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  • BMJ  (8)
  • Pacucci, V. A.  (8)
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  • 1
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    OP0204 LUPUS COMPREHENSIVE DISEASE CONTROL IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: APPLICATION OF A NEW INDEX
    BMJ ; 2020
    In:  Annals of the Rheumatic Diseases Vol. 79, No. Suppl 1 ( 2020-06), p. 127.1-127
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 127.1-127
    Abstract: The main outcomes in SLE patients management are represented by the remission achievement and chronic damage prevention. Even though activity and damage are intimately connected, to date indices including both these outcomes are not available. Objectives: In the present study, we aimed at assessing the application of a new index, the Lupus comprehensive disease control ( LupusCDC ), including disease activity and chronic damage progression. Methods: We performed a longitudinal analysis, including SLE patients according to ACR 1997 criteria, followed-up in the period between January 2014 and December 2018, and with at least one visit per year. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and three different remission levels were evaluated, as reported in Table 1 (1). Table 1. Remission levels considered in the study (1). Remission level Definition Complete Remission ( CR ) No clinical and serological activity (SLEDAI-2K=0) in corticosteroid-free and immunosuppressant-free patients (antimalarials allowed) Clinical remission off-corticosteroids ( ClR-GCoff ) Serological activity with clinical quiescent disease according to SLEDAI-2K in corticosteroid-free patients (stable immunosuppressive therapy and antimalarials allowed) clinical remission on-corticosteroids ( ClR-GCon ) Clinical quiescent disease according to SLEDAI-2K in patients on prednisone 1–5 mg/day (stable immunosuppressants and antimalarials allowed) Chronic damage was registered according to SLICC damage index (SDI). All the patients were evaluated at baseline (T0) and every 12 months (T1, T2, T3, T4). At each time-point, we calculated the prevalence of LupusCDC, defined as remission achievement plus absence of chronic damage progression in the previous one year. We calculated this outcome including separately the different remission levels. Results: According with inclusion criteria, 172 SLE patients were evaluated in the present analysis [M/F 16/156, median age 49 years (IQR 16.7), median disease duration 180 months (IQR 156)]. At first assessment, we observed a mean±SD SDI value of 0.7±1.1. In details, 56 patients (32.5%) showed damage in at least one organ/system and the presence of damage was significantly associated with age (p 〈 0.0001, r=0.3) and disease duration (p=0.0003, r=0.3). During the follow-up, we observed a significant increase in SDI values compared with T0 (T1: mean±DS 0.8±1.3, p 〈 0.0001; T2: 0.8±1.4, p 〈 0.0001; T3: 0.9±1.4 p=0.0001; T4: 1.0±1.5 p 〈 0.0001). In figure 1A and 1B we reported the proportion of patients achieving the different levels of remission and LupusCDC, respectively. In particular, the LupusCDC definition including CR was the most frequently detected in all time-points evaluated (T1: 18.0%; T2: 31.9%; T3: 27.9%; T4: 24.4%), with a significant difference at T2 [LupusCDC(CR) versus LupusCDC(ClR-GCoff), p=0.0002; LupusCDC(CR) versus LupusCDC(ClR-GCon) p=0.0002)], T3 [LupusCDC(CR) versus LupusCDC(ClR-GCoff), p=0.03; LupusCDC(CR) versus LupusCDC(ClR-GCon) p=0.006], T4 [LupusCDC(CR) versus LupusCDC(ClR-GCon), p=0.002]. No significant differences were found when comparing the prevalence of different remission levels and the prevalence of LupusCDC including the corresponding remission. Conclusion: In the present analysis we proposed for the first time a new index including disease activity and chronic damage, in order to evaluate the proportion of SLE patients reaching a comprehensive disease control. We found that CR is most frequently associated with the absence of damage progression. References: [1]Zen M et al. Ann Rheum Dis 2017. Disclosure of Interests: Fulvia Ceccarelli: None declared, Giulio Olivieri: None declared, Lorenzo Dominici: None declared, Alessandra Ida Celia: None declared, enrica cipriano: None declared, Cristina Garufi: None declared, Silvia Mancuso: None declared, Francesco Natalucci: None declared, Valeria Orefice: None declared, Carlo Perricone: None declared, Carmelo Pirone: None declared, viviana antonella pacucci: None declared, Francesca Morello: None declared, Simona Truglia: None declared, Francesca Miranda: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2020-eular.4560
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1481557-6
    detail.hit.zdb_id: 7090-7
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  • 2
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    AB0355 EFFECT OF TOFACITINIB IN TREG /TH17 BALANCE IN RHEUMATOID ARTHRITIS
    BMJ ; 2020
    In:  Annals of the Rheumatic Diseases Vol. 79, No. Suppl 1 ( 2020-06), p. 1477.2-1478
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 1477.2-1478
    Abstract: Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease that can cause progressive articular destruction (1). The imbalance between Tregs and Th17-cells - an effector T-cell subset acting as Treg antagonists – is closely linked to autoimmunity (2). A shift in the Th17/Treg balance towards the pro-inflammatory Th17 side has been reported in many autoimmune disorders including RA (4-5). Tofacitinib is the first janus kinases (JAK) inhibitor (JAKi) approved for the treatment of RA and it binds to and competitively inhibits the kinase domain of JAK3, JAK1 and, to a lesser degree, JAK2. Data on JAKi and Th17 cells/regulatory T cells (Tregs) are only available for ruxolitinib, a JAKi registered for myeloproliferative diseases (6). Objectives: Our project aimed at investigate the possible effect of Tofacitinib on the Treg/Th17 balance in RA patients. Methods: We isolated Peripheral Blood Mononuclear Cells (PBMCs) from patients affected by RA at baseline (T0) and after one month of Tofacitinib therapy (T1). By flow cytometry we characterized Treg and Th17 at T0 and T1. Clinical and laboratory data of the patients were collected in a standardized, computerized and electronically filled form. We assessed the disease activity by using DAS-28 (CRP). Data were expressed as mean(SD) or median (interquartile range, IQR) according to the variables’ distribution. Mann-Whitney and Spearman test were used. The values of P 〈 0.05 were considered statistically significant. Results: We isolated PBMCs from 9 patients with RA (F:M = 7:2, mean age±SD 60±17.4 years; mean disease duration±SD 20±6.6 years, DAS-28 median at T0 4.14 IQR 1.6; at T1 3.08 IQR 1.3). The median percentage of Treg and Th17 at T0 and T1 were respectively: T0 1.85 IQR 0.98 T1 3.12 IQR 1.37; T0 1.64 IQR 1.4, T1 0.6 IQR 1.1. Treg significantly increased after tofacitinib treatment while Th17 showed a tendency in decreasing without achieving a statistical difference (p= 0.003 and p=0.8, respectively) (figure 1). DAS-28 was negatively correlated with Treg number (r = -0.76565, p = 0.00021) and positively with Th17 numbers (r = 0.5816, p = 0.01135). Conclusion: This is the first study that investigated the role of JAKi on the Treg/Th17 balance in RA showing and increase in Treg cells with a concurrent tendency in decrease of Th17 cell population. The restore of the Treg/Th17 balance was associated with the reduction of DAS-28 (CRP). References: [1]McInnes IB et al. Lancet 2017 [2]Fasching P et al. Molecules 2017 [3]Han L et al. Front. Med. 2015 [4]Beringer A et al. Med. 2016 [5]Lippert E et al. Blood 2006 Disclosure of Interests: viviana antonella pacucci: None declared, cristiana barbati: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Fulvia Ceccarelli: None declared, Silvia Mancuso: None declared, Cristina Garufi: None declared, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2020-eular.4403
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1481557-6
    detail.hit.zdb_id: 7090-7
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  • 3
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    POS0118 SMALL FIBER NEUROPATHY EVALUATION IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: A SINGLE CENTER STUDY.
    BMJ ; 2022
    In:  Annals of the Rheumatic Diseases Vol. 81, No. Suppl 1 ( 2022-06), p. 284.1-284
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. Suppl 1 ( 2022-06), p. 284.1-284
    Abstract: Neuropsychiatric involvement represents one of the most relevant Systemic Lupus Erythematosus (SLE) manifestations and it is characterized by a protean spectrum of clinical disorders. Among them, small fiber neuropathy (SFN) could represent a relevant reason for chronic pain and somatosensorial dysfunctions, even if not included in ACR 1999 nomenclature yet. Objectives In the present study we aimed at evaluating the prevalence of SFN among SLE patients with neuropathic pain and identifying significant associations with clinical and laboratory disease features. Methods Consecutive SLE patients (according to ACR 1987 criteria), were screened for neuropathic pain through a specific questionnaire (DN4). Subjects were enrolled to the full protocol in the presence of bilateral limb pain and one of the following: hypoesthesia to touch or prick; pain caused or increased by brushing; tingling, numbness and itching; electric shocks, painful cold or burning pain. We excluded SLE patients with other possible explanation for SFN including diabetes, Sjogren’s syndrome and kidney impairment (eGFR 〈 30 ml/m). For each patient the following data were collected: demographics, medical history, treatments, disease activity (SLEDAI-2K) chronic damage (SLICC damage index ), clinical and laboratory data, including complement level and the main autoantibodies. Each patient enrolled underwent different tools specific for neuropathic pain (such as SFN-SIQ and NPSI), nerve conduction study, quantitative sensory testing (QST) and skin biopsy performed at proximal thigh and distal leg. SFN was diagnosed when intraepidermal nerve fiber density (IENFD) reduction was associated with at least one thermal detection threshold abnormality at QST. A concomitant fibromyalgia (FM) was evaluated by different tools including FIRST, FibroDetect and ACR 2016 criteria. Results Among the 114 recruitable subjects, 58 were excluded because of confounding factors and 25 declined the study. Therefore we enrolled 31 patients (M/F 3/28, median age 50.0 years, IQR 21.0; median disease duration 132.0 months, IQR 197.0; median SLEDAI-2k 0, IQR 4 and median SDI 1, IQR 1.2). FM was identified in 81.8% of subjects according to ACR criteria. SFN was diagnosed in 35.5% of patients; among them, in 81.8% a non-length dependent distribution was recognized while in 18.2% a length-dependent pattern and the large fiber dysfunction were found. SFN was associated with anti-Sm (p=0.03), Raynaud’s phenomenon (p 〈 0.01), low complement levels (p=0.04) and SLEDAI-2k≥4 (p=0.04). Neurovegetative symptoms and pain intensity correlated with distal (p 〈 0.001) and slightly with proximal IENFD reduction (p=0.02 and p=0.04). No significant association was found between FM and SFN or IENFD. Conclusion The present study suggests that SFN is a common finding in SLE and it should be considered in patient with neuropathic pain, somatosensorial and neurovegetative dysfunctions, especially in subjects with low complement levels, high disease activity and Raynaud’s phenomenon. Figure 1. A: SLE patient with normal IENFD. B: SLE patient with low IENFD, consistent with SFN. Disclosure of Interests None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2022-eular.2895
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2022
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  • 4
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    POS0783 LUPUS NEPHRITIS: HISTOLOGICAL FEATURES AND LONG TERM OUTCOMES IN A LARGE SINGLE-CENTRE COHORT
    BMJ ; 2021
    In:  Annals of the Rheumatic Diseases Vol. 80, No. Suppl 1 ( 2021-06), p. 645.1-645
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. Suppl 1 ( 2021-06), p. 645.1-645
    Abstract: In Systemic Lupus Erythematosus (SLE) patients the incidence of lupus nephritis (LN) is about 40% (1) . The rate of progression to end stage renal disease (ESRD) is 4.3-10.1% (2) and renal involvement is a strong predictor of morbidity and mortality. Objectives: To describe clinical, histological features and renal outcomes of LN patients included in our single-center registry reporting data from more than 30 years. Moreover, we examined the correlation between clinical features at LN diagnosis and therapeutic lines used during the course of a 24 years follow-up. Methods: A total of 71 patients were diagnosed with LN from 1989 to 2020. Demographic features and laboratory abnormalities (serum creatinine, 24 hours urine protein, urinary sediment, ds-DNA) at the time of LN diagnosis and at last available follow-up, were evaluated. We also examined renal biopsy performed and the histological classes (proliferative vs non-proliferative). We considered the increase number of therapeutic lines adopted as a negative prognostic factor in response to therapy. Mean (SD) or median (IQR) were used according the variable distribution. T-test and Chi square and Mann-Whitney were used and p-value 〈 0.05 were considered significant. Results: Among 71 patients with LN, 63 (88.7%) were females and 8 (11.3%) males, with a F/M ratio of 6. Median SLE duration was 180 (162) months. The median age at the onset of nephritis was 28 (19.5) years and occurred in median after 12 (60) months from SLE diagnosis. Sixty patients underwent a biopsy: the histology showed class III or IV prolipherative glomerulonephritis in 49 patients (81.6%) and a non-proliferative class in 11 (18.3%) (p 〈 0.0001). Median serum creatinine value, 24 hours urine protein, urinary sediment, anti-ds-DNA at LN onset are reported in Table 1. Induction therapy was performed with cyclofosfamide in 14.5% of cases, mycophenolate in 21.1%, rituximab in 1.3%, cyclosporine A in 1.9% and azathioprine in 4.6%. The lines of therapies adopted during the follow-up ranged between a minimum of 0 and a maximum of 6 lines with a median value of 1. Overall, the median follow-up was 180 (111) months and 30 (21.3%) patients had at least 120 months of follow-up. Median serum creatinine value, 24 hours urine protein, urinary sediment and eGFR last available follow-up are reported in Table 1. Three patients underwent dialysis and 3 kidney transplantation. Eight patients underwent a re-biopsy: 7 (87.5%) had a proliferative class and 1 (12.5%) had a membranous class (p=0.01). Median serum creatinine value, 24 hours urine protein, urinary sediment at re-biopsy are reported in Table 1. In re-bioptized subgroup patients, induction therapies were cyclofosfamide in 50% of cases, mycophenolate in 12.5%, cyclosporine A in 25% and azathioprine in 12.5%. There were not statistically significant differences among the age on LN onset, the time from renal onset to the onset of the disease and the number of therapeutic lines adopted (Figure 1). Conclusion: Among patients with LN the proliferative classes are the most common. At the 15-year follow-up 2,1% had renal transplantation and 2,1% dyalisis. We did not detect any association between age at diagnosis, time from renal impairment and the number of therapeutic lines. References: [1]Fanouriakis A et al. Update EULAR/ERA–EDTA recommendations for the management of lupus nephritis. Ann Rheum Dis 2019. [2]Hanly JG et al. The frequency and outcome of lupus nephritis: results from an international inception cohort study. Rheumatology 2016. Table 1. Laboratory features in SLE patients at LN onset, at last available follow-up and in re-bioptized patients. LN onset (n 71 ) AFTER 10 years long FOLLOW-UP (n 30 ) P value Re-bioptized patients (n 8 ) Serum creatinine (mg/dl ) 0.81 (+/- 0.4) 0.87 (+/- 0.60) 0,07 1.05 (0.45) 24 hours urine protein (mg/24 h ) 3000 (+/- 3707) 330 (+/- 793) 〈 0,00001 5068 (2392) Active urinary sediment 64 patients (45,44%) 2 patients (6.66%) 〈 0,00001 8 patients (100%) Anti-ds-DNA + 30 patients eGFR 〈 50ml/h 12 patients (3.6%) Disclosure of Interests: None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2021-eular.3710
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 1481557-6
    detail.hit.zdb_id: 7090-7
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  • 5
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    SAT0228 PREGNANCY OUTCOME IN SYSTEMIC LUPUS ERYTHEMATOSUS: A MONOCENTRIC COHORT ANALYSIS
    BMJ ; 2020
    In:  Annals of the Rheumatic Diseases Vol. 79, No. Suppl 1 ( 2020-06), p. 1056.1-1057
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 1056.1-1057
    Abstract: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease, affecting prevalently women in childbearing age. Thanks to pre-gestational counseling and multi-disciplinary approach, adopted in daily clinical practice, SLE patients are experiencing even more uncomplicated pregnancies. Objectives: Here, we evaluated pregnancy outcome in a large SLE cohort, compared to a control group including pregnant women without autoimmune diseases. Methods: Pregnant SLE patients (diagnosis made according to ACR 1997 criteria) were included in the present study, conducted in the context of a joint rheumatology/gynecology multi-disciplinary team. For each patient we collected demographic information, medical history, treatments, disease activity (SLEDAI-2K) chronic damage (SLICC damage index ), clinical and laboratory data, including serum complement level and autoantibodies. Pregnancy outcomes were reported longitudinally as well as disease relapses occurring during pregnancy and puerperium. Flares were defined as new onset or worsening disease-related manifestation in any organ/system. Results: Since 2008, 70 consecutive pregnancies occurred in 50 SLE patients [(median age at diagnosis 25 years (IQR 12.2), median age at first pregnancy 33 years (IQR 7), median disease duration 72 months (IQR 120)]. As controls, we evaluated 100 consecutive pregnancies in 100 women without autoimmune diseases [(median age 31 years (IQR 9)] . Table 1 reports the obstetric, fetal and neonatal outcomes of SLE patients compared to control group. A positive outcome in terms of live born infants was experienced in 88.6% of SLE pregnancies and in 88% of control group (p=NS). There were no statistically significant differences in any of the pregnancy outcomes evaluated; however, the percentage of small for gestational ages (SGA) was significantly higher in SLE group (22.8% versus 11.0% P=0.003). A statistical association was found between SGA and positivity for anti-dsDNA, anti-SSA ed anti-SSB (p=0.0001, p=0.01, p=0.04 respectively). Miscarriage was significantly associated with disease-related serologic abnormalities [anti-dsDNA (p=0.0001), low C3 (p=0.0001) and low C4 (p=0.006)] and past smoking habitus (p=0.0001); preterm birth was associated with anti-dsDNA, anti-CL and anti-B2GPI (p=0.001, p=0.0005, p=0.01 respectively). A disease flare was reported in 28 pregnancies (40%) and in 31 puerperium (44.3%). Figure 1 reports SLE relapses divided according to organ involvement. Flare during pregnancy was associated with positivity for anti-SSA (p=0.001), anti-SSB (p=0.01) and a-CL (p=0.006), while puerperium relapses were associated with previous renal involvement (p=0.0005), flare during pregnancy (p=0.01) and chronic damage (p=0.0001). Table 1. Pregnancy outcomes in 50 SLE and 100 controls. LES (Pregnancies N=70 ) Controls (Pregnancies N=100 ) P OBSTETRIC OUTCOME Preterm birth N/% 18/25.7 19/19 NS Gestational hypertension N/% 5/7.1 3/3 NS Gestational diabetes N/% 5/7.1 5/5 NS Pre-eclampsia N/% 2/2.9 1/1 NS FETAL OUTCOME Miscarriages N/% 8/11.4 12/12 NS PR interval elongation N/% 4/6.4 – – IUGR N/% 3/5 1/1 NS NEONATAL OUTCOME SGA 〈 10° centile N/% 16/22.8 11/11 0.003 Weight at birth median-I.Q.R. 2850-688 3250-814 0.003 Apgar 1’ median-I.Q.R. 8-1 8-1 NS Apgar 5’ median-I.Q.R. 9-1 10-1 NS Figure 1. Disease flares during and after 70 SLE pregnancies divided according to organ involvement. Conclusion: The present study confirms the role of pre-gestational counseling and a multi-disciplinary approach in the outcome of SLE pregnancies. Moreover, the high prevalence of disease relapse even more justifies the need for a combined rheumatology/gynecology multi-disciplinary approach. Disclosure of Interests: Carmelo Pirone: None declared, Fulvia Ceccarelli: None declared, Aikaterini Selntigia: None declared, Carlo Perricone: None declared, Simona Truglia: None declared, viviana antonella pacucci: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, Giuseppina Perrone: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2020-eular.3106
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
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  • 6
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    AB0499 LYMPHOID ORGANIZATION IN LUPUS NEPHRITIS: EVALUATING POSSIBLEAUTO ANTIGENS
    BMJ ; 2022
    In:  Annals of the Rheumatic Diseases Vol. 81, No. Suppl 1 ( 2022-06), p. 1376.2-1377
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. Suppl 1 ( 2022-06), p. 1376.2-1377
    Abstract: Lupus nephritis (LN) represent one of the most frequent organ manifestations and one the major cause of morbidity in Systemic Lupus Erythematosus (SLE) patients. Tubule-interstitial infiltrate (TII) represents an independent prognostic factors of renal outcome 1 . Objectives The aim of the study was to evaluate the inflammatory infiltrates organization in kidney biopsies obtained from LN patients and to investigate possible autoantigens for in situ immune response. Methods Paraffin embedded kidney specimens collected since 2017 from SLE patients who underwent a renal biopsy for diagnostic purpose were re-evaluated 2 . Clinical, laboratory and histological data were collected in a standardized, computerized and electronically filled form, including demographics and past medical history. Disease activity was assessed by using SLEDAI-2K and remission in response to therapy was defined as a score 0 of renal item of the SLEDAI 3 . The cellular infiltrate were assessed by hematoxylin-eosin and by immunohistochemistry with a staining of sequential sections for monoclonal antibodies to CD3, CD20, CD21. Staining for detections of LL-37, vimentin and citrulline was made 4 . Serological levels of CXCL13 and anti-vimentin antibodies (AVAs) were evaluated in a subgroup of patients. Results Eighteen paraffin embedded renal specimens with TII, from LN patients were re-evaluated (F:M = 17:1, median age at biopsy-SD years 37-23; median disease duration at date of biopsy-IQR 3-4 years). A histo-morphologic grading score was performed based on the total count of TI lymphocytes and the presence of ectopic lymphoid structures-ELSs (grade 3-G3) (Figure 1). A correlation was found between G3 structures and the absence of renal remission with conventional immunosuppressive therapy (P=0.0026). Samples with G3 foci showed significantly higher intensity of LL37 (P=0.013) and LL37 co-localization (P=0.006) compared to the other lymphocytic infiltrates. No correlation was found among the intensity of vimentin and citrulline and the grade of lymphoid aggregates. A statistically significant inverse correlation between AVAs serum levels and response to therapy was found (P=0.0048). Moreover, higher level of AVAs and CXCL13 were found in patients with G3 structures. To note, two patients underwent anti-CD20 therapy but renal remission was achieved only in the patients displaying G3 structure. Figure 1. Conclusion The study demonstrated that tubule-interstitium involvement is associated with the presence of lymphoid aggregation and poor renal outcome. For the first time we demonstrated that patients with G3 structures had a significant decreased response to immunosuppressant conventional therapies compared to those without ELSs. These results suggest a possible phatogenetic, prognostic and therapeutical role of lymphocytic aggregates. In addiction, LL37, thus NETosis, could have a possible role in inducing the formation of lymphocytic structures. Moreover, patients with a G3 foci showed high serological levels of AVAs and CXCL13, thus, promoting their possible role as circulating biomarkers of the presence of ELSs. References [1]Bajema, I. M. et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int. 93,789–796 (2018). [2]Weening JJ et al. International Society of Nephrology Working Group on the Classification of Lupus Nephritis; Renal Pathology Society Working Group on the Classification of Lupus Nephritis. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004 Feb;65(2):521-30. [3]Gladman DD et al. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29:288-91. [4]Bombardieri M et al. Ectopic lymphoid neogenesis in rheumatic autoimmune diseases. Nat Rev Rheumatol. 2017 Mar;13(3):141-154. Disclosure of Interests None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2022-eular.2366
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2022
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  • 7
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    SAT0223 TUBULO-INTERSTITIAL INFILTRATES IN LUPUS NEPHRITIS
    BMJ ; 2020
    In:  Annals of the Rheumatic Diseases Vol. 79, No. Suppl 1 ( 2020-06), p. 1054.1-1055
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 1054.1-1055
    Abstract: Lupus nephritis (LN) occurs in up to 60% of patients affected by Systemic Lupus Erythematosus (SLE). The presence of inflammatory infiltrates in glomeruli and/or in tubulo-interstitium (TI) plays an important role in terms of prognosis (1). Ectopic lymphoid structures (ELSs) are clusters of organized lymphoid infiltrates forming at sites of chronic inflammation in non-lymphoid organs (2). Data on ELSs in kidneys of SLE patients are scant (3-5). Objectives: The aim of the study was to evaluate the tubule-interstitial infiltrates (TI-I) organization and to investigate the presence of ELSs. Methods: Kidney sections of SLE patients undergoing a renal biopsy for diagnostic purpose were studied; LN was diagnosed according to the 2003 International Society of Nephrology / Renal Pathology Society classification criteria. Clinical, laboratory and histological data were collected in a standardized, computerized and electronically filled form, including past medical history. The presence of lymphoid aggregates and ELS in the kidney sections were firstly evaluated by hematoxylin-eosin (HE). By using immunohistochemistry (IHC), we characterized the infiltrates by identification of T cells (CD3), B cells (CD20) and follicular dendritic cells (CD21). Results: By HE we evaluated 53 kidney samples from LN patients (F:M = 51:2, mean age at biopsy ± SD years 35±7.7; mean disease duration at date of biopsy ± SD 8±8.3 years). TI-I were found in 33 kidney specimens. By HE we identified a well-defined infiltrate pattern resembling ELS in 13 renal samples. In these samples, we confirmed the presence of organized infiltrates by IHC, with evidence of segregated T and B cells areas in most of them. In one sample, the CD21 staining was positive confirming the presence of ELS (Figure 1). Interestingly, this last patient, who failed ciclophosphamide and mycofenolate, responded to rituximab administration and is now in complete LN remission. Moreover TII was negatively correlated with renal remission after induction therapy (P=0.03) independent of the histological class and the induction treatment. Figure 1. Biopsy specimens showing tubulo-interstitial ELS by IHC (10x). Conclusion: Assessment and management of LN patients are greatly facilitated by information obtained by renal biopsy. In the present study the evaluation by HE of 53 kidney samples from patients with LN showed TI-I in 62% of the specimens and a well-defined infiltrate pattern with GC-like features in 39% of those specimens with TI-I, confirmed in IHC. The presence of TII was associated with a worse outcome in response to therapy. Our preliminary results obtained by IHC suggest that ELS could be considered as a biomarker of renal response to B-cell depleting therapy supporting the importance of TI disease. References: [1]Giannakakis K. & Faraggiana T. Histopathology of Lupus Nephritis. Clinic Rev Allerg Immunol 2011 [2]Bombardieri M et al. Ectopic lymphoid neogenesis in rheumatic autoimmune diseases. Nat Rev Rheumatol 2017 [3]Chang A et al. In situ B cell-mediated immune responses and tubulointerstitial inflammation in human lupus nephritis. J Immunol 2011 [4]Shen Y et al. Association of intrarenal B-cell infiltrates with clinical outcome in lupus nephritis: a study of 192 cases. Clin Dev Immunol 2012 [5]Neusser MA et al. Intrarenal production of B-cell survival factors in human lupus nephritis. Mod Pathol 2011 Disclosure of Interests: viviana antonella pacucci: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Konsantinos Giannakakis: None declared, Serena Colafrancesco: None declared, Simona Truglia: None declared, Fulvia Ceccarelli: None declared, Cristina Garufi: None declared, cristiano alessandri Grant/research support from: Pfizer, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2020-eular.1296
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
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    detail.hit.zdb_id: 7090-7
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    AB0395 Evaluation of the organ damage detected by systemic lupus international collaborating clinics/american college of rheumatology (slicc/acr) damage index. a monocentric cross-sectional study on 349 patients affected by systemic lupus erythematosus.
    BMJ ; 2013
    In:  Annals of the Rheumatic Diseases Vol. 72, No. Suppl 3 ( 2013-06), p. A908.2-A908
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 72, No. Suppl 3 ( 2013-06), p. A908.2-A908
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2013-eular.2717
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2013
    detail.hit.zdb_id: 1481557-6
    detail.hit.zdb_id: 7090-7
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