Background: The complement system has been recently proposed to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). This study evaluated the value of serum and kidney deposited C3 in predicting renal outcomes in AAV. Methods: This was a retrospective study of 47 patients with AAV, who were categorized according to their serum C3 levels as hypo-or normo-complementemic and to those with positive or negative kidney biopsy immunofluorescence (IF) for C3. Baseline characteristics as well as progression to end-stage renal disease (ESRD) between the 2 groups were compared. Results: In total, 23% (11/47) were hypo-complementemic; these patients were older (74 vs. 65 years, p ¼ 0.013), had higher creatinine levels (4.9 vs. 2.2 mg/dL, p ¼ 0.006), were more often hemodialysis dependent (64% vs. 19%, p ¼ 0.009) and progressed more often to ESRD (55% vs. 11%, p ¼ 0.01) compared to normo-complementemic patients (n ¼ 36). On multivariate analysis, serum creatinine at diagnosis (HR ¼ 16.8, 95%CI: 1.354-208.62, p ¼ 0.028) and low serum C3 (HR ¼ 2.492; 95% CI: 1.537-11.567; p ¼ 0.044) were independent predictors for ESRD. Among 25 patients with an available kidney biopsy, 56% had C3 deposition by IF and displayed more often a mixed histological pattern (72% vs. 27%, p ¼ 0.033), low serum C3 levels (42% vs. 18%, p < 0.001) and serious infections during follow-up (57% vs. 18%, p ¼ 0.047) compared to those with negative (n ¼ 11) IF staining. Conclusion: Almost one of four patients with AAV has low C3 levels at diagnosis which is associated with more severe renal disease and worse renal outcomes (ESRD). This should be taken into account in therapeutic and monitoring strategies.

Background Serious infections (SI) are common in patients with ANCA-associated vasculitides (AAV) like granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Real-life data regarding their incidence and predisposing factors—after the introduction of B cell depleting agents—are limited while data quantifying the risk per treatment modality and year of the disease are missing. Here, we aim to describe in details the incidence and the risk factors for SI in a contemporary AAV cohort. Methods Multicenter, observational, retrospective study of AAV patients followed in three tertiary referral centers. Results We included 162 patients with GPA (63%) and MPA (37%), males 51.9%, mean age 60.9 years, ΑΝCA+ 86%, and generalized disease 80%. During follow-up (891.2 patient-years, mean 5.4 years), 67 SI were recorded in 50 patients at an incidence rate of 7.5 per 100 patient-years. The SI incidence rate was higher during induction with cyclophosphamide (CYC) compared to rituximab (RTX, 19.3 vs. 11.3 per 100 patient-years, respectively) while it was lower and comparable between RTX and other regimens (5.52 vs. 4.54 per 100 patient-years, respectively) in the maintenance phase. By multivariate analysis, plasmapheresis (PLEX) and/or dialysis was a strong predictor for an SI during the 1st year after diagnosis (OR = 3.16, 95% CI 1.001–9.96) and throughout the follow-up period (OR = 5.21, 95% CI 1.93–14.07). In contrast, a higher baseline BVAS (OR = 1.11, 95% CI 1.01–1.21) was associated with SI only during the 1st year. Conclusions In this real-life study of patients with AAV, the SI incidence was higher during CYC compared to RTX induction while there was no difference between RTX and other agents used for maintenance therapy. Higher disease activity at baseline and need for PLEX and/or dialysis were independent factors associated with an SI.

Objectives There are limited data regarding health-related quality of life (HRQoL) in patients with ANCA-associated vasculitides (AAVs). We aimed to evaluate the HRQoL in patients with AAVs and compare it to another chronic inflammatory disease like rheumatoid arthritis (RA) and to healthy controls (HC). Methods This was a multicentre, cross-sectional study of patients with AAVs and RA recruited from 3 tertiary rheumatology clinics. HRQoL was assessed with the Short Form 36 Health Survey, which included the physical and mental component summary scores (PCS and MCS). Data from 1,007 HC served as historical controls. Results 66 patients with AAVs and 71 with RA were included. Both AAV and RA patients had significantly lower PCS and MCS scores compared with HC (p&lt; 0.05). HRQoL in AAV patients was worse in patients with microscopic polyangiitis compared with granulomatosis with polyangiitis (physical components) and those with high (VDI ≥ 3) vs. low (VDI &lt; 3) damage scores while it did not differ between those with active (BVASv3 ≥ 1) vs. inactive (BVASv3 &lt; 1) disease. In contrast, in RA patients, HRQoL correlated both with disease activity (assessed by the DAS28-ESR) and functional impairment/damage (assessed by the HAQ). Although overall patients with RA had similar HRQoL compared with those with AAVs, those with active RA had worse HRQoL compared with those with active AAV. Conclusions In patients with AAVs, HRQoL correlated more with organ damage and less with disease activity whereas in RA patients correlated with both. These data emphasize the need for AAV therapies aiming at preventing organ damage and thus improving HRQoL.

<b><i>Introduction:</i></b> Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine, with diverse roles in fibrosis and inflammation, which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-β/Smad signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD). <b><i>Methods:</i></b> We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3), and Smad7 semiquantitatively and quantitatively using computerized image analysis program in different compartments of 50 renal biopsies with GN, and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression, and their role in progression to CKD. <b><i>Results:</i></b> TGF-β1 expression correlated positively with segmental glomerulosclerosis (<i>p</i><b></b>= 0.025) and creatinine level at diagnosis (<i>p</i> = 0.002), while pSmad3 expression with interstitial inflammation (<i>p</i> = 0.024). In glomerulus, concomitant expressions of high Smad7 and medium pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (<i>p</i> = 0.011), intense interstitial inflammation (<i>p</i> = 0.029), and lower serum complement (C) 3 (<i>p</i> = 0.028) and C4 (<i>p</i> = 0.029). We also reported a significant association between pSmad3 expression in glomerular endothelial cells of proliferative GN (<i>p</i> = 0.045) and in podocytes of nonproliferative GN (<i>p</i> = 0.005). Finally, on multivariate Cox-regression analysis, TGF-β1 expression (hazard ratio = 6.078; 95% confidence interval: 1.168–31.627; <i>p</i> = 0.032) was emerged as independent predictor for CKD. <b><i>Discussion/Conclusion:</i></b> TGF-β1/Smad signaling is upregulated with specific characteristics in different forms of GN. TGF-β1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation.

BackgroundANCA associated vasculitides (AAVs) are rare, serious forms of vasculitides. There are limited data regarding the quality of life in patients with AAVs compared to other chronic inflammatory diseases.ObjectivesThe purpose of this study was to compare the quality of life between patients with AAV and those with a chronic inflammatory arthritis such as rheumatoid arthritis (RA).MethodsMulticenter, cross-sectional study of AAV and RA patients followed in three tertiary referral centers. Data from 1007 healthy controls served as historic controls.1 HRQoL was assessed with the Short Form 36 Health Survey (SF-36) which includes physical and mental component summary scores (PCS and MCS). Disease activity were assessed with the Birmingham Vasculitis Activity Score version 3 (BVAS 3, for AAVs) and the DAS28-ESR (for RA) respectively and organ damage/function with the Vasculitis Damage Index (VDI for AAVs) score and Health Assessment Questionnaire (HAQ for RA) scores, respectively.Results66 patients with AAVs (GPA 62%, MPA 29% and EGPA 9%, females 56%, mean age 63.4 years, generalized disease 74%, mean disease duration 6.2 years, remission 73%) and 71 with RA (females 56%, mean age 63.3 years, remission 72%) were included. Both AAV and RA patients had significantly lower PCS and MCS scores compared to healthy controls (p < 0.05) while RA patients had lower PCS and MCS scores compared to AAV patients (p < 0.05). According to disease activity status, there was no difference in the SF-36 scores between those with active (BVAS > 1) and inactive (BVAS < 1) AAV, except for the energy-fatigue component (55.0 ± 21.8 vs. 67.2 ± 20.7, p= 0.038) whereas patients with active RA (DAS28-ESR > 3.2) had lower scores for all SF36 components compared to those with low disease activity (DAS28-ESR < 3.2). Additionally, active RA patients had lower both PCS and MCS scores compared to active AAV patients (p < 0.05). AAV patients with increased damage scores (VDI > 3) had lower PCS score compared to those with less organ damage (VDI < 3), (33.9 ± 10.1 vs. 49.1 ± 10.2, p < 0.001) while RA patients with increased damage/poor functionality (HAQ ≥ 0.75) had lower both PCS and MCS scores compared to those with less damage (HAQ ≤ 0.63), (35.0 ± 7.2 vs. 48.4 ± 8.6, p < 0.001) and (40.5 ± 8.6 vs. 48.2 ± 7.6, p < 0.001 respectively). Compared to patients with AAV, RA patients with increased damage had lower score for the pain component compared to AAV patients (37.7 ± 28.6 vs. 61.2 ± 29.5, p= 0.024).ConclusionIn general, patients with AAV and RA, demonstrate impaired quality of life compared to healthy controls. In the AAV group, quality of life correlated more with organ damage and less with disease activity whereas in RA patients, quality of life correlated both with disease activity and damage. These data emphasize the need for more efficacious therapies for AAV patients that could prevent chronic organ damage and improve quality of life.References[1]Pappa, E., Kontodimopoulos, N. & Niakas, D. Validating and norming of the Greek SF-36 Health Survey. Qual Life Res 14, 1433–1438 (2005).AcknowledgementsSupported in part by the Greek Rheumatology Society and Professional Association of Rheumatologists (ERE-EPERE) and the Special Account for Research Grants (S.A.R.G.), National and Kapodistrian University of Athens, Athens, Greece (DV #12085, 12086).Disclosure of InterestsNone declared