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Background and Aims

Membranous glomerulonephritis (MG) causes about 25% of nephrotic syndromes in the adult. Etiology is autoimmune and it is due to the deposit of anti-phospholipase A2 receptor (Anti-PLA2R) immune complexes in the glomerular basement membrane. Anti-PLA2R is highly specific for primary membranous glomerulonephritis (PMG).

The aim was to implement the Anti-PLA2R (ELISA) in our laboratory and study its correlation with PMG, being a request from the department of Nephrology, as our hospital hosts a reference center for transplants.

Methods

Values of Anti-PLA2R were determined in 40 patients by ELISA, using a commercialized kit (Anti-PLA2R ELISA (IgG), by EUROIMMUN, Germany). Patients’ age ranged from 18 to 80. 22 individuals with Systemic Lupus Erythematosus (SLE), Diabetes Mellitus or other autoimmune diseases, alongside 2 patients with known Anti-PLA2R positive PMG, formed the problem group. 20 of them had nephropathy or proteinuria. The other 16 were healthy controls or had no autoimmune disease.

Results

39 presented negative Anti-PLA2R levels, except for one with PMG, with similar levels to the previous ones (53.58 RU/ml) from an external laboratory. The second PMG patient had 8.84 RU/ml, lower than previous results, which could indicate a good control of the disease.

3 patients with MG and SLE had levels of <0.1 RU/ml, implying a secondary cause of the MG.

Conclusions

Anti-PLA2R detection by ELISA allows quantification, which is necessary for the long-term follow-up of PMG, as it correlates with clinical manifestations and biochemical data of the associated renal failure. It is also useful for the evaluation of transplanted patients with PMG.

Background and Aims

The costimulatory pathway ICOS/ICOS-L plays a key-role in cooperation between B and T lymphocytes and appears to be involved in SLE. The aim of this study was to evaluate the association between ICOS and ICOS-L plasma levels, their renal expression and presence and severity of Lupus Nephritis (LN).

Methods

Main clinical and laboratory parameters were compared among 67 SLE patients (52 with LN and 15 with rheumatological SLE) and 50 healthy controls (HCs). Plasma levels of ICOS/ICOS-L were assessed by ELISA and their renal expression by immunohistochemistry analysis.

Results

Plasma levels of ICOS and ICOS-L were significantly increased in SLE as compared with HCs (p<0.001) and were associated with disease duration (p=0.036 for ICOS and p<0.001 for ICOS-L), presence and severity of LN at diagnosis (p=0.017 and p=0.001 respectively), proteinuria (p=0.014 and p<0.001) and nephritic sediment (p=0.005 and p = 0.001). ICOS levels correlated with SLICC (p=0.027) and SLEDAI-2K (p=0.001) at diagnosis. At multivariate analysis only disease onset at younger age (p=0.018) and ICOS-L levels (p=0,047) were indipendently associated with LN. Immunohistochemistry analysis brought out a more intense ICOS-L tubular expression in proteinuric as compared with non-proteinuric LN (p<0,05), whereas glomerular expression was weak.

Conclusions

ICOS and ICOS-L plasma levels were increased in SLE and identified a subset of patients with long-lasting disease and severe LN at presentation. A more intense tubular expression of ICOS-L was present in proteinuric forms of LN. These elements suggest that ICOS/ICOS-L pathway is involved in pathogenesis of LN and is promising as a biomarker and therapeutic target.

Background and Aims

Primary Membranous Nephropathy (MN) is a rare autoimmune renal disease associated with autoantibodies to PLA2R1 (70%), THSD7A (3%) or NELL1 (15%). A Chinese study showed an association between exposure to high levels of PM_2.5 and an increased risk of MN. The role of Th17 has been demonstrated in the pathogenesis of primary nephrotic syndrome in children, asthma or allergic contact dermatitis. Interaction with the environment seems to be important for the pathophysiology of MN but the link with cytokine profile has never been demonstrated.

We aim to correlate the cytokine profile of MN patients with environmental data.

Methods

Patients completed a questionnaire about their lifestyle habits. Environmental data was assessed by a geographer. Concentration of cytokines in the serum after nonspecific stimulation of T and NK cells with immune ligands was measured using Th1/Th2/Th9/Th17 18-Plex ProcartaPlex Panel (ThermoFisher Scientific).

Results

Fifty-seven patients with active MN and 27 healthy donors were included. MN patients had higher rates of IL-17A and IL-6 (p=0.036 and p=0.003, respectively), and deficiency of IL-10, IFN-γ and IL-12p70 (p=0.053, p=0.002 and p<0.0001, respectively), suggesting activation of Th17 pathway and a deficiency of Th1 and Treg pathways.

Patients with high level of IL-17A lived mostly in urban areas (82% vs 56%, p=0.033), worked in an office (46% vs 12%, p=0.006), were atopic (64% vs 38%, p=0.058) and had their first symptoms in spring (p=0.056). They had more venous thromboembolic events (p=0.032) and relapses (p=0.012).

Conclusions

MN patients have Th17-mediated inflammation related to an urban environment and atopic profile that probably induces immunization.