scholarly journals Serum IgG2 antibody multi-composition in systemic lupus erythematosus and in lupus nephritis (Part 2): prospective study

Rheumatology ◽  
2020 ◽  
Author(s):  
Maurizio Bruschi ◽  
Gabriella Moroni ◽  
Renato Alberto Sinico ◽  
Franco Franceschini ◽  
Micaela Fredi ◽  
...  

Abstract 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).

Lupus ◽  
2021 ◽  
pp. 096120332098390
Author(s):  
Ayako Wakamatsu ◽  
Hiroe Sato ◽  
Yoshikatsu Kaneko ◽  
Takamasa Cho ◽  
Yumi Ito ◽  
...  

Objectives Anti-ribosomal P protein autoantibodies (anti-P) specifically develop in patients with systemic lupus erythematosus. Associations of anti-P with lupus nephritis (LN) histological subclass and renal outcome remain inconclusive. We sought to determine the association of anti-P and anti-double-stranded DNA antibody (anti-dsDNA) with renal histology and prognosis in LN patients. Methods Thirty-four patients with LN, having undergone kidney biopsy, were included. The 2018 revised ISN/RPS classification system was used for pathophysiological evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 for > 3 months. Results Six patients (17.6%) were positive for anti-P and 26 (76.5%) for anti-dsDNA. Among the six patients with anti-P, one did not have anti-dsDNA, but did have anti-Sm antibody, and showed a histological subtype of class V. This patient maintained good renal function for over 14 years. The remaining five patients, who had both anti-P and anti-dsDNA, exhibited proliferative nephritis and were associated with prolonged hypocomplementemia, and the incidence of CKD did not differ from patients without anti-P. Conclusion Although this study included a small number of patients, the results indicated that histology class and renal prognosis associated with anti-P depend on the coexistence of anti-dsDNA. Further studies with a large number of patients are required to confirm this conclusion.


2019 ◽  
Vol 1 (9) ◽  
pp. 53-57
Author(s):  
T. N. Gavva ◽  
L. V. Kuzmenkova ◽  
Yu. N. Fedulaev ◽  
T. V. Pinchuk ◽  
D. D. Kaminer ◽  
...  

A case of lung damage in systemic lupus erythematosus (SLE) in a 33-year-old woman is described. This case is of clinical interest due to the complexity of diagnosis due to the fact that SLE is a disease with diverse clinical manifestations involving many organs and systems, which often makes it difficult to timely recognize the onset of the disease. SLE still remains a challenge and requires special attention to the patient s history, clinical and laboratory parameters of the patient, as well as specific immunological examinations.


2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Haider S Al-Hadad ◽  
Aqeel Abbas Matrood ◽  
Maha Abdalrasool Almukhtar ◽  
Haider Jabur Kehiosh ◽  
Riyadh Muhi Al-Saegh

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease. Few biomarkers for SLE have been validated and widely accepted for the laboratory follow-up of inflammatory activity. In SLE patients, with lupus nephritis (LN), complement activation leads to fluctuation of serum C3 and C4 that are frequently used as clinicalm biomarker of disease activity in SLE. Patients and Methods: In this study the number of patients were 37, seven patients were excluded for incomplete data collection, 28 were females ,2 were males. The duration of the study is two years from 2015 to 2017. Patients were considered to have SLE and LN according to American College of Rheumatology (ACR) criteria, and International Society of Nephrology/ Renal Pathology Society (ISN/RPS). All patients were evaluated withm clinical presentation, laboratory investigations. Our patients underwent kidney biopsy according to standard procedure by Kerstin Amann, and their tissue specimens were studied in the laboratory with light microscope (LM) and immunofluorescence microscope reagents. The relationship between the serological markers and immunofluorescence deposits in kidney biopsy of all patients were studied using the statistical analysis of Pearson correlation and single table student's T test. A P value 0.05 was considered statistically significant. Results: The granular pattern of IF deposits was present in all LN patients, and in more than two third of patients these IF deposits presented in glomerular, tubular, and mesangium sites. While less than one third of patients had IF deposits in the mesangium only. There was no statistically significant correlation between serum ANA, anti-dsDNA, and IF deposits of different types. There was significant correlation between serum C3 and C4 hypocomplementemia and IgG immune deposits in kidney biopsy, and there was significant relationship between serum C3 hypocomplementemia and full house immunofluorescence (FHIF) deposits inm kidney biopsy.Conclusions:Immunofluorescence deposits is mainly granular pattern in LN patients. There was no significant association between serum ANA, anti-dsDNA, and immune deposits in kidney tissue. Immunofluorescence deposits of IgG type correlates significantly with serum C3 and C4 hypocomplemetemia, and these immune deposits in association with low complement levels correlates with LN flare. There was significant correlation between C3 hypocomplementemia and FHIF.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1048.1-1048
Author(s):  
W. Hu

Background:Classical lupus nephritis (LN) is characterized by glomerular immune complex(IC) deposition with glomerular proliferation, basement membrane destruction and cell infiltration. Non-IC mediated renal injury with thrombotic microangiopathy (TMA) was also reported in patients with systemic lupus erythematosus (SLE-renal TMA), but most studies were reported in patients with both LN and renal TMA.Objectives:In this study, clinical features and outcomes of SLE-renal TMA in absence of obvious IC in SLE patients were analyzed.Methods:Patients with glomerular TMA and/or vascular TMA in the absence of obvious subendothelial or epithelial immune deposits were screened out from 2332 biopsied in SLE patients who underwent first renal biopsy from January 2005 to August 2016. Their clinical, histological features and outcomes were retrospectively analyzed.Results:In 2332 renal biopsies obtained from SLE patients, 257 (11.0%) showed renal TMA, of which 237 showed both renal TMA and LN, and 20 biopsies had only renal TMA (SLE-renal TMA). There were 2 males and 18 females with an average age of (25 ± 10) years. The median course of SLE and LN were 3.0(1.0, 6.0) and 0.8(0.5, 1.9) months. All 20 patients deserved acute kidney injury, of which 11 (55%) needed renal replacement therapy (RRT) and 12 (60%) were nephrotic syndrome. Blood system involvement was found in all cases, including 13 cases (65.0%) with TMA triad (microvascular hemolytic anemia, thrombocytopenia and elevated lactate dehydrogenase).Pathological examination showed that 17 cases (85.0%) had both glomerular TMA and vascular TMA. Immunofluorescence and electron microscopy showed that 8 cases (40%) had no IC deposition in glomerulus and 12 cases (60%) had only IC deposition in mesangium. Acute tubulointerstitial lesions in patients requiring RRT were more serious than those no needing for RRT((43.6±24.9) %vs(21.7±20.1) %,P=0.047). The fusion range of foot process was positively correlated with proteinuria (r2= 0.347,P=0.006).All patients received high-dose methylprednisolone pulse therapy. Four patients received plasma exchange and three patients received gamma globulin, respectively. Eleven patients requiring RRT all stop RRT in a median time of 16.0 (9.0, 30.0) days. During a median follow-up of 58.0 (36.0, 92.3) months, complete remission (CR) was obtained in 15 cases, partial remission in 4 cases and no remission in 1 case. Six cases (30%) relapsed. No case died or progressed to end stage renal disease.Conclusion:Renal injury characterized by TMA is not uncommon in SLE renal biopsy cases. The clinical manifestation is special and the renal injury is serious. The renal outcome is good by intensive immunosuppressive therapy. It should be considered as a unique type of renal injury in SLE.References:[1]Moake JL. Thrombotic microangiopathies. N Engl J Med. 2002. 347(8): 589-600.[2]Anders HJ, Weening JJ. Kidney disease in lupus is not always ‘lupus nephritis’. Arthritis Res Ther. 2013. 15(2): 108.[3]Song D, Wu LH, Wang FM, et al. The spectrum of renal thrombotic microangiopathy in lupus nephritis. Arthritis Res Ther. 2013. 15(1): R12.[4]Hu WX, Liu ZZ, Chen HP, Zhang HT, Li LS, Liu ZH. Clinical characteristics and prognosis of diffuse proliferative lupus nephritis with thrombotic microangiopathy. Lupus. 2010. 19(14): 1591-8.[5]Tomov S, Lazarchick J, Self SE, Bruner ET, Budisavljevic MN. Kidney-limited thrombotic microangiopathy in patients with SLE treated with romiplostim. Lupus. 2013. 22(5): 504-9.[6]Li C, Yap D, Chan G, et al. Clinical Outcomes and Clinico-pathological Correlations in Lupus Nephritis with Kidney Biopsy Showing Thrombotic Microangiopathy. J Rheumatol. 2019 .[7]Chen MH, Chen MH, Chen WS, et al. Thrombotic microangiopathy in systemic lupus erythematosus: a cohort study in North Taiwan. Rheumatology (Oxford). 2011. 50(4): 768-75.[8]Park MH, AUID- Oho, Caselman N, Ulmer S, Weitz IC, AUID- Oho. Complement-mediated thrombotic microangiopathy associated with lupus nephritis. Blood Adv. 2018. 2(16): 2090-2094.Disclosure of Interests:None declared


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Mette U. Fredskild ◽  
Sharleny Stanislaus ◽  
Klara Coello ◽  
Sigurd A. Melbye ◽  
Hanne Lie Kjærstad ◽  
...  

Abstract Background DSM-IV states that criterion A for diagnosing hypomania/mania is mood change. The revised DSM-5 now states that increased energy or activity must be present alongside mood changes to diagnose hypomania/mania, thus raising energy/activity to criterion A. We set out to investigate how the change in criterion A affects the diagnosis of hypomanic/manic visits in patients with a newly diagnosed bipolar disorder. Results In this prospective cohort study, 373 patients were included (median age = 32; IQR, 27–40). Women constituted 66% (n = 245) of the cohort and 68% of the cohort (n = 253) met criteria for bipolar type II, the remaining patients were diagnosed bipolar type I. Median number of contributed visits was 2 per subject (IQR, 1–3) and median follow-up time was 3 years (IQR, 2–4). During follow-up, 127 patients had at least one visit with fulfilled DSM-IV criterion A. Applying DSM-5 criterion A reduced the number of patients experiencing a hypomanic/manic visit by 62% at baseline and by 50% during longitudinal follow-up, compared with DSM-IV criterion A. Fulfilling DSM-5 criterion A during follow-up was associated with higher modified young mania rating scale score (OR = 1.51, CL [1.34, 1.71], p < 0.0001) and increased number of visits contributed (OR = 1.86, CL [1.52, 2.29], p < 0.0001). Conclusion Applying the stricter DSM-5 criterion A in a cohort of newly diagnosed bipolar patients reduced the number of patients experiencing a hypomanic/manic visit substantially, and was associated with higher overall young mania rating scale scores, compared with DSM-IV criterion A. Consequently, fewer hypomanic/manic visits may be detected in newly diagnosed bipolar patients with applied DSM-5 criterion A, and the upcoming ICD-11, which may possibly result in longer diagnostic delay of BD as compared with the DSM-IV.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
May Nwe Lwin ◽  
Christopher Holroyd ◽  
Dinny Wallis ◽  
Saul Faust ◽  
Hans De Graaf ◽  
...  

Abstract Background/Aims  The coronavirus disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for over 120,000 UK deaths. Those with chronic inflammatory conditions or receiving immunosuppressive medications are at higher risk of COVID-19 than the general population. As a result, rheumatology patients taking b- or ts-DMARDs were advised to shield. We planned to observe COVID-19 related symptoms and anxiety levels reported by rheumatology patients during the pandemic. Methods  From April 2020, 1,004 rheumatology patients from an advanced therapy database were invited to participate in the adult ImmunoCOVID study to collect daily symptoms (fever, cough, shortness of breath (SOB), sore throat, blocked nose, red-eye, headache, fatigue, joint pain, muscle pain, chills, nausea, diarrhoea and vomiting, loss of senses) and anxiety level using an online portal. Loss of senses were not recorded until week 7 as these were not officially recognized at the pandemic onset. Results  153 patients (rheumatoid arthritis, n = 75, psoriatic arthritis, n = 28, Axial spondyloarthropathy, n = 24, systemic lupus erythematosus, n = 2 and other connective tissue diseases, n = 24) consented and participated. By week 25, 142 patients remained. Among those, 36.57% (±6.09%) (average (±SD)) reported no symptoms over the 25 week period. The main symptoms reported were joint pain (mean=47.94%) followed by fatigue (27.17%). Few patients reported fever (0.94%), cough (8.34%), SOB (4.53%), or loss of senses (1.11%) with more symptoms reported during the first 8 weeks (April/May 2020) and another increase in September/October 2020. The anxiety score (pragmatic 10-point scale) mean (±SD) was 5.60 (±0.34) and remained elevated throughout the study though higher when lockdown began. Conclusion  During the first peak of SARS-CoV-2, the number of patients reporting COVID-19 symptoms appeared high and was associated with high levels of anxiety. As only a small number have been swab-tested, this may suggest that larger numbers of untested individuals have had COVID-19 with mild symptoms. Features of inflammatory rheumatic illnesses may mimic COVID-19 symptoms and create diagnostic difficulty (joint pain and fatigue) whilst anxiety may lead to over-reporting of symptoms in the absence of infection. The key symptoms of fever, cough and SOB were less common and may be most reliable. Disclosure  M. Lwin: None. C. Holroyd: None. D. Wallis: None. S. Faust: None. H. De Graaf: None. C.J. Edwards: Honoraria; Abbvie, Biogen, BMS, Celgene, Fresenius, GSK, Janssen, Lilly, Mundipharma, Pfizer, Roche, Sanofi, UCB. Member of speakers’ bureau; Abbvie, Biogen, BMS, Celgene, Janssen, Lilly, Sanofi, Pfizer, Roche. Grants/research support; Abbvie, Biogen, Pfizer. P051 Table 1:patient reported symptoms and anxiety score from immunoCOVID studyWeek & (number of participants)Fever (%)Cough (%)SOB (%)Joint pain (%)Fatigue (%)Loss of senses (%)No symptoms (%)Tested (n)Test positive (n)Anxiety score1 (26)3.857.6911.5446.1530.77NA30.77006.312 (42)2.3311.639.3052.3834.88NA28.57005.833 (69)1.4514.494.3552.1737.68NA23.19415.884 (92)1.0911.966.5254.3531.52NA27.17206.225 (110)0.0011.716.3145.9533.33NA30.00006.156 (108)0.0010.193.7050.0026.85NA34.26205.747 (119)0.8410.084.2049.5828.57NA34.45205.938 (120)0.007.505.0051.6734.170.8329.17305.629 (124)0.817.263.2352.4229.840.8136.29405.6410 (118)0.008.473.3948.3129.660.8534.75205.2811 (116)0.858.476.7849.1529.661.6933.62305.6512 (131)0.006.114.5856.4926.720.7635.11205.4513 (110)0.916.362.7350.0029.091.8242.73105.4414 (121)0.837.442.4847.1125.620.8339.67805.2815 (100)1.007.003.0046.0023.001.0041.00405.4816 (114)0.887.893.5139.4725.441.7542.98905.2717 (105)0.008.573.8144.7622.860.9543.81425.1018 (107)0.006.543.7443.9319.630.9343.93405.3019 (99)0.005.052.0240.4019.191.0145.45505.0820 (110)0.914.552.7350.9124.550.9139.09NA0Missing data21 (106)0.946.602.8350.0020.750.9439.62405.2822 (104)2.889.626.7349.0430.770.9635.58305.5023 (106)1.897.553.7742.4526.420.9436.79805.8924 (108)0.938.332.7844.4422.220.9341.67605.6125 (94)1.067.454.2641.4915.962.1344.68605.49Average0.948.344.5347.9427.171.1136.575.60SD0.972.312.254.395.350.426.090.34Weekly data are the average of daily reported symptoms and anxiety levels.


2021 ◽  
Vol 10 (6) ◽  
pp. 1244
Author(s):  
Stinne Tranekær ◽  
Dennis Lund Hansen ◽  
Henrik Frederiksen

Background: Warm autoimmune haemolytic anaemia (wAIHA) is a haemolytic disorder, most commonly seen among adults and is classified as either primary or secondary to an underlying disease. We describe the age and sex distribution and the proportion of secondary wAIHA. Method: We retrieved 2635 published articles, screened abstracts and titles, and identified 27 articles eligible for full-text review. From these studies, we extracted data regarding number of patients, sex distribution, age at diagnosis, number of patients with secondary wAIHA, and whether the patients were diagnosed through local or referral centres. All data were weighted according to the number of included patients in each study. Results: 27 studies including a total of 4311 patients with wAIHA, of which 66% were females, were included. The median age at diagnosis was 68.7 years, however, wAIHA affected all ages. The mean proportion of secondary wAIHA was 49%, most frequently secondary to systemic lupus erythematosus. The proportions of secondary wAIHA reported from primary vs. referral centres were 35% vs. 59%, respectively. Conclusion: This review consolidates previously reported gender distribution. The higher proportion of secondary wAIHA in referral centres suggests that the most severely affected patients are disproportionally more frequent in such facilities.


2009 ◽  
Vol 62 (9-10) ◽  
pp. 461-467
Author(s):  
Ljiljana Nesic ◽  
Predrag Canovic ◽  
Zeljko Mijailovic ◽  
Jelena Djokovic

Introduction. Although well protected, brain is not resistant to infection agents. Acute infections of our nervous system appear more often in children and in persons who have medical history data about previous disorders, especially disorders of the nervous system. It is difficult to list possible risk factors which can be responsible for the appearance of infections of CNS and the resulting conditions. It is often difficult or impossible to determine what previous neural damage was (trauma, anoxic damages etc.) from those appearing during infections of CNS. All-inclusive anamnestic research reduces the possibility of approximate judgments. Material and methods. The research was based on the retrospective analysis of medical documentation of 275 patients. All patients were divided into three groups according to the final diagnosis. The first group consisted of 125 patients who were treated for acute virus encephalitis, the second group consisted of 125 patients who were treated for acute bacterial meningoencephalitis and the third group consisted of 25 patients who were treated for cerebritis. Discussion. In our studies sample, the youngest patient was 3 years old and the oldest was 87 years old. The highest number of patients with virus infection of the CNS was in the group under 25 years of age (45.6%). The highest number of patients with bacterial infections of the CNS and cerebritis was in the group of patients over 45 years of age (64%, 37%). Conclusion. Risk factors were more present in bacterial infections of the nervous system and cerebrit thanin virus infection of CNS. In virus infections of the CNS, 28% of patients had some risk factor, most often-chronic ethylism, diabetes mellitus and acquired heart diseases. In bacterial infections of the CNS, 64% of patients had some predisposed factor. The most frequent factor of risk in these patients were chronic otitis (21.6%) and craniotrauma (14.4%). In cerebritis, risk factors were present in 76% of patients and they were: sepsis (20%), chronic otitis (12%) and systemic lupus erythematosus (8%).


Lupus ◽  
2010 ◽  
Vol 19 (12) ◽  
pp. 1391-1398 ◽  
Author(s):  
Y. Avihingsanon ◽  
N. Hirankarn

Lupus nephritis is a common and severe complication of systemic lupus erythematosus. A number of patients have nephritis as a presenting feature that, in its severe form, can shortly lead to end-stage renal disease and/or death. Renal flare usually occurs a few years after the first episode and is remarkably predominant in the Asian population. Frequent monitoring for renal flare enhances early recognition and timely treatment. The mainstay therapy continues to be the prolonged use of cytotoxic/immunosuppressive drugs that have a number of undesirable effects, particularly ovarian failure and development of opportunistic infections. This review will focus on the pathogenesis and the unique genetic factors found in Asian patients with lupus nephritis. Here, we propose an appropriate management scheme for the treatment of lupus nephritis in Asian patients.


Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2667
Author(s):  
Andrea Angeletti ◽  
Stefano Volpi ◽  
Maurizio Bruschi ◽  
Francesca Lugani ◽  
Augusto Vaglio ◽  
...  

Neutrophil extracellular traps (NETs) are macromolecular structures programmed to trap circulating bacteria and viruses. The accumulation of NETs in the circulation correlates with the formation of anti-double-stranded (ds) DNA antibodies and is considered a causative factor for systemic lupus erythematosus (SLE). The digestion of DNA by DNase1 and DNases1L3 is the rate- limiting factor for NET accumulation. Mutations occurring in one of these two DNASE genes determine anti-DNA formation and are associated with severe Lupus-like syndromes and lupus nephritis (LN). A second mechanism that may lead to DNase functional impairment is the presence of circulating DNase inhibitors in patients with low DNase activity, or the generation of anti-DNase antibodies. This phenomenon has been described in a relevant number of patients with SLE and may represent an important mechanism determining autoimmunity flares. On the basis of the reviewed studies, it is tempting to suppose that the blockade or selective depletion of anti-DNase autoantibodies could represent a potential novel therapeutic approach to prevent or halt SLE and LN. In general, strategies aimed at reducing NET formation might have a similar impact on the progression of SLE and LN.


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