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ObjectivesChronic renal impairment remains a feared complication of lupus nephritis (LN). The present work aimed at identifying mechanisms and markers of disease severity in renal tissue samples from patients with LN.MethodsWe performed high-throughput transcriptomic studies (Illumina HumanHT-12 v4 Expression BeadChip) on archived kidney biopsies from 32 patients with LN and eight controls (pretransplant donors). Histological staging (glomerular and tubular scores) and immunohistochemistry experiments were performed on the same and on a replication set of 37 LN kidney biopsy samples.ResultsA group of LN samples was identified by unsupervised clustering studies based on their gene expression features, that is, the overexpression of transcripts involved in antigen presentation, T and B cell activation. These samples were characterised by a significantly lower estimated glomerular filtration rate (eGFR) at the time of biopsy (T0) compared with the other systemic lupus erythematosus samples. Yet, apparent disease duration at T0, double-stranded DNA antibody titres at T0 and other relevant characteristics (serum C3, proteinuria, histological scores, numbers of previous flares) were not different between groups.Immunohistochemistry studies confirmed the association between interstitial infiltration by adaptive immune effectors and decreased renal function in the same and in a replication group of LN kidney biopsies. This was associated with transcriptomic, histological and immunohistochemical evidence of renal tubular cell involvement.ConclusionInterstitial infiltration of LN kidney biopsies by adaptive immune effectors is associated with impaired renal tubular cell function and decreased eGFR. These results open new perspectives in evaluating and treating patients with LN, focusing on intrarenal mechanisms of immune cell activation.

We report the case of a 43-year-old man, suffering from ankylosing spondylitis and treated with Infliximab 5 mg/kg every 2 months, with an excellent disease control. During a follow-up consultation, an incipient renal insufficiency is detected. A urine analysis showed haematuria and proteinuria and a renal puncture-biopsy revealed an image of IgA nephropathy.Several cases of IgA nephropathy have been reported in the literature associated with ankylosing spondylitis. Some of them occur in patients treated with antitumour necrosis factor, but it is unclear whether this pathology is caused by the treatment or whether treatment failed to prevent its occurrence.Our clinical case highlights the importance of regular monitoring of renal function in patients with ankylosing spondylitis, as well as urinary spotting.The question of whether the disease itself, the treatment or other factors such as immune dysregulation could be held responsible for kidney disease will be addressed in the discussion.

Background:In patients with lupus nephritis (LN), clinical response to treatment and renal histopathology have been shown to be discordant. No clinical or laboratory markers have to date been shown to reliably portend renal prognosis, in particular renal function impairment.Objectives:To investigate whether per-protocol repeat renal biopsies are predictive of LN relapses and long-term impairment of renal function.Methods:Forty-two patients with an incident biopsy-proven active proliferative (class III/IV ± V) LN from the LN database of the Université catholique de Louvain were included in the present retrospective study. Per-protocol repeat kidney biopsies were performed in all patients after a median time of 24.3 (IQR: 21.3–26.2) months. The NIH activity index (AI) and chronicity index (CI) scores were assessed in both baseline and repeat biopsies. We defined acute glomerular lesions as cellular proliferation, fibrinoid necrosis or karyorrhexis, cellular crescents, hyaline thrombi or wire loops, and leucocyte infiltration, and chronic glomerular lesions as glomerular sclerosis and fibrous crescents, in alignment with the NIH activity and chronicity indices. Similarly, we defined acute tubulointerstitial lesions as mononuclear cell infiltration and chronic tubulointerstitial lesions as interstitial fibrosis and tubular atrophy.Results:Despite a moderate correlation between urinary protein/creatinine (U-P/C) ratios and AI scores at repeat biopsy (r=0.48; P=0.001), ten patients (23.8%) with U-P/C ratios 3). High AI scores in repeat (but not baseline) kidney biopsies were associated with an increased probability and/or shorter time to renal relapse (N=11) following the repeat biopsy (HR: 1.2; 95% CI: 1.1–1.3; P=0.007), independently of proteinuria levels. This association remained significant for the NIH activity index items within the glomerular but not the tubulointerstitial compartment of the kidney biopsies. High NIH CI scores in repeat (but not baseline) kidney biopsies were associated with a sustained increase in serum creatinine levels corresponding to ≥120% of the baseline value (HR: 1.8; 95% CI: 1.1–2.9; P=0.016) through a median follow-up time of 131.5 (IQR: 73.8–178.2) months, being the case also for acute and chronic tubulointerstitial lesions in repeat but not baseline kidney biopsies.Conclusion:Our results highlight the usefulness of per-protocol repeat biopsies as an integral part of the treatment evaluation, also in patients who have shown adequate clinical response. Glomerular lesions consistent with active renal disease portend LN relapses, while tubulointerstitial lesions consistent with active disease and chronic damage portent long-term renal function impairment.Disclosure of Interests:Ioannis Parodis: None declared, Christina Adamichou: None declared, Selda Aydin: None declared, Alvaro Gomez: None declared, Nathalie Demoulin: None declared, Julia Weinmann-Menke: None declared, Frederic Houssiau Grant/research support from: UCB, Consultant of: GSK, Farah Tamirou: None declared

The soluble form of the interleukin 7 receptor (sIL-7R) is produced by fibroblasts after stimulation with proinflammatory cytokines. Increased sIL-7R serum and synovial fluid levels were recently demonstrated in patients with rheumatoid arthritis., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

A 68-year-old woman was transplanted pre-emptively with a kidney from a deceased donor in May 2012. Her immunosuppressive treatment included thymoglobulin, and tacrolimus, mycophenolate mofetyl (MMF), methylprednisolone. Ten months later, a positive urinalysis for decoy cells (figure 1) preceded a rise in creatinine to 2 mg/dL. Blood PCR for BK DNA detected 45 915 copies/mL. Kidney biopsy disclosed BK virus nephropathy (BKVN; figure 2). MMF was withdrawn and tacrolimus decreased to 4 ng/mL trough level. Three months later, the virus was undetectable. Creatinine remained stable over …

Objectives To evaluate, including through repeated renal biopsy, whether the different ISN/RPS classes of proliferative lupus nephritis (LN) have similar short- and long-term responses to immunosuppression and have distinct long-term prognosis. Methods Ninety-eight patients with new onset ISN/RPS proliferative (III, IV-S or IV-G) LN were diagnosed in our institution between 2001 and 2011. Their baseline renal parameters and their primary response to immunosuppressive therapy were compared, based on quarterly collected data during the first year. Long-term followup (mean 76 months) was also available, as well as repeated renal biopsy data, performed in 45 patients after a mean period of 30 months. Activity (range 0-42) and chronicity (range 0-6) indices were computed according to the Morel-Maroger scoring system. Results While baseline mean 24-h proteinuria was higher in Class IV-G patients (n=50) compared to Class III (n=25) and Class IV-S (n=23) and while baseline mean activity index was lower in Class III versus Class IV-S and Class IV-G, serum creatinine, serum albumin and 24-h proteinuria improved similarly over the first year in the 3 pathological classes. Morover, biochemical data collected at last followup did not differ, nor did the activity/chronicity index on repeated renal biopsy, nor the rate of end-stage renal disease or death. Percentages of patients treated with cyclophosphamide, mycophenolate mofetil and azathioprine were similar in the 3 pathological groups. Conclusions Long-term clinical and pathological prognosis of new-onset proliferative LN, can not be predicted by baseline subsetting according to the ISN/RPS classification. Disclosure of Interest None Declared