Microparticles Expressing Myeloperoxidase and Complement C3a and C5a as Markers of Renal Involvement in Antineutrophil Cytoplasmic Antibody–associated Vasculitis

Objective.To investigate expression of terminal complement components C3a and C5a on circulating myeloperoxidase (MPO)-positive microparticles (MPO+MP) in relation to disease activity and renal involvement in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Methods.Forty-six clinically well-characterized patients with AAV and 23 age- and sex-matched healthy controls were included. The concentration of MPO+MP expressing C3a and C5a was analyzed from citrate plasma by flow cytometry. Serum levels of C3a and C5a were determined using commercial ELISA. The assessment of vasculitis disease activity was performed using the Birmingham Vasculitis Activity Score (BVAS). Among patients, 23 had active disease with BVAS ≥ 2 and 14 patients had active renal flares.Results.AAV patients had significantly increased expression of C3a and C5a on MPO+MP compared to controls (both p < 0.0001). When the group of patients with active AAV was divided according to the presence of renal activity, the concentration of MPO+MP expressing C3a and C5a was significantly higher in patients with renal involvement compared to patients with nonrenal disease and controls (p < 0.05 and p < 0.01, respectively). The serum levels of C3a were significantly decreased (p < 0.01) in the renal subgroup, while there were no changes in serum levels of C5a comparing the renal and nonrenal groups. There was significant correlation between the disease activity measured by BVAS and the levels of C3a and C5a expressed on MPO+MP.Conclusion.Determination of C3a and C5a on MPO+MP might be considered as a novel biomarker of renal involvement in patients with AAV and may be of importance in the pathogenetic process.

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Proteinuria Indicates Decreased Normal Glomeruli in ANCA-Associated Glomerulonephritis Independent of Systemic Disease Activity

Journal of Clinical Medicine ◽

10.3390/jcm10071538 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1538

Author(s):

Désirée Tampe ◽

Peter Korsten ◽

Philipp Ströbel ◽

Samy Hakroush ◽

Björn Tampe

Keyword(s):

Disease Activity ◽

Systemic Disease ◽

Renal Involvement ◽

Kidney Injury ◽

Antineutrophil Cytoplasmic Antibody ◽

Clinicopathological Characteristics ◽

Renal Outcome ◽

Study Results ◽

Renal Biopsies ◽

Stage Renal Disease

Background: Renal involvement is a common and severe complication of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), potentially resulting in a pauci-immune necrotizing and crescentic ANCA glomerulonephritis (GN) with acute kidney injury (AKI), end-stage renal disease (ESRD) or death. There is recent evidence that the degree of proteinuria at diagnosis is associated with long-term renal outcome in ANCA GN. Therefore, we here aimed to systematically describe the association between proteinuria and clinicopathological characteristics in 53 renal biopsies with ANCA GN and corresponding urinary samples at admission. Methods: A total number of 53 urinary samples at admission and corresponding renal biopsies with confirmed renal involvement of AAV were retrospectively included from 2015 to 2021 in a single-center study. Results: Proteinuria correlated with myeloperoxidase (MPO) subtype, diagnosis of microscopic polyangiitis (MPA) and severe deterioration of kidney function. Proteinuria was most prominent in sclerotic class ANCA GN and ANCA renal risk score (ARRS) high risk attributed to nonselective proteinuria, including both glomerular and tubular proteinuria. Finally, there was no association between proteinuria and systemic disease activity, suggesting that proteinuria reflected specific renal involvement in AAV rather that systemic disease activity. Conclusions: In conclusion, proteinuria correlated with distinct clinicopathological characteristics in ANCA GN, mostly attributed to a reduced fraction of normal glomeruli. Furthermore, proteinuria in ANCA GN reflected specific renal involvement in AAV rather than systemic disease activity. Therefore, urinary findings could further improve our understanding of mechanisms promoting kidney injury and progression of ANCA GN.

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Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort

Mediators of Inflammation ◽

10.1155/2015/328078 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Conti Fabrizio ◽

Ceccarelli Fulvia ◽

Perricone Carlo ◽

Massaro Laura ◽

Marocchi Elisa ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Clinical Laboratory ◽

Renal Involvement ◽

Serum Levels ◽

Activity Measurement ◽

Systemic Lupus ◽

Before And After ◽

Dsdna Antibodies

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status.Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM).Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.;P=0.001). Serositis resulted significantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.;P<0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA − (21.8%,P=0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P=0.7).Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.

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Relationship Between Markers of Platelet Activation and Inflammation with Disease Activity in Wegener’s Granulomatosis

The Journal of Rheumatology ◽

10.3899/jrheum.100735 ◽

2011 ◽

Vol 38 (6) ◽

pp. 1048-1054 ◽

Cited By ~ 34

Author(s):

GUNNAR TOMASSON ◽

MICHAEL LAVALLEY ◽

KAHRAMAN TANRIVERDI ◽

JAVIER D. FINKIELMAN ◽

JOHN C. DAVIS ◽

...

Keyword(s):

Disease Activity ◽

Platelet Activation ◽

Wegener’S Granulomatosis ◽

Antineutrophil Cytoplasmic Antibody ◽

Cd40 Ligand ◽

Wegener's Granulomatosis ◽

Soluble Cd40 Ligand ◽

Monocyte Chemoattractant Protein 1 ◽

Unit Increase ◽

Active Disease

Objective.There remains a need for biomarkers to guide therapy in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Our objective was to determine whether measures of platelet activation or inflammation are associated with disease activity in Wegener’s granulomatosis (WG).Methods.Study subjects were participants in a clinical trial. Soluble CD40 ligand (sCD40L), C-reactive protein, interleukin 6 (IL-6), IL-8, monocyte chemoattractant protein 1 (MCP-1), P-selectin, vascular endothelial growth factor, and proteinase 3 (PR3)-specific ANCA were measured by ELISA using plasma samples obtained at baseline (active disease), at remission, and prior to, during, and after first flares. Disease activity was assessed by the Birmingham Vasculitis Activity Score for WG (BVAS/WG). Association of biomarkers with disease activity was determined with conditional logistic and linear regression.Results.Over a mean followup of 27 months, 180 subjects underwent 2044 visits; markers were measured in 563 samples. Longitudinally, all markers other than IL-6 were associated with disease activity. The strongest associations for active disease at baseline versus remission were observed for sCD40L (OR 4.72, 95% CI 2.47–9.03), P-selectin (OR 6.26, 95% CI 2.78–14.10), PR3-ANCA (OR 9.41, 4.03–21.99), and inversely for MCP-1 (OR 0.36, 95% CI 0.22–0.57). BVAS/WG increased by 0.80 (95% CI 0.44–1.16), 0.83 (95% CI 0.42–1.25), and 0.81 (95% CI 0.48–1.15) per unit-increase in PR3-ANCA, sCD40L, and P-selectin, respectively; and decreased by 1.54 (95% CI 0.96–2.12) per unit-increase in MCP-1.Conclusion.Cytokines arising from within the circulation, including those of platelet activation, correlate with disease activity in WG.

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The Relation of Interleukin 17 (IL-17) and IL-23 to Th1/Th2 Cytokines and Disease Activity in Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.100293 ◽

2010 ◽

Vol 37 (10) ◽

pp. 2046-2052 ◽

Cited By ~ 72

Author(s):

MO YIN MOK ◽

HAI JING WU ◽

YI LO ◽

CHAK SING LAU

Keyword(s):

Disease Activity ◽

Lupus Erythematosus ◽

Serum Levels ◽

Interleukin 17 ◽

Healthy Controls ◽

Th2 Cytokines ◽

Systemic Lupus ◽

Active Lupus Nephritis ◽

Active Lupus ◽

Active Disease

Objective.Interleukin 17 (IL-17) was recently linked to pathogenesis of systemic lupus erythematosus (SLE), but its relation to disease activity has not been well characterized. We examined the relation between serum levels of Th17 (IL-17, IL-23), Th1 (IL-12, interferon-γ), Th2 (IL-10, IL-6, IL-4) cytokines and disease activity in patients with SLE.Methods.Serum cytokines were measured by enzyme linked immunosorbent assays. Disease activity was determined by SLE disease activity index (SLEDAI), anti-dsDNA antibody, and C3 and C4 levels.Results.Serum levels of IL-17 (p < 0.001), IL-6 (p = 0.006) and IL-10 (p < 0.001) were higher in SLE patients (n = 70) compared to healthy controls (n = 36). Higher serum IL-23 level was found in patients with active disease with cutaneous manifestations (p = 0.004) and serositis (p = 0.04) compared to those without. Serum IL-17 level above the detection limit was more frequently found in patients who had active lupus nephritis (11/23, 47.8%) (p = 0.002), nonrenal active disease (9/15, 60%) (p = 0.001), and inactive lupus (21/32, 65.6%) (p < 0.001) compared to healthy controls (0%). Serum IL-17 levels were otherwise comparable between these 3 groups of patients and were not related to SLEDAI, glomerular filtration rate, activity or chronicity score and ISN/RPS criteria class among patients with active lupus nephritis. There was no significant correlation between serum IL-17/IL-23 and Th1 or Th2 cytokine levels.Conclusion.SLE patients had higher serum IL-17 levels than healthy controls. Elevated serum IL-23 was found in patients with inflammatory manifestations including cutaneous involvement and serositis. The lack of correlation between Th17, Th1, and Th2 cytokines suggested independent regulatory mechanisms for these cytokines.

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Efficacy of Rituximab and Plasma Exchange in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis with Severe Kidney Disease

Journal of the American Society of Nephrology ◽

10.1681/asn.2019111197 ◽

2020 ◽

Vol 31 (11) ◽

pp. 2688-2704 ◽

Cited By ~ 2

Author(s):

Marta Casal Moura ◽

Maria V. Irazabal ◽

Alfonso Eirin ◽

Ladan Zand ◽

Sanjeev Sethi ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Kidney Disease ◽

Plasma Exchange ◽

Retrospective Cohort ◽

Controlled Trial ◽

Renal Involvement ◽

Antineutrophil Cytoplasmic Antibody ◽

Remission Induction ◽

Randomized Controlled ◽

Anca Associated Vasculitis

BackgroundTreatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX).MethodsA retrospective cohort study of MPO- or PR3-ANCA–positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73 m2). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared.ResultsOf 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC (n=161) or RTX (n=64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR <15 ml/min per 1.73 m2 at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40], P=0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64], P=0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90], P=0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08], P=0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22], P=0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18], P=0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25], P=0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85], P=0.330).ConclusionsThe apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.

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Hydroxychloroquine modulates elevated expression of S100 proteins in systemic lupus erythematosus

Lupus ◽

10.1177/0961203319846391 ◽

2019 ◽

Vol 28 (7) ◽

pp. 826-833 ◽

Cited By ~ 2

Author(s):

R Wakiya ◽

T Kameda ◽

K Ueeda ◽

S Nakashima ◽

H Shimada ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Renal Involvement ◽

S100 Protein ◽

Severity Index ◽

Serum Levels ◽

Systemic Lupus ◽

Protein Levels ◽

Elevated Expression

Objectives We investigated the effect of hydroxychloroquine (HCQ) on S100A8 and S100A9 serum levels in systemic lupus erythematosus (SLE) patients with low disease activity receiving immunosuppressants. Methods SELENA-SLEDAI, Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum levels of complement factors, anti-dsDNA antibodies, and white blood cell, lymphocyte, and platelet counts were used to evaluate disease activity, cutaneous disease activity, and immunological activity, respectively. Serum S100A8 and S100A9 were measured at HCQ administration and after 3 or 6 months using ELISA. Results S100A8 and S100A9 serum levels were elevated at baseline and the magnitude of decrease from baseline at 3 and 6 months after HCQ administration was greater in patients with renal involvement than in those without (baseline: S100A8, p = 0.034; S100A9, p = 0.0084; decrease: S100A8, p = 0.049; S100A9, p = 0.023). S100 modulation was observed in patients with ( n = 17; S100A8, p = 0.0011; S100A9, p = 0.0002) and without renal involvement ( n = 20; S100A8, p = 0.0056; S100A9, p = 0.0012), and was more apparent in patients with improved CLASI activity scores (improved: S100A8, p = 0.013; S100A9, p = 0.0032; unimproved: S100A8, p = 0.055; S100A9, p = 0.055). No associations were observed for immunological biomarkers. Conclusion HCQ may improve organ involvement in SLE by modulating S100 protein levels, especially in patients with renal or skin involvement.

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Reappraisal of Renal Arteritis in ANCA-Associated Vasculitis: Clinical Characteristics, Pathology, and Outcome

Journal of the American Society of Nephrology ◽

10.1681/asn.2020071074 ◽

2021 ◽

pp. ASN.2020071074

Author(s):

Idris Boudhabhay ◽

Florence Delestre ◽

Guillaume Coutance ◽

Viviane Gnemmi ◽

Thomas Quéméneur ◽

...

Keyword(s):

Risk Score ◽

Renal Involvement ◽

External Validation ◽

Multivariable Analysis ◽

Antineutrophil Cytoplasmic Antibody ◽

Prior History ◽

Clinicopathologic Characteristics ◽

Anca Associated Vasculitis ◽

Poor Outcomes ◽

Stage Renal Disease

Background Renal involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with poor outcomes. The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail. Methods In a multicenter cohort of AAV patients with renal involvement, we sought to describe the clinicopathologic characteristics of patients with AAV who had renal arteritis at diagnosis and to retrospectively analyze their prognostic value. Results We included 251 patients diagnosed with AAV and renal involvement between 2000 and 2019, including 34 patients (13.5%) with arteritis. Patients with AAV-associated arteritis were older and had a more pronounced inflammatory syndrome compared with patients without arteritis; they also had significantly lower renal survival (P=0.01). In multivariable analysis, the ANCA renal risk score, age at diagnosis, prior history of diabetes mellitus, and arteritis on index kidney biopsy were independently associated with end-stage renal disease. The addition of the arteritis status significantly improved the discrimination of the ANCA renal risk score, with a concordance index (C-index) of 0.77 for the ANCA renal risk score alone versus a C-index of 0.80 for the ANCA renal risk score plus arteritis status (P=0.008); ESRD-free survival was significantly worse for patients with an arteritis involving small arteries who were classified as having low or moderate risk according to the ANCA renal risk score. In two external validation cohorts, we confirmed the incidence and phenotype of this AAV subtype. Conclusions Our findings suggest that AAV with renal arteritis represents a different subtype of AAV with specific clinical and histologic characteristics. The prognostic contribution of the arteritis status remains to be prospectively confirmed.

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A Rare Case of Digital Ischemia and Gangrene in ANCA-Associated Vasculitis with Review of the Literature

Case Reports in Rheumatology ◽

10.1155/2017/2421760 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Richard A. Lau ◽

Ramandeep Bains ◽

Duminda Suraweera ◽

Jane Ma ◽

Emil R. Heinze ◽

...

Keyword(s):

Granulomatosis With Polyangiitis ◽

English Literature ◽

Renal Involvement ◽

Antineutrophil Cytoplasmic Antibody ◽

High Dose ◽

Eosinophilic Granulomatosis With Polyangiitis ◽

Proteinase 3 ◽

Anca Associated Vasculitis ◽

Digital Ischemia

This paper describes one patient with Antineutrophil Cytoplasmic Antibody- (ANCA-) associated vasculitis who initially presented with multiple ischemic fingers and toes. On further evaluation, the patient was also found to have pulmonary-renal involvement and episcleritis. The diagnosis was supported with a positive cANCA (anti-proteinase 3) and a bronchoscopy consistent with diffuse alveolar hemorrhage. Although the patient refused a tissue biopsy, clinical presentation including nasal ulceration, sinus congestion, and epistaxis and anti-proteinase 3 antibody were more consistent with Granulomatosis with Polyangiitis (GPA) rather than Microscopic Polyangiitis (MPA) or Eosinophilic Granulomatosis with Polyangiitis (EGPA) based on the recently presented ACR/EULAR Provisional 2017 Classification Criteria for GPA (Luqmani et al., 2016). The patient responded well to therapy including high dose steroids and cyclophosphamide, with improvement of all organs involved and had no further digital ischemia or gangrene on follow-up. We include a review of the English literature summarizing presentation, management, and outcome of 16 similar cases.

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AB0500 CLINICAL CHARACTERISTICS AND POTENTIAL BIOMARKERS FOR DISEASE ACTIVITY OF PATIENTS WITH ANCA ASSOCIATED VASCULITIS: A MONOCENTER STUDY IN CHINA

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2533 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1548-1548

Author(s):

Y. Liu ◽

L. MA ◽

L. Jiang

Keyword(s):

Disease Activity ◽

Granulomatosis With Polyangiitis ◽

Antineutrophil Cytoplasmic Antibody ◽

Chinese Patients ◽

Eosinophilic Granulomatosis With Polyangiitis ◽

American College Of Rheumatology ◽

Chapel Hill ◽

Anca Associated Vasculitis ◽

Incident Cases

Background:Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are a group of multisystem, autoimmune, inflammatory disease characterized by pauci- necrotizing vasculitis affecting small blood vessels. The clinical manifestations of the AAV are diverse and can be confined to one organ, or multiple organs and even life-threatening. However, there has been no specific index for assessing the activity of AAV at diagnosis.Objectives:The aim of this study was to describe the clinical and serological features of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in eastern China using data from a hospital-based study. And looking for indicators that can predict disease activity.Methods:We retrospectively studied patients with newly diagnosed AAV evaluated from January 1, 2009, to December 31, 2018. In total, 219 patients diagnosed were classified according to the American College of Rheumatology classification criteria and/or revised Chapel Hill 2012 definitions, and their clinical and serological features were evaluated. The association of laboratory data with disease activity was assessed via regression models.Results:Of 219 incident cases of AAV, 37/219 (16.9%) had granulomatosis with polyangiitis (GPA), 172/219 (78.5%) were microscopic polyangiitis (MPA), and 10/219 (4.6%) had eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis of patients with GPA were 51.5 years MPA were 61.7 years, and EGPA were 49.8 years, respectively. Patients with MPA were significantly older than GPA and EGPA at diagnosis (p<0.001). ANCAs tested positive in 207 (94.5%) of cases: 167 (80.7%) were MPO-ANCA and 40 (19.3%) were PR3-ANCA. Lung, skin, nervous system symptoms were the most common in EGPA. For GPA, ear–nose–throat (ENT) symptoms and lungs involvement were the most common. Renal and lung involvement occurs most frequently in MPA. In the multivariable logistic regression analysis, higher anti-MPO antibody (149.4 IU/ml), higher hypersensitive c-reactive protein (hs-CRP, 62.5 mg/L), lower hemoglobin (113.5g/L), and higher complement 4 (C4, >0.215 g/L) were proved to be independent risk factors for active disease. Further research showed that C4 had higher sensitivity (70.0%) and specificity (83.4%) than the other three indicators.Conclusion:MPO-ANCA-positive MPA is the most common form of AAV in Chinese patients. Serum C4 concentrations at diagnosis might be a useful biomarker of disease activity in AAV.References:[1]Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.Arthritis Rheum2013, 65:1-11.[2]Choi H, Kim Y, Jung SM, Song JJ, Park Y-B, Lee S-W. Low serum complement 3 level is associated with severe ANCA-associated vasculitis at diagnosis.Clinical and Experimental Nephrology2018, 23:223-230.[3]Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis.Arthritis Rheum1990, 33:1101-1107.[4]Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis).Arthritis Rheum1990, 33:1094-1100.[5]Mukhtyar C, Lee R, Brown D, Carruthers D, Dasgupta B, Dubey S, et al. Modification and validation of the Birmingham Vasculitis Activity Score (version 3).Ann Rheum Dis2009, 68:1827-1832.[6]Markiewski MM, Lambris JD. The role of complement in inflammatory diseases from behind the scenes into the spotlight.Am J Pathol2007, 171:715-727.Disclosure of Interests:None declared

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POS0110 ASSOCIATION OF miR-155 AND miR-34a EXPRESSION IN LUPUS NEPHRITIS RENAL TISSUE WITH DISEASE ONSET AND OUTCOMES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3761 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 266.1-266

Author(s):

C. Di Mario ◽

L. Petricca ◽

M. R. Gigante ◽

S. Costanzi ◽

G. Vischini ◽

...

Keyword(s):

Lupus Nephritis ◽

Disease Activity ◽

Iga Nephropathy ◽

Lupus Erythematosus ◽

Clinical Laboratory ◽

Demographic Data ◽

Renal Involvement ◽

Disease Onset ◽

Control Group ◽

Complement Components

Background:Epigenetic factors such as non-coding RNA (miRNA) have been shown to be deregulated in Systemic Lupus Erythematosus (SLE). In mouse models, different miRNAs have been associated with lupus nephritis (LN), one of the most severe manifestations of the disease1.Objectives:To evaluate the expression of miR-155 and miR-34a in renal tissues as biomarkers of organ involvement and inflammatory tissue activity in patients with LN.Methods:Thirty-two SLE patients with LN (age: 32.2 ± 9.2 years) with active renal involvement undergoing ultrasound-guided renal biopsy were enrolled between 2010 and 2019. The nephritic manifestation was present in 13 (41%) patients at disease onset (early-LN SLE), while 19 (59%) patients showed a renal involvement after disease onset (long-LN SLE, mean disease duration at LN onset: 7.3 ± 5.7 years). Twelve age-matched patients with IgA nephropathy were enrolled as control group. Clinical, laboratory and demographic data were collected for each patient. Disease activity was recorded using SLEDAI-2K and renal activity, using the total SLEDAI-2K fraction including the items related to the renal involvement. MiR-155 and miR-34a expression in renal tissues was carried out by extraction of total RNA from paraffin-preserved biopsies and was evaluated, after a retrotrascription protocol, using real-time PCR by relative quantification considering the ΔCt (Ct miRNA- Ct housekeeping gene)2.Results:MiR-155 and miR-34a expression in renal tissues was higher in LN-SLE patients as compared to IgA nephropathy patients (ΔCt miR-155: 9.4 ± 10.1 vs 21.9 ± 3.6, p<0.01; ΔCt miR-34a: 10.1 ± 9.8 vs 19.2 ± 3.1, p=0.02). MiR-155 and miR-34a expression in LN-SLE patients renal tissues was comparable in the different histological classes. Furthermore, a direct correlation was observed between the expression of miR-155 and miR-34a (r = 0.91, p <0.001). Dividing patients based on nephritic onset, SLE patients with long-LN showed higher expression of miR-155 (ΔCt 6.1 ± 8.7) and miR-34a (ΔCt 7.1 ± 9.0) as compared to patients with early-LN (miR-155: ΔCt 13.4 ± 10.6 p = 0.08; miR-34a: ΔCt 15.1 ± 9.5 p = 0.02) or patients with IgA nephropathy (miR-155 p<0.01 and miR-34a p<0.01). Moreover, in early-LN SLE it was observed an inverse correlation between miR-34a expression and C3 and C4 complement components (r=-0.7.2; p=0.05 and r=-0.86; p=0.01, respectively) and a direct correlation between miR-155 and 24h-UP (r=0,67; p=0.03). Considering SLE patients with early-LN, the expression of miR-34a was slightly significant in patients who had relapsed (ΔCt 8.2 ± 11.4 vs ΔCt 18.4 ± 7.9 p = 0.08), although no correlation emerged between the expression of miR-155 and miR-34a at the time of the biopsy and with disease activity indices.Conclusion:MiR-155 and miR-34a may represent tissue biomarkers of inflammatory activation in SLE patients with LN; in particular, the higher expression of these miRNA in long-LN and the correlation between miR-155 expression with p24h-UP in early-LN could indicate a possible role of these biomarkers in renal involvement in patients with SLE with later renal onset. The increased expression of miR-34a could give indications of a disease recurrence suggesting a closer monitoring of patients.References:[1]Leiss H et al. Plosone 2017.[2]Alivernini S et al. Nat Commun 2018.Disclosure of Interests:None declared

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