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BACKGROUND: Nucleic acid testing (NAT) for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) has been implemented in several European countries and in the United States, while hepatitis B virus (HBV) NAT is still being questioned by opinions both in favor and against such an option, depending on the HBV endemicity, health care resources, and expected benefits. STUDY DESIGN AND METHODS: This survey was aimed to assess the NAT impact in improving the safety of blood supply in Italy, 6 years after implementation. The study involved 93 Italian transfusion centers and was carried out in 2001 through 2006. A total of 10,776,288 units were tested for the presence of HCV RNA, 7,932,430 for HIV RNA, and 3,405,497 for HBV DNA, respectively. RESULTS: Twenty-seven donations or 2.5 per million tested were HCV RNA–positive/anti-HCV–negative; 14 or 1.8 per million units tested were HIV RNA–positive/anti-HIV–negative; and 197 or 57.8 per million donations tested were HBV DNA–positive/hepatitis B surface antigen–negative. Of the latter, 8 (2.3/106) were collected from donors in the window phase of infection and 189 (55.5/106) from donors with occult HBV. Sixty-eight percent of the latter donors had hepatitis B surface antibody, 74.5 percent of whom with concentrations considered protective (≥10 mIU/mL). CONCLUSION: NAT implementation has improved blood safety by reducing the risk of entering 2.5 HCV and 1.8 HIV infectious units per million donations into the blood supply. The yield of NAT in detecting infectious blood before transfusion was higher for HBV than for HCV or HIV. However, the benefit of HBV NAT in terms of avoided HBV-related morbidity and mortality in blood recipients needs to be further evaluated.

The aim of this study was to define the clinical impact of Herpes simplex virus-1 (HSV-1) DNA detection in the low respiratory tract of hospitalized patients. Forty-nine patients admitted to the University Hospital Tor Vergata, Rome, Italy, from May 2013 to June 2014, were analysed. Inclusion criteria were the presence or absence of HSV-1 DNA in clinical routine bronchoalveolar lavage (BAL) fluid specimens. Nineteen individuals were positive (cases) and 30 negative (controls) for the presence of HSV-1 DNA. The two groups were matched for age, gender and month of BAL collection. Cases and controls differed significantly according to length of stay in hospital (p=0.027), ICU transfer (p=0.02), disease severity (p=0.003), death (p=0.009), haematological and blood chemistry tests. Among cases, survivors and deceased patients differed significantly regarding ICU transfer (p=0.0001), mechanical ventilation (p=0.0048), disease severity (p=0.028) and risk of death (p=0.013). A trend towards higher HSV-1 loads was observed in the cases who died. These results suggest that detection of HSV-1 DNA in BAL fluid specimens is a marker of disease severity and poor outcome. Further prospective studies are necessary to deepen the clinical significance of HSV-1 DNA detection in the lower respiratory tract of hospitalized patients.

Objectives Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis. Methods A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercial techniques. Results The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low–medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0–12 months), and high levels at T0–1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions. Conclusion Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients. Trial registration The Zeus study was registered at https://clinicaltrials.gov, NCT02403115.

Objectives Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes. Methods Here we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques. Results LN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months. Conclusions Anti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN. Trial registration The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).

Background: Belimumab (Benlysta) is currently approved for the treatment of active Lupus despite standard therapy. Few data are available on the efficacy of this drug in lupus nephritis (LN). Methods: 17 LN female followed in two Nephrology Italian Unit received belimumab for a median period of 36 months (range 6–42 months). The indications were: arthralgia in 3 patients, cutaneous manifestations in 2, residual proteinuria in 8, and the need to reduce steroids for severe side effects in 4. Of interest, 1 patient started therapy during Peritoneal Dialysis and continued after kidney transplantation due to non-responsive arthralgias. Results: Arthralgia and skin manifestations resolved in all patients. Proteinuria normalized in three patients and stabilized in all but one of the others. Steroids were indefinitely stopped in six patients (35%) and reduced to around 40% of the basal dosage in the other patients. During belimumab therapy, three extrarenal and one renal SLE flares were diagnosed accounting for a rate of renal flares of 0.02/patient/year. No major adverse events leading to therapy withdrawal occurred. Clinical case: Arthralgia resolved, immunological parameters improved and prednisone could be reduced within few months in the patient who started belimumab during peritoneal dialysis. After kidney transplantation belimumab was stopped but due to arthralgias unresponsive to standard immunosuppressive therapy it was restarted with success. Conclusions: Belimumab allows the achievement of complete response together with the withdrawal or the reduction of corticosteroids in almost all our patients. Of interest its satisfactory use in a patient in peritoneal dialysis and after kidney transplantation.

ObjectiveTo investigate second kidney biopsy as predictor of end-stage kidney disease (ESKD) in active lupus nephritis (LN).MethodsPatients with biopsy-proven LN (International Society of Nephrology/Renal Pathology Society 2003) who had undergone a second kidney biopsy between January 1990 and December 2018 were included. Clinical and histological findings at first and at second biopsy were analysed with Cox proportional hazard models to predict ESKD, defined as start of kidney replacement therapy. Survival curves were calculated with Kaplan-Meier method.ResultsNinety-two patients with LN were included, 87% females, mean follow-up 17.9±10.1 years. Reasons for second kidney biopsy encompassed nephritic flares (n=28, 30.4%), proteinuric flares (n=46, 50%) or lack of renal response (n=18, 19.5%). Class switch from first biopsy occurred in 50.5% of cases, mainly from non-proliferative towards proliferative classes. Class IV remained stable in over 50% of cases. Twenty-five patients (27.2%) developed ESKD, mostly belonging to the nephritic flare group (17/28, 60.7%). Independent predictors of ESKD at second biopsy were activity index (AI; (HR 95% CI) 1.20 (1.03 to 1.41), p=0.022), chronicity index (CI; 1.41 (1.09 to 1.82), p=0.008) and 24h-proteinuria (1.22 (1.04 to 1.42), p=0.013). AI≥2 (log-rank p=0.031), CI >4 (log-rank p=0.001) or proteinuria ≥3.5 g/day (log-rank=0.009) identified thresholds for higher ESKD risk. In a subgroup analysis, glomerular activity and tubular chronicity mostly accounted for AI and CI association with ESKD. No histological or laboratory predictors emerged at first biopsy (95% CI): AI: 0.88 to 1.19; CI: 0.66 to 1.20; proteinuria 0.85 to 1.08.ConclusionsFindings at second but not at first kidney biopsy in patients with persistently active or relapsing LN inform about ESKD development in a long-term follow-up.

Objective.Neutrophil extracellular traps (NET) expose modified antigens for autoantibodies in vasculitis. Little is known about levels and removal pathways of NET in systemic lupus erythematosus (SLE), especially in lupus nephritis (LN). We determined circulating levels and defined NET removal in large subsets of patients with incident SLE (iSLE), some of whom had new-onset nephritis.Methods.Serum levels of NET (ELISA), DNase1/DNase1L3 (ELISA), and DNase activity (functional assay) were determined in 216 patients with iSLE [103 had incident LN (iLN)], in 50 patients with other primary glomerulonephritis, and in healthy controls.Ex vivoNET production by neutrophils purified from a random selection of patients was quantified as elastase/DNA release and by immunofluorescence techniques.Results.Serum NET levels were very high in iSLE/iLN compared to all groups of controls and correlated with anti-dsDNA, C3–C4, and proteinuria; iLN had the highest levels. DNase activity was decreased in iLN compared to SLE (20% had one-half DNase activity) despite similar serum levels of DNase1/DNase1L3. In these cases, pretreatment of serum with protein A restored DNase efficiency; 1 patient was homozygous for a c.289_290delAC variant ofDNASE1L3.Ex vivoNET production by neutrophils purified from LN, SLE, and normal controls was similar in all cases.Conclusion.Patients with iLN have increased circulating NET and reduced DNase activity, the latter being explained by the presence of inhibitory substances in circulation and/or by rareDNase1L3mutations. Accumulation of NET derives from a multifactorial mechanism, and is associated and may contribute to disease severity in SLE, in particular to renal lesions. (Clinical trial registration: The Zeus study was registered atClinicalTrials.gov, study numberNCT02403115).

ObjectivesShort-term predictive endpoints of chronic kidney disease (CKD) are needed in lupus nephritis (LN). We tested response to therapy at 1 year.MethodsWe considered patients with LN who underwent renal biopsy followed by induction therapy between January 1970 and December 2016. LN was assessed using the International Society of Nephrology/Renal Pathology Society (2003) criteria and the National Institute of Health (NIH) activity and chronicity index. The renal outcome was CKD. Response was defined according to EULAR/European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations:complete:proteinuria partial:≥50% proteinuria reduction to subnephrotic levels, (near) normal eGFR; andno response:all the other cases. Logistic regression analysis was employed for 12-month response and Cox regression for CKD prediction.ResultsWe studied 381 patients (90.5% Caucasians). After 12-month therapy, 58%, 26% and 16% of patients achieved complete, partial and no response, respectively, according to EULAR/ERA-EDTA. During a median follow-up of 10.7 (IQR: 4.97–18.80) years, 53 patients developed CKD. At 15 years, CKD-free survival rate was 95.2%, 87.6% and 55.4% in patients with complete, partial and no response at 12 months, respectively (pConclusionsLack of EULAR/ERA-EDTA response at 12 months predicts CKD.

ObjectivesTo evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time.Patients and methodsWe studied a multicentre cohort of 499 patients diagnosed with LN from 1970 to 2016. The 46-year follow-up was subdivided into three periods (P): P1 1970–1985, P2 1986–2001 and P3 2002–2016, and patients accordingly grouped based on the year of LN diagnosis. Predictors of patient and renal survival were investigated by univariate and multivariate proportional hazards Cox regression analyses. Survival curves were compared using the log-rank test.ResultsA progressive increase in patient age at the time of LN diagnosis (pConclusionsClinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival.

Objective The efficacy of rituximab (RTX) in systemic lupus erythematosus (SLE) is a subject of debate. This study was undertaken to investigate the outcomes of RTX treatment in a European SLE cohort, with an emphasis on the role of RTX as a maintenance agent. Methods All patients with SLE who were receiving RTX as induction therapy in 4 centers were included. Patients who received a single course of RTX and those who received RTX maintenance treatment (RMT) were followed up after treatment. Disease flares during the follow-up period were defined as an increase in disease activity and the number or dose of immunosuppressive drugs. Results Of 147 patients, 27% experienced treatment failure at 6 months. In a multivariate analysis, a low number of previous immunosuppressive therapies (P = 0.034) and low C4 levels (P = 0.008) reduced the risk of treatment failure. Eighty patients received RMT over a median of 24.5 months during which 85 relapses, mainly musculoskeletal, were recorded (1.06 per patient). At the time of the last RTX course, 84% of the patients were in remission. Twenty-eight (35%) of 80 patients never experienced a flare during RMT and had low damage accrual. Active articular disease at the time of the first RTX administration was associated with a risk of flare during RMT (P = 0.011). After RMT, relapse-free survival was similar to that in patients receiving a single RTX course (P = 0.72). Conclusion RMT is a potential treatment option for patients with difficult-to-treat disease. Relapses occur during RMT and are more likely in those with active articular disease at the time of the first RTX administration. Relapse risk after RMT remains high and apparently comparable to that seen after a single RTX course.

Autoantibody against phospholipase A2 receptor (anti-PLA2R) is a sensitive and specific biomarker of idiopathic membranous nephropathy (iMN), being found in approximately 70% of iMN patients and only occasionally in other glomerular diseases. However, whereas its diagnostic specificity vs. normal controls and other glomerulonephritides (GN) has been firmly established, its specificity vs. membranous nephropathy associated with various diseases (sMN) has given inconsistent results. The aim of our study was to evaluate the prevalence of anti-PLA2R antibodies in iMN in comparison with various control groups, including sMN. A total of 252 consecutive iMN patients, 184 pathological and 43 healthy controls were tested for anti-PLA2R antibody using indirect immunofluorescence (PLA2R IIFT, Euroimmun). Anti-PLA2R autoantibodies were detectable in 178/252 iMN patients, 1/80 primary GN, 0/72 secondary GN, 9/32 sMN and 0/43 healthy controls, with a diagnostic sensitivity of 70.6%. The diagnostic specificity of anti-PLA2R antibody vs. normal and pathological controls was 100 and 94.6% respectively. However, when the diagnostic specificity was calculated only vs. secondary forms of MN, it decreased considerably to 71.9%. Interestingly enough, 9 out of 10 anti-PLA2R positive patients in the disease control groups had membranous nephropathy associated with various diseases (7 cancer, 1 Crohn's disease, 1 scleroderma). In conclusion, anti-PLA2R positivity in a patient with MN, should not be considered sufficient to abstain from seeking a secondary cause, especially in patients with risk factors for neoplasia. The causal relationship between tumors and anti-PLA2R-induced MN remains to be established, as well as the possible mechanisms through which malignancies provoke autoimmunity.

Glomerular planted antigens (histones, DNA, and C1q) are potential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patients with LN. Prevalent antibody isotypes were defined, levels were determined, and glomerular colocalization was investigated. Renal and circulating antibodies were matched, and serum levels were compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (anti–α-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti–α-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and anti–α-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria>3.5 g/24 hours and creatinine>1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare systemic diseases that usually occur in adulthood. They comprise granulomatosis with polyangiitis (GPA, Wegener’s), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Their clinical presentation is often heterogeneous, with frequent involvement of the respiratory tract, the kidney, the skin and the joints. ANCA-associated vasculitis is rare in childhood but North-American and European cohort studies performed during the last decade have clarified their phenotype, patterns of renal involvement and their prognostic implications, and outcome. Herein, we review the main clinical and therapeutic aspects of childhood-onset ANCA-associated vasculitis, and provide preliminary data on demographic characteristics and organ manifestations of an Italian multicentre cohort.

Background The optimal dosing and the efficacy of rituximab for primary membranous nephropathy (PMN) has not been established. This multicentric prospective study evaluates the efficacy and safety of low-dose rituximab (RTX) therapy in patients with PMN in clinical practice. Methods Thirty-four consecutive patients with PMN and nephrotic syndrome were included and received RTX (375 mg/m 2) once (18 patients) or twice (16 patients). RTX was the first-line therapy for 19 (56%) and the second line for 15 (44%) patients. All patients were followed for 12 months after RTX and 24 for at least 18 months (mean 23.9 ± 18.6 months). Results At 12 months, 5 patients (14.7%) achieved complete response, 10 (29.4%) partial and 19 (55.8%) no response. Response occurred '1/46 months after RTX. At 24 months, the clinical situation was unchanged: two non-responders achieved partial response and two responders relapsed. Responders had significantly higher baseline GFR and lower anti-PLA2R antibodies compared with non-responders. Outcome was similar between one or two doses of RTX (non-responders 55.5 versus 56%, respectively) and between patients who had received previous therapy versus those receiving RTX as first-line therapy (non-responders 40 versus 68%, respectively). In the 15 patients already treated, the response to RTX was comparable to that of previous therapies. Conclusion Low-dose RTX obtains remission in

Few studies have correlated serum biomarkers with renal histology, the gold standard for renal activity, in lupus nephritis (LN). We tested a panel of autoantibodies and complement at the time of kidney biopsy and after treatment. Anti-dsDNA, anti-nucleosome, anti-ribosome P, and anti-C1q antibodies and C3/C4 were measured in 107 patients with LN at the time of renal biopsy and after 6–12 months and were correlated with clinical/histological parameters. At multivariate analysis, high titers of anti-C1q antibodies or of anti-dsDNA antibodies (P=0.005, OR = 8.67, CI: 2.03–37.3) were the independent predictors that discriminate proliferative from nonproliferative LN. All the immunological parameters, except anti-ribosome, showed a significant correlation with activity index but not with chronicity index. Only anti-C1q showed a significant correlation with the amount of proteinuria (R=0.2,P=0.03). None of the immunological parameters were predictive of remission at 6 and 12 months. We found that anti-C1q alone or in combination with anti-dsDNA emerged as the most reliable test in differentiating proliferative and nonproliferative LN. Anti-C1q was the only test correlated with the clinical presentation of LN. After treatment, the titre of the autoantibodies was significantly reduced, but none was predictive of remission.

Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens in renal biopsy samples from patients with LN and determine whether the same autoantibodies can be detected in circulation. Glomeruli were microdissected from biopsy samples of 20 patients with LN and characterized by proteomic techniques. Serum samples from large cohorts of patients with systemic lupus erythematosus (SLE) with and without LN and other glomerulonephritides were tested. Glomerular IgGs recognized 11 podocyte antigens, with reactivity varying by LN pathology. Notably, IgG2 autoantibodies against α-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of α-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti–α-enolase (>15 mg/L) IgG2 and/or anti-annexin AI (>2.7 mg/L) IgG2 were detected in most patients with LN but not patients with other glomerulonephritides, and they identified two cohorts: patients with high anti–α-enolase/low anti-annexin AI IgG2 and patients with low anti–α-enolase/high anti-annexin AI IgG2. Serum levels of both autoantibodies decreased significantly after 12 months of therapy for LN. Anti–α-enolase IgG2 recognized specific epitopes of α-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human α-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against α-enolase and annexin AI predominate in the glomerulus and can be detected in serum.

Objective. We report the first comparison between rituximab (RTX) and either MMF or CYC pulses in the treatment of active LN. Methods. Fifty-four patients with active LN received three methylprednisolone pulses for 3 consecutive days followed by oral prednisone and RTX 1 g at days 3 and 18 (17 patients) or MMF 2-2.5 g/day (17 patients) or six CYC pulses (0.5 g every fortnight) (20 patients). At 4 months MMF, AZA or ciclosporin were associated to prednisone as a consolidation/maintenance therapy in all groups. The outcomes of the three groups were compared at 3 and 12 months. Results. Patients in the RTX group were older, had a longer duration of SLE and LN, had more renal flares, had higher activity and had higher chronicity indexes at renal biopsy than the other two groups. Four patients in each group had acute renal dysfunction and ∼50% had nephrotic syndrome. At 3 months, proteinuria was reduced by 50% in 58.8% of patients on RTX, in 64.7% on MMF and in 63.1% on CYC. At 12 months, complete remission was present in 70.6% of patients on RTX, in 52.9% on MMF, and in 65% on CYC. Partial remission was reached in 29.4% on RTX, 41.2% on MMF, and 25% on CYC. Conclusion. RTX seems to be at least as effective as MMF and CYC pulses in inducing remission. Considering that patients treated with RTX had more negative renal prognostic factors, this drug should be considered a viable alternative for the treatment of active LN. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Objectives. PTPN22 is involved in T-cell activation and its R620W single-nucleotide polymorphism (SNP) has been shown to predispose to different autoimmune diseases. The aims of this study were to investigate the role of the PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated vasculitides (AAVs), and to explore potential associations between the PTPN22 genotype and the disease manifestations. Methods. PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients [143 with granulomatosis with polyangiitis (Wegener’s) (GPA), 102 with microscopic polyangiitis (MPA) and 99 with ChurgStrauss syndrome (CSS)] and in 945 healthy controls. Results. The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls [P = 0.005, � 2 = 7.858, odds ratio (OR) = 1.91], while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P = 0.00012, � 2 = 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, � 2 = 7.258, OR = 1.98), lung involvement (P = 0.0060, � 2 = 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, � 2 = 16.567, OR = 3.73). Conclusion. The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset.

Objectives The objective of this study was to evaluate the clinical features, course, outcome, and prognostic indicators in lupus membranous nephritis (LMN) and to compare data of "pure" LMN vs "mixed" forms. Methods We retrospectively examined medical records and kidney biopsies of 103 patients with a diagnosis of LMN. Results Sixty-seven patients had "pure" LMN and 36 had "mixed" forms. Patients with mixed LMN had more frequent nephrotic syndrome (66.6 vs 44.7%, P = 0.05), low C3 (83.3 vs 62.6%, P = 0.05) and C4 (80.5 vs 52.2%, P = 0.005), anti-DNA positivity (86.0 vs 62.6%, P = 0.03), and a tendency toward a lower creatinine clearance (93 ± 29 vs 112 ± 50 mL/min, P = 0.07). Moreover, mixed membranous nephritis had a higher activity and chronicity index (6.5 ± 2.1 vs 1.4 ± 2.03, P = 0.005 and 2.4 ± 1.7 vs 1.4 ± 1.8, P = 0.0001, respectively). Methylprednisolone pulses and immunosuppressive therapy were more often used in patients with mixed forms (86.1 vs 60.6%, P = 0.016 and 83.3 vs 57.5%, P = 0.008, respectively). After a mean follow-up of 156.5 ± 104.5 months, there was no difference in the 2 subgroups concerning the number of patients achieving remission and patient/renal survival (94.5 vs 94.0% and 85.8 vs 86% at 10 years). At multivariate analysis, serum creatinine at presentation ( P = 0.0013), chronicity index ( P = 0.007), failure of achieving remission ( P = 0.000001), and occurrence of nephritic flares ( P = 0.00167) were independent predictors of chronic renal insufficiency. Conclusions Despite the differences in clinical and histological presentation, a therapy tailored on the grounds of clinical and histological features may reduce the differences in the outcome of white patients with mixed and pure membranous nephritis.

The clinical course of lupus nephritis is characterised by alternation of quiescences and exacerbations. The potential treatment strategies for renal flares are an important issue considering the potential toxicity and the incomplete efficacy of available drugs.1,–,4 Among the new agents for induction of remission, rituximab (RTX), an anti-CD20 monoclonal antibody, has emerged as a potential therapeutic alternative.5,–,8 In this prospective study, we report the first comparison between RTX and cyclophosphamide (CY) in the treatment of relapses of proliferative lupus nephritis (PLN). From April 2006 to January 2010, 24 patients with established PLN and a new renal relapse discontinued all immunosuppressive drugs and received one intravenous methylprednisolone pulse (MPP) (0.5–1 g each) for 3 days and, based on the patients' choice …

Summary Background and objectives The discovery of different podocyte autoantibodies in membranous nephropathy (MN) raises questions about their pathogenetic and clinical meaning. This study sought to define antibody isotypes and correlations; to compare levels in MN, other glomerulonephritides, and controls; and to determine their association with clinical outcomes. Design, setting, participants, & measurements Serum IgG1 ,I gG3 ,a nd IgG4 against aldose reductase (AR), SOD2, and a-enolase (aENO) were measured at diagnosis in 186 consecutive MN patients, in 96 proteinuric controls (36 with FSGS, and 60 with IgA nephropathy), and in 92 healthy people recruited in four Italian nephrology units. Anti-phospholipase A2 receptor (PLA2r) and anti-neutral endopeptidase (NEP) IgG4 were titrated in the same specimens. Association with 1-year follow-up clinical parameters was studied in 120 patients. Results IgG4 was the most common isotype for all antibodies; IgG1 and IgG3 were nearly negligible. IgG4 levels werepositiveinasignificantproportionofMNpatients(AR,34%;SOD2,28%;aENO,43%).Antibodytiterswere higher in MN than in healthy and pathologic controls (P,0.005). Anti-NEP IgG4 did not differ from normal controls (P=0.12). Anti-PLA2r IgG4 was detected in 60% of patients and correlated with anti-AR, anti-SOD2, and anti-aENO IgG4 (P,0.001). In MN patients negative for the whole antibody panel (20%), 1-year proteinuria was lower compared with patients with at least one antibody positivity (P,0.05). Conclusions Our data suggest that IgG4 is the prevalent isotype for antibodies against cytoplasmic antigens of podocytes (AR, SOD2, aENO). Their levels were higher than in other proteinuric glomerulonephritides and in normal controls and were correlated with anti-PLA2r. Only baseline negativity for all known antibodies predicted lower 1-year proteinuria. Clin J Am Soc Nephrol 7: ccc–ccc, 2012. doi: 10.2215/CJN.02170312

Objectives:To evaluate the role of immunological tests for monitoring lupus nephritis (LN) activity.Methods:C3, C4, anti-dsDNA and anti-C1q antibodies were prospectively performed over 6 years in 228 patients with LN.Results:In membranous LN only anti-C1q antibodies differentiated proteinuric flares from quiescent disease (p = 0.02). However, in this group 46% of flares occurred with a normal value of anti-C1q antibodies versus 20% in proliferative LN (p = 0.02). In patients with antiphospholipid antibodies (APL), 33% of flares occurred with normal levels of anti-C1q antibodies versus 14.5% in patients that were APL-negative (p = 0.02). In proliferative LN, anti-C1q antibodies showed a slightly better sensitivity and specificity (80.5 and 71% respectively) than other tests for the diagnosis of renal flares. All four tests had good negative predictive value (NPV). At univariate analysis anti-C1q was the best renal flare predictor (pConclusions:Anti-C1q is slightly better than the other tests to confirm the clinical activity of LN, particularly in patients with proliferative LN and in the absence of APL. All four “specific” tests had a good NPV, suggesting that, in the presence of normal values of each, active LN is unlikely.