addition of voclosporin to a background regi-
men of MMF and low-dose steroids in patients with LN sig-
nificantly increased the likelihood of achieving the 3-, 6-, and
12-month UPCR targets of therapy recommended by EULAR/
ERA.
Lupus Nephritis
1111 TYPE I INTERFERON AND NEUTROPHIL TRANSCRIPTS IN
LUPUS NEPHRITIS RENAL BIOPSIES: CLINICAL AND
HISTOPATHOLOGICAL ASSOCIATIONS
1,2,3
Clio P Mavragani,
1
Kyriakos A Kirou,
4
Surya V Seshan,
1
Mary K Crow*.
1
Mary Kirkland
Center for Lupus Research, Hospital for Special Surgery and Weill Cornell Medical College,
NY, NY, 10021, USA;
2
Department of Physiology, School of Medicine, National and
Kapodistrian University of Athens, Athens, Greece
10.1136/lupus-2022-lupus21century.76
Objectives To investigate the expression of type I interferon
(IFN-I) and neutrophil transcripts in kidney tissue from
patients with distinct classes of lupus nephritis and their asso-
ciation with clinical and histopathological features.
Patients and Methods Quantitation of IFN-I and defensin-a3
transcripts was performed in kidney biopsies from 24 patients
with various classes of lupus nephritis (6 class III, 14 class IV,
4 class V) and 3 control samples by real-time PCR. Demo-
graphic characteristics, creatinine levels, and histopathological
characteristics, including activity and chronicity indices, pres-
ence of active glomerular lesions, and tubulointerstitial or vas-
cular involvement were analyzed.
Results IFNa2 and btranscripts were overexpressed in renal
tissues from patients with proliferative forms of lupus nephri-
tis (III/IV) compared to patients with membranous nephritis
and control kidneys. Such difference was not detected between
membranous nephritis and control biopsies. Defensin-a3 tran-
scripts, overexpressed in lupus nephritis biopsies –particularly
those with segmental necrotizing lesions - were correlated
with higher activity index (r=0.61, p=0.02). Patients with
proliferative lupus nephritis with impaired renal function, as
attested by elevated creatinine levels, displayed higher relative
expression of IFNa2 transcripts in renal tissues compared to
those with normal renal function (26.6 ±18.0 vs. 7.1 ±6.2,
p=0.013).
Conclusion IFN-I transcripts are produced locally in kidneys
from patients with the proliferative, but not membranous,
forms of lupus nephritis in association with impaired renal
function. Neutrophil transcript defensin-a3isapotential
biomarker for increased renal pathologic activity. These
findings provide insight into mechanisms of proliferative
lupus nephritis and could impact therapeutic decisions in
clinical practice.
1112 CHANGE IN URINARY BIOMARKERS AT THREE MONTHS
PREDICTS 1-YEAR TREATMENT RESPONSE OF LUPUS
NEPHRITISBETTER THAN PROTEINURIA
1
Andrea Fava*,
2
Laurence Magder,
1
Daniel W Goldman,
3
Jill Buyon,
4
Betty Diamond,
5
Joel Guthdridge,
5
Judith A James,
6
William Apruzzese,
1
Derek Fine,
1
Jose Monroy Trujillo,
1
Mohamed G Atta,
3
Peter Izmirly,
3
H Michael Belmont,
4
Anne Davidson,
7
Maria Dall’Era,
6
Deepak Rao,
4
Arnon Arazi,
8
Nir Hacohen,
6,8
Soumya Raychaudhuri, the Accelerating
Medicines Partnership in RA/SLE Network, and Michelle Petri
1
.
1
Johns Hopkins University,
USA;
2
University of Maryland, USA;
3
NYU Grossman School of Medicine, USA;
4
The
Feinstein Institutes for Medical Research, USA;
5
Oklahoma Medical Research Foundation,
USA;
6
Brigham and Women’s Hospital, USA;
7
University of California, San Francisco, USA;
8
Broad Institute, USA
10.1136/lupus-2022-lupus21century.77
Intro/Background A decline of urine protein-to-creatinine ratio
(UPCR) to < 0.5 is associated with better long-term preserva-
tion of kidney function in lupus nephritis (LN). UPCR < 0.5
defines complete response in guidelines and clinical trials
when achieved after 1 or 2 years. Biomarkers of early
response are needed to guide early treatment changes. We
studied longitudinal urine proteomic profiles in LN to identify
early predictors of proteinuric response.
Methods We quantified 1200 biomarkers (Kiloplex, RayBio-
tech) in urine samples collected on the day of (73%) or
within 3 weeks (27%) of kidney biopsy and week 12, 24, or
52 in LN patients (ISN class III, IV, V, or mixed) with protei-
nuria > 1 g/d. Response was defined at one year from renal
biopsy: Complete = UPCR <0.5, serum creatinine (sCr)
<125% of baseline, prednisone £10mg/d; Partial = UPCR <
50% from baseline but >0.5, sCr <125% of baseline, but
Abstracts
A76 Lupus Science & Medicine 2022;9(Suppl 3):A1–A112
on January 4, 2023 by guest. Protected by copyright.http://lupus.bmj.com/Lupus Sci Med: first published as 10.1136/lupus-2022-lupus21century.75 on 14 December 2022. Downloaded from
