Welcome to the 2021 LUPUS CORA Meeting Program Scheduling

Background and Aims

B-cell killing by rituximab depends on antibody-dependent cellular cytotoxicity (ADCC). A genetic polymorphism in the Fc Gamma Receptor (FcγR) with an increased affinity for IgG1 could influence response. The study objectives were to assess the effect of the full range of FcγR variants on depletion, clinical response and functional effect on NK-cell-mediated killing.

Methods

A prospective longitudinal study was conducted in a UK rituximab registry. Major clinical response (MCR) was defined as improvement of active BILAG-2004 domains to grade C/better at 6 months. Partial Clinical response (PCR) allowed 1 persistent B. B-cell depletion was evaluated by highly-sensitive flow cytometry. Qualitative and quantitative polymorphisms for five major FcγRs were measured using multiplex ligation-dependent probe amplification. NK-cell degranulation (CD107a) in the presence of rituximab-coated Raji cells were assessed using flow cytometry.

Results

262 patients were studied. In cycle 1 rituximab, 177/262 (67.6%) achieved BILAG response [MCR=34.4%; PCR=33.2%]. No clinical/serological feature consistently predicted depletion and response. At the genotypic level, complete depletion was associated with carriage of FCGR3A-158V allele, OR 2.95 (95% CI 1.16-7.51) and FCGR2C-ORF allele 3.3 (1.12-9.72). By integrating copy number and functional SNP analysis, MCR was associated with higher number copies of FCGR3A-158V allele, 1.64 (1.12-2.41) and FCGR2C-ORF allele 1.93 (1.09-3.40). For FCGR3A, degranulation activity was higher in the V allele carriers vs FF; p=0.024.

Conclusions

ADCC-enhancing FcγRIIIa and FcγRIIc variants were associated with complete B-cell depletion and MCR in SLE. This was supported by functional data on NK-cell-mediated cytotoxicity. These results may guide stratification and development of more effective B-cell targeted strategies.

Background and Aims

The frequency of relapses in lupus nephritis (LN) is variable and it depends on the definition used.

Objetives

To analyze the frequency and number of relapsing LN

To compare SLE patients with and without relapses in LN and to evaluate associated factors with relapses

Methods

A retrospective, observational and analytical study that included adult LN patients. Relapsing LN was defined as an increase of kidney function, proteinuria and/ or altered urinary sediment that required an increase in the dose or initiation of corticosteroid/ immunosuppressant. The number of relapses/ patient and factors associated with relapsing LN were analyzed.

Results

One thousand four hundred and ninety-four patients were analyzed: 183 out of 635 LN (28.8%) patients had renal relapse (91% women, median age of 36.2 years (IQR 29.9- 46.1), median age at SLE diagnosis of 24.5 years (IQR 18.2- 31.5).

One- hundred and twenty-nine patients had only one renal relapse and 33 cases presented two relapses.

In the multivariate analysis, time of evolution of SLE (OR 1.006, IC 95% [1.004-1.008], p <0.0001), proteinuria >0.5 gr/day in the last visit (OR 3.987, IC 95% [2.545-6.297], p <0.0001) and hematuria in the last visit (OR 1.743, IC 95% [1.058-2.947], p 0.032) were independent risk factors for relapses in LN.

Conclusions

Relapsing LN occurred in almost a third of our patients. The time of evolution SLE and the persistence of an active urine sediment were independent risk factors for relapses in LN. This finding in the urine of our patients is a tool for decision making.

Background and Aims

Renal transplantation is the therapy of choice in patients with end stage lupus nephritis (LN).

To analyze the characteristics and outcomes of renal transplantation in LN patients.

Methods

Retrospective, descriptive study in SLE patients (ACR 82-97) who received a renal transplant (RTx). Demographic variables, donor characteristics, post-transplant immunosuppressant treatments, causes of graft loss, deaths and their causes and patient and graft survival were analyzed.

Results

Forty-one patients (90.2% women) were analyzed. The median time from dialysis to transplant was 99.1 months (IQR 59.9-131.7). A 87.8% of the cases received cadaveric renal graft. The most used immunosuppressant treatment was mycophenolate mofetil + tacrolimus + corticoids in 56.1% of the patients. A total of 12/41 (29.2%) of patients experienced graft rejection or failure. The main causes of graft loss were diagnosed as chronic allograft nephropathy (n=8), BK virus infection (n=1), focal and segmental glomerulosclerosis (n=1), renal artery thrombosis (n=1) and acute allograft rejection (n=1). In only two patients (4.8%) the graft extraction was performed and no patients the transplant was performed in a second time. A 4.8% of the cases presented relapsing NL in the graft but without loss it. Eight patients (19.5%) died and the main causes of death were: infectious (n=5), cardiovascular (n=2) and lymphoma (n=1). Patient survival at one, five and ten years was 100%, 87,8% y 80,4%, respectively and the median graft survival was 73 months (IQR: 41.7-122.9).

Conclusions

Patient survival was favorable. One third of the patients with Lupus and kidney transplantation suffered graft loss and 19% died during follow-up