Low Complement Research Articles

Serum Prolactin Level in Women with Systemic Lupus Erythematosus and its Correlation with Disease Activity

Abstract Background: In the last decade, evidence supports the hypothesis that the prolactin (PRL) hormone plays an important role in systemic lupus erythematosus (SLE) clinical expression and pathogenesis. Objective: To evaluate the presence, clinical, and serological significance of elevated serum PRL in women with SLE. Materials and Methods: A case–control study included 30 women with SLE; with mean age and disease duration were 33.15 ± 6.7 and 10.9 ± 1.9, respectively, and 30 age-matched apparently healthy subjects served as controls. All patients were subjected to clinical and serological evaluation. Disease activity was measured using the SLE Disease Activity Index. Serum PRL level was estimated for all the participants. Results: Serum PRL levels were 36.2 ± 15.8 ng/ml and 8.9 ± 4.4 ng/ml in patients with SLE and controls, respectively. Malar rash, photosensitivity, and arthritis were associated with elevated serum PRL. Positive antinuclear antibodies ANA and low complements were associated with a high serum PRL level. In addition, 18 (85.7%) patients with high disease activity have hyperprolactinemia, while only 3 (14.3%) patients with high disease activity have a normal range of serum PRL levels. Conclusion: SLE patients were associated with higher serum PRL levels than the control group. There was a significant relationship between serological status and hypocomplementemia with high serum PRL levels. In addition, there was a significant relationship between active disease and hyperprolactinemia.

B cell polygenic risk scores associate with anti-dsDNA antibodies and nephritis in systemic lupus erythematosus

ObjectiveB cell function and autoantibodies are important in SLE pathogenesis. In this work, we aimed to investigate the impact of cumulative SLE B cell genetics on SLE subphenotype and autoantibody...

OA14 The role of anifrolumab in treating life threatening systemic lupus erythematosus with severe mucocutaneous involvement

OA14 The role of anifrolumab in treating life threatening systemic lupus erythematosus with severe mucocutaneous involvement

P10 Collapse, confusion and acute kidney injury presenting in the context of bullous skin disease in a young male patient

P10 Collapse, confusion and acute kidney injury presenting in the context of bullous skin disease in a young male patient

Non-criteria autoantibodies in antiphospholipid syndrome may be associated with underlying disease activity.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by persistent antiphospholipid antibodies (aPLs) with arterial and venous thrombosis and/or pregnancy morbidity. In recent years, several studies have highlighted the potential role of non-criteria aPL in diagnosing APS patients. This study aimed to determine the association of the presence of non-criteria aPL antibodies to the clinical and laboratory features of patients with a diagnosis of APS. Eighty patients diagnosed with APS and under observation in the rheumatology clinic of Ankara City Hospital were assessed. Patient demographic and clinical features were meticulously recorded. Non-criteria antibodies tested in our center included antiphosphatidylserine IgA, antiphosphatidylserine IgM, beta 2 glycoprotein IgA, anti-cardiolipin IgA, antiphospholipid antibody IgG, and antiphospholipid antibody IgM. Antibodies from patients who were tested for at least one non-criteria antibody were documented. Out of 80 patients, 55 (68.8%) were tested for at least one non-criteria antibody, and 29 of those patients (52.7%) tested positive for at least one non-criteria antibody. The antiphospholipid antibody IgM and the beta 2 glycoprotein IgA were the most commonly tested non-criteria antibodies. Patients with non-criteria antibody positivity had a higher frequency of Ds DNA positivity and low complement (62.0% vs. 35.0%, p = 0.042; 69.0% vs. 38.0%, p = 0.023), respectively. In addition, positivity for anti-cardiolipin IgG and b2 glycoprotein IgG was significantly higher in the group positive for non-criteria antibodies (79% vs. 31%, p ≤ 0.001; 72.0% vs. 19%, p ≤ 0.001). There was no significant difference between the clinical features of patients with at least one positivity for non-criteria antibodies and those without. Systemic lupus erythematosus (SLE) is the most commonly associated disease with APS, being present in approximately 35% of cases[1]. Since the majority of the patient group in our study had APS that was secondary to SLE, non-criteria antibody positivity may be linked to the immunological activity of SLE. Large multicenter studies are necessary to investigate the clinical significance of isolated/combined positivity for criterion/non-criteria aPLs.

Systemic lupus erythematosus with high disease activity identification based on machine learning.

Clinical evaluation of systemic lupus erythematosus (SLE) disease activity is limited and inconsistent, and high disease activity significantly, seriously impacts on SLE patients. This study aims to generate a machine learning model to identify SLE patients with high disease activity. A total of 1014 SLE patients with low disease activity and 453 SLE patients with high disease activity were included. A total of 94 clinical, laboratory data and 17 meteorological indicators were collected. After data preprocessing, we use mutual information and multisurf to evaluate and select the importance of features. The selected features are used for machine learning modeling. Performance of the model is evaluated and verified by a series of binary classification indicators. We screened out hematuria, proteinuria, pyuria, low complement, precipitation, sunlight and other features for model construction by integrated feature selection. After hyperparameter optimization, the LGB has the best performance (ROC: AUC = 0.930; PRC: AUC = 0.911, APS = 0.913; balance accuracy: 0.856), and the worst is the naive bayes (ROC: AUC = 0.849; PRC: AUC = 0.719, APS = 0.714; balance accuracy: 0.705). Finally, the selection of features has good consistency in the composite feature importance bar plot. We identify SLE patients with high disease activity by a simple machine learning pipeline, especially the LGB model based on the characteristics of proteinuria, hematuria, pyuria and other feathers screened out by collective feature selection.

Market development of Islamic banking in Pakistan and its economic impact

Purpose This study aims to examine the dynamics of the market development of Islamic banking in Pakistan. This study investigates how shocks to the economy in the form of changes in benchmark rate and exchange rate and internal factors such as efficiency, profitability and asset quality affect the development of Islamic banking. The study also evaluates the impact of Islamic banking on the real economy in the macro perspective and society at large in terms of inclusiveness, competitiveness and fairness. Design/methodology/approach Autoregressive distributed lagged model method is used for analysing the short-run and long-run determinants of market development of Islamic banking and the economic impact of Islamic banking on the real economy. Findings Profitability and exchange rate have a positive effect on market development of Islamic banking while higher inefficiency and interbank rate have a negative effect. On the other hand, financing intensity and profitability in Islamic banking positively affect the large-scale manufacturing sector. Practical implications Stable profits, high asset quality, efficiency and rising import demand with low policy rate environment complement Islamic banking growth. Moreover, the economic assessment shows that Islamic banks have been able to achieve the financial inclusion of those who want to avoid Riba, but they need concerted efforts to improve competitiveness and distinction with regard to distributional impact. Originality/value To the best of the authors’ knowledge, this is the first study in Pakistan to evaluate determinants of market development of Islamic banking taking 16-year quarterly data and assessing the economic effects of Islamic banking on inclusiveness, competitiveness and fairness.

Risk Factors for Skin Infection in Patients with Systemic Lupus Erythematosus (SLE)

Background: Systematic lupus erythematosus (SLE) is an autoimmune chronic disease that sometimes leads to serious life-threatening condition. The occurrence of SLE was about 5 million worldwide by 2022. The overall frequency of SLE across Asian countries ranged from 0.9 to 3.1 per 100,000. Infection is one of the grave condition in SLE patients. This study intended to evaluate risk factors for skin infections in patients with systematic lupus erythematosus. Material & Methods: This observational prospective study was carried out in the Department of Rheumatology, BSMMU, Dhaka, Bangladesh from November 2014 to April 2016. A total of 131 patients with systematic lupus erythematosus were enrolled in this study as study subjects following the inclusive criteria. Data were collected using the predesigned semi-structured questionnaire. Proper written consent was taken from all the participants, before recruiting. Completed data forms were reviewed, edited, and processed for computer data entry. The data analysis was performed using Statistical Package for the Social Sciences (SPSS) Version 25.0. Univariate and multivariate analyses were performed to identify the predictive of infection in patients with systemic lupus erythematosus (SLE) where P<0.05 was considered as the level of significance with 95%CI. Results: Among the total study population (N=131), skin infections were found in 27% of cases (n=35) whereas 73% of cases were non-infected (n=96). In the infected group, the mean age of the respondents was 28.2±8.7 years. Taeniasis was the most common skin infection (15, 42.9%), and herpes infection was found in 12 patients (34.3%). Higher SELENA SLEDAI scores were more frequent in skin infected group than that in the non-infected group. Skin infections were significantly higher among the participants who used I.V. cyclophosphamide. In skin infected group, immunosuppressive drugs were used significantly in higher frequency (94.3% versus 24.0%) than in the non-infected group. In the multivariate analysis, higher disease activity (SELENA-SLEDAI score >3, (P=0.049) (OR=21.44), higher daily doses of prednisolone intake (>10mg/day, P=0.046) (OR=16.69), low serum C3/C4 (P=0.004) (OR=147.82) and use of any immunosuppressive drugs either in present or previously (P value= 0.042) (OR=22.58) were found as significant risk factors. Conclusion: In this study, taeniasis and herpes infections were found as the most common skin infections among patients with systemic lupus erythematosus (SLE). Higher disease activity, a higher dose of prednisolone, use of any immunosuppressive therapy either present or past and low complement level were the risk factors for skin infections.

Low levels of complement factor C3 at diagnosis can predict outcome in antineutrophil antibody associated vasculitis.

Experimental data support the involvement of complement in the pathogenesis of antineutrophil antibody associated vasculitis, and clinical studies describe a more severe disease phenotype in patients with antineutrophil antibody associated vasculitis and complement activation. In the present study, we looked for an association between circulating serum complement factor 3 levels at diagnosis and outcomes. One hundred sixty-four patients with antineutrophil antibody associated vasculitis who underwent kidney biopsy at our center during the last 15years were retrospectively reviewed. Patients were categorized according to their serum complement factor 3 level at diagnosis. Patient and renal survival were compared between those above and below the median serum complement factor 3 at diagnosis. During the first year, 6 patients died and 53 reached end-stage renal disease. Death or end-stage renal disease at one-year were significantly more common in the low serum complement factor 3 group (44 vs. 29%, p = 0.037). In the multivariable analysis, serum complement factor 3 was the strongest negative outcomepredictor (HR, 95%CI 0.118, (0.021-0.670)). The lower the serum complement factor 3 level at baseline, the higher the risk of dialysis and death. The risk was particularly high for both endpoints if the serum complement factor 3 concentration was below 0.9g/l at baseline. Complement activation at diagnosis may identify a distinct subgroup of patients with antineutrophil antibody associated vasculitis and higher risk for poor outcomes. However, it remains to be proven whether inhibition of serum complement factor 3 is beneficial and safein the clinical setting.

Comparison of the Effectiveness and Safety of Mycophenolate Mofetil and Cyclophosphamide in Lupus Nephritis: Evidence from a Real-World Study.

Both mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC) have been recommended in the induction therapy of lupus nephritis (LN) for years; nevertheless, their effectiveness and safety in a real-world setting are extremely lacking. Therefore, we decided to conduct this real-world study. A total of 195 Chinese patients with LN who were initially treated with MMF (n = 98), or intravenous CYC (n = 97) as induction therapy were enrolled. All of the patients were followed up to 12months. Complete renal remission (CRR) was defined as 24-h urinary protein (24h-UTP) < 0.5g, and partial renal remission (PRR) was defined as ≥ 50% reduction in 24h-UTP to the subnephrotic level, however > 0.5g, both with a change of serum creatinine (SCr) within 10% from baseline. The proportions of CRR, PRR, and total renal remission (TRR), as well as adverse events, were compared by Chi-square test and Kaplan-Meier analysis (log-rank test). Inverse probability of treatment weighting (IPTW) was used for propensity score matching and multivariable logistic regression analyses were employed. The cumulative proportion of TRR in 6months (79.4 vs. 63.8%, p = 0.026) and CRR in 12months (72.8 vs. 57.6%, p = 0.049) in MMF group were significantly higher than CYC group, and the above conclusions were further confirmed by IPTW. The proportions of PRR, CRR, and TRR at other time points were equivalent between two groups. Further subgroup analysis in 111 patients with biopsy-proven III-V LN also showed a significantly higher proportion of TRR at 6months in the MMF group than in the CYC group (78.3 vs. 56.9%, p = 0.026). In the Kaplan-Meier analysis and after IPTW, the MMF group showed better TRR and CRR responses than CYC group in 12months. Multivariable logistic regression analyses revealed that MMF use was the only predictor of CRR (HR 2.12, 95% CI 1.90-4.09, p = 0.026), while low complement level was also a predictor, albeit risk was reduced (HR 0.38, 95% CI 0.17-0.86, p = 0.019). Moreover, compared to the CYC group, MMF group patients were more likely to have significantly lower SCr (μmol/l) [72.5 (62.5, 86.5) vs. 79.0 (71.1, 97.5), p = 0.001] and daily dose of prednisone (mg/day) (15.7 ± 5.2 vs. 18.6 ± 11.3, p = 0.022) at 6months; lower 24h-UTP (g) [0.1 (0.1, 0.3) vs. 0.2 (0.1, 0.9), p = 0.005] and daily dose of prednisone (mg/day) (9.6 ± 3.3 vs. 11.2 ± 5.5, p = 0.023) at 12months. Infection was the most common adverse event. Pneumonia and gastrointestinal discomfort were more frequently observed in the CYC group. Real-world data are a key component of the evidence supporting the effectiveness of drugs and are of interest to all stakeholders. Our comparative study demonstrated the effectiveness of MMF in LN induction therapy was at least equivalent to intravenous CYC, with superior tolerance.

Prognostic value of complement serum C3 level and glomerular C3 deposits in anti-glomerular basement membrane disease.

Activation of the complement system is involved in the pathogenesis of anti-glomerular basement membrane (anti-GBM) disease. Glomerular deposits of complement 3 (C3) are often detected on kidney biopsies. The primary objective of this study was to analyze the prognostic value of the serum C3 level and the presence of C3 glomerular deposits in patients with anti-GBM disease. We conducted a retrospective cohort study of 150 single-positive patients with anti-GBM disease diagnosed between 1997 and 2017. Patients were categorized according to the serum C3 level (forming a low C3 (C3<1.23 g/L) and a high C3 (C3≥1.23 g/L) groups) and positivity for C3 glomerular staining (forming the C3+ and C3- groups). The main outcomes were kidney survival and patient survival. Of the 150 patients included, 89 (65%) were men. The median [interquartile range (IQR)] age was 45 [26-64]. At diagnosis, kidney involvement was characterized by a median [IQR] peak serum creatinine (SCr) level of 578 [298-977] µmol/L, and 106 (71%) patients required dialysis. Patients in the low C3 group (72 patients) had more severe kidney disease at presentation, as characterized by higher prevalences of oligoanuria, peak SCr ≥500 µmol/L (69%, vs. 53% in the high C3 group; p=0.03), nephrotic syndrome (42%, vs. 24%, respectively; p=0.02) and fibrous forms on the kidney biopsy (21%, vs. 8%, respectively; p=0.04). Similarly, we observed a negative association between the presence of C3 glomerular deposits (in 52 (41%) patients) and the prevalence of cellular forms (83%, vs. 58% in the C3- group; p=0.003) and acute tubulo-interstitial lesions (60%, vs. 36% in the C3- group; p=0.007). When considering patients not on dialysis at diagnosis, the kidney survival rate at 12 months was poorer in the C3+ group (50% [25-76], vs. 91% [78-100] in the C3- group; p=0.01), with a hazard ratio [95% confidence interval] of 5.71 [1.13-28.85] (p=0.04, after adjusting for SCr). In patients with anti-GBM disease, a low serum C3 level and the presence of C3 glomerular deposits were associated with more severe disease and histological kidney involvement at diagnosis. In patients not on dialysis at diagnosis, the presence of C3 deposits was associated with worse kidney survival.

Early osteoimmunomodulation by mucin hydrogels augments the healing and revascularization of rat critical-size calvarial bone defects.

The design principle of osteogenic bone grafts has shifted from immunological inertness to limiting foreign body response to combined osteoimmunomodulatory activity to promote high-quality endogenous bone regeneration. Recently developed immunomodulatory mucin hydrogels have been shown to elicit very low complement activation and suppress macrophage release and activation after implantation in vivo. However, their immunoregulatory activity has not yet been studied in the context of tissue repair. Herein, we synthesized mucin-monetite composite materials and investigated their early osteoimmunomodulation using a critical-size rat bone defect model. We demonstrated that the composites can polarize macrophages towards the M2 phenotype at weeks 1 and 2. The early osteoimmunomodulation enhanced early osteogenesis and angiogenesis and ultimately promoted fracture healing and engraftment (revascularization of the host vasculature) at weeks 6 and 12. Overall, we demonstrated the applicability of mucin-based immunomodulatory biomaterials to enhance tissue repair in tissue engineering and regenerative medicine.

A case of hypocomplementemic urticarial vasculitis syndrome complicated by eosinophilic pneumonia: a case report and review of the literature.

The primary symptom of urticarial vasculitis (UV), which is a histopathological leukocytoclastic vasculitis disease, is an eruption that resembles urticaria. Other organs may also experience accompanying symptoms. Lung lesions with UV are mostly obstructive pulmonary disease with smoking. However, the coexistence of eosinophilic pneumonia (EP) and complicated UV remains unclear. We report a man in his 70s with chronic obstructive pulmonary disease who attended our department with ring-shaped erythema, marginal edema, and pigmentation. Additionally, a skin histological analysis showed nuclear dust and perivascular neutrophil infiltration, while a blood sample showed a decrease in C3 and C1q concentrations. Administration of prednisone temporarily improved the eruption. However, he developed a cough and a new UV eruption 1 year later. Computed tomography revealed infiltration in the right upper lobe of the lungs, and a blood sample showed a high eosinophil count. He was finally diagnosed with hypocomplementemic urticarial vasculitis syndrome and idiopathic chronic EP. A previous study showed that serum C1q concentrations in patients with EP were lower when this disease was active. Whether a decline in C1q concentrations can cause EP is unclear. However, our case is unique owing to the co-onset of EP with low complement concentrations and recurrence of UV.

Systemic lupus erythematosus with Fahr’s syndrome: A case report with review of literature

Systemic lupus erythematosus (SLE) is a multisystem disease with autoimmune etiology. The neurological manifestations of lupus are diverse. We introduce a case of a 40-year-old male who presented with constitutional symptoms like low-grade fever, myalgia, and easy fatigability for one month. On examination, he had icterus, hepatosplenomegaly, and spasticity. Lab tests were suggestive of autoimmune hemolytic anemia with ANA positivity and low complements. Diagnosis of SLE was certain. CT brain showed bilateral symmetrical dense radial and punctate calcifications involving bilateral cerebral and cerebellar hemispheres suggestive of Fahr’s syndrome.

Multiple autoimmune syndrome: Clinical, immunological and genotypic characterization

IntroductionThe existence of subphenotypes common to several autoimmune diseases (AIDs) suggests a shared physiopathology - autoimmune tautology. Multiple Autoimmune Syndrome (MAS) - the coexistence of three or more AIDs in one person-, best illustrates that polyautoimmunity is more than a coincidence. ObjectivesCharacterize and compare the monoautoimmune and MAS patients. Understand if clustering of AIDs leads to differences in disease severity, autoantibodies expression or genetic polymorphisms that could be markers for polyautoimmunity. MethodsCurrently adult patients were selected from unit cohort. MAS was assumed when ≥3 AIDs were present. 343 patients were included after exclusion criteria: having two AIDs or undetermined diagnosis. Clinical and immunological data were collected from medical files. HLA-DRB1 was genotyped by PCR-SSP methodology and PTPN22(rs2476601) polymorphisms by TaqMan Real Time PCR. Data were analysed using Chi-Square, Fisher's exact tests and logistic regression. Odds ratios (OR) and 95% confidence intervals were calculated. ResultsIn comparison with control population: Elevated frequenciesHLA-DRB1*03 in study cohort (OR=3.68,p<0.001) and in monoautoimmune SLE (OR=2.79,p<0.001) and SjS (OR=8.27,p<0.001); HLA-DRB1*15 in monoautoimmune SjS (OR=2.39,p = 0.011); HLA-DRB1*16 in MAS SLE (OR=2.67,p = 0.031); PTPN22_T in all groups except monoautoimmune SjS and triple positive systemic MAS. Diminished frequenciesHLA-DRB1*11 in study cohort (OR=0.57,p = 0.013), in MAS SLE (OR=0.39,p = 0.031) and monoautoimmune SjS (OR=0.10,p = 0.005); HLA-DRB1*13 in study cohort (OR=0.52,p = 0.001) and in monoautoimmune SLE (OR=0.53,p = 0.009) and SjS (OR=0.38,p = 0.031); HLA-DRB1*14 in study cohort (OR=0.32,p = 0.013) and monoautoimmune SLE (OR=0.21,p = 0.021); SLE group: HLA-DRB1*07 frequency was higher in monoautoimmune patients (OR=0.43,p = 0.023). MAS patients had significantly more NPSLE (OR=2.99,p<0.001), subacute cutaneous lesions (OR=2.30,p = 0.037), muscle&tendon (OR=2.00,p = 0.045), and haematological (OR=3.18,p = 0.006) involvement and Raynaud's (OR=2.94,p<0.001). SjS group: MAS patients had more frequently cryoglobulins (OR=2.96,p = 0.030), low complement (OR=2.43,p = 0.030) and Raynaud's (OR=4.38,p<0.001); monoautoimmune patients had more parotid enlargement (OR=0.12,p<0.001). APS group: MAS patients had more non-thrombotic manifestations (OR=4.69,p = 0.020) and Raynaud's (OR=9.12,p<0.001). Triple positive systemic MAS (SLE+SjS+APS) had more frequently severe kidney involvement (OR=11.67,p = 0.021) and CNS thrombosis (OR=4.44,p = 0.009). Anti-U1RNP increased frequency was transversally attributable to MAS. ConclusionsThe coexistence of AIDs contributes to a more severe disease course. We confirmed previously established genetic risk and protection factors and suggest a new protective one - HLA-DRB1*14. HLA-DRB1*07 and anti-U1RNP could be markers for mono and polyautoimmunity, respectively; HLA-DRB1*13 could be a predictor for vascular risk in patients with multiple AIDs. PTPN22(rs2476601) polymorphism could be associated with less severe disease.

Unusual presentation and rare association of pediatric lupus

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune inflammatory disorder with diverse clinical manifestations which can lead to significant morbidity and mortality. Children and adolescents represent 15% to 20% of all patients with SLE. Childhood onset SLE is a rare disease with a prevalence of 3.5 to 8.8 per one lakh children. Localized or generalized lymphadenopathy may be an uncommon presenting feature of SLE. None of the classification criteria for SLE include lymphadenopathy as a criterion including the latest 2019 American college of rheumatology (ACR) / European league against rheumatism (EULAR) criteria. Nine-year-old female child presented with history of swelling on both sides of neck associated with fever and easy fatiguability for 2 months. Clinical examination revealed significant bilateral cervical and axillary lymph nodes with hepatomegaly. Excision biopsy of lymph node was suggestive of Kikuchi Fujimoto disease (KFD). As rare association of KFD with SLE is well described in literature, despite negative clinical features and laboratory findings of SLE, including an initial negative ANA IF test, we did a repeat ANA IF, complement (C3) level and dsDNA testing, all of which turned out to be positive, confirming the diagnosis of SLE. The child was started on hydroxychloroquine and oral steroids with dramatic response. During steroid tapering she developed a flare needing the addition of azathioprine. Currently she is in remission and is under follow up. Although rare, lupus lymphadenopathy may be a presenting feature of SLE. This can even antecede the diagnosis of SLE by many years, when the presence of auto antibodies or low complement levels are not detected and are associated with higher disease activity. This emphasizes the importance of high index of suspicion of SLE in cases of lymphadenopathy, enabling early diagnosis and management which is essential for preventing morbidity and mortality.

Lupus and antiphospholipid syndrome diagnosis in a young female presenting with multiple non-specific symptoms

A female in her 30s with no known past medical conditions presented to North Shore University Hospital with three weeks of intermittent fevers, fatigue, and malaise. She also reports generalized body pain, myalgias, ear pain, throat pain, and joint pain. She denies rash. She also reports nausea, vomiting, and diarrhea and a 10-pound weight loss in one week. She had a miscarriage at 16 weeks of gestation. She met systemic inflammatory syndrome criteria on admission as she was febrile to 102.9 Fahrenheit, tachycardic to 120 beats per minute, tachypneic to 22 breaths/minute, and had leukopenia with white blood cell count of 2,470 per cubic milliliter. Labs were significant for pancytopenia, elevated transaminases, low C3 complement level, double stranded DNA > 1000 IU/mL, anti-nuclear factor positive 1:1280, and positive antiphospholipid serology. She was treated with steroids and hydroxychloroquine and was started on warfarin.

#5894 HYPOCOMPLEMENTEMIA AT DIAGNOSIS OF ANCA-ASSOCIATED VASCULITIS IS ASSOCIATED WITH SEVERITY AND OUTCOMES

Abstract Background and Aims A relationship between antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and complement has been shown, and complement has an important role in the pathogenesis of AAV [1]. Low serum complement levels (sC3) at diagnosis of AAV has been previously described although clinical characteristics and outcomes of AAV with hypocomplementemia still remain unclear [2]. The aim of this study was to investigate what proportion of patients with AAV have low sC3 at diagnosis, and whether they have different clinical and histological features or experience different outcomes compared to patients with normal sC3. Method A total of 93 patients with AAV diagnose (81,3% Anti-MPO and 18,7% anti-PR3) were included in the study from 2000-2022. 12% of them had sC3 values below limit of normal range (i.e., &amp;lt;90 mg/dl). Patients were categorized according to sC3 levels into 2 groups, hypocomplementemic (G1; mean C3: 73.1mg/dl), and normocomplementemic (G2; mean C3: 128.3mg/dl). Histological patterns were based on the Berden score and correlated with clinical features. Main outcomes of interest included severity of acute kidney injury at diagnose (AKI), histopathological patterns, end-stage kidney disease (ESKD) and death in the long term. Results No differences were identified in terms of demographics (age, gender, induction treatment). sC3 levels and serum creatinine were statistically associated (r2:-0.40; p&amp;lt;0.001). Patients with low sC3 had more severe renal involvement, at diagnose (G1: sCr 7.6mg/dl vs sCr 3.8mg/dl, p&amp;lt;0.001) without differences in ANCA levels and they were more likely to require acute dialysis around the initial diagnosis (p &amp;lt; 0.01). There were significant differences in sCr levels at diagnose (p&amp;lt;0.001) related to Berden score without differences in sC3 levels (Focal, n = 8 (8.6%), sCr 2.5 mg/dl, sC3 121.1 mg/dl; Crescentic, n = 23 (24.7%), sCr 6.41mg/dl, sC3 119.3 mg/dl; Mixed n = 16 (17.2%), sCr 3.6mg/dl, sC3 118.5 mg/dl; Sclerotic, n = 14 (15.1%) sCr 3.0 C3 129.1mg/dl). 55.5% of G1 patients deceased compared to 28% of G2. Lower sC3 levels (G1) were associated with mortality (log-rank 4.1; p&amp;lt;0.05) and composite outcome of ESKD or death (log-rank 5.9; p&amp;lt;0.05) compared G2 patients. Conclusion Hypocomplementemia in AAV at the disease onset was a risk factor for the serious organ damage, and a life prognostic factor. Low C3 levels at diagnosis of AAV is emerging as a predictor of renal outcomes and it is thus very important to pay attention to them. Despite that histologic patterns of the Berden classification were related to the severity of AKI at presentation there was no statistical correlation with sC3 levels. We recommend to pay attention to the levels of complement at the diagnosis of AAV.

#2691 GLOMERULAR LESIONS IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME

Abstract Background and Aims Antiphospholipid syndrome (APS) is a complex autoimmune systemic disease, characterized by the presence of circulating antibodies directed against anionic phospholipids and the protein bound to them (aPL), leading to recurrent thrombosis and/or obstetrical complications. Renal manifestation of antiphospholipid syndrome conform a wide spectrum of disease renal syndrome. APS nephropathy (APSN) is considered a renal small-vessels vasculopathy, that can present acutely or chronically. The aim of the study is to identify glomerular lesions in patients with APSN. Method We studied retrospectively 114 patients (51 male, 63 female; age between 19 and 58 years; duration of follow-up was between 2 and 16 years) fulfilling classification criteria for APS. Renal and extra-renal symptoms were analyzed. None of the patients developed SLE in follow up. 18 patients with evidence of renal involvement underwent renal biopsy. All cases had proteinuria and five of them presented nephrotic syndrome. Results Of 18 patients with kidney biopsy, 8 (44,44%) were male and 10 (55,56%) - female. Four of patients with renal biopsy had membranous glomerulonephritis, two had diffuse proliferative glomerulonephritis, 2 - mesangial C3 nephropathy, 2 - minimal change disease, 1- focal segmental glomerulosclerosis, the other seven had classic pathologic findings consistent with APSN. Chronic lesions with fibrous intimal hyperplasia being the most common. Thrombotic microangiopathy (TMA) in glomeruli was characterized by fibrin thrombi without inflammatory cells or immune complexes. Double contour of the glomerular basement membrane was associated with mesangiolysis and endothelial cell swelling in 5 patients with APSN. Electron microscopy confirmed subendothelial edema. Segmental glomerulosclerosis was observed in 4 patients. Tubulointerstitium was injured with interstitial fibrosis and tubular atrophy. Patients with APS and renal involvement were older (p&amp;lt;0,05), had LA positive test (p&amp;lt;0,005) and low complement levels (p&amp;lt;0,05). Hypertension is present in all cases with APSN, reduced glomerular filtration rate – in 4. All cases had proteinuria and five of them presented with nephrotic syndrome. Microscopic hematuria is observed in 4 patients. The treatment of APSN includes standard anticoagulant treatment for APS, inhibitors of the angiotensin system in patients with hypertension and proteinuria, steroids, intravenous immunoglobulin, cyclophosphamide and azathioprine. Conclusion Of 18 patients with kidney biopsy, 8 (44,44%) were male and 10 (55,56%) - female. Four of patients with renal biopsy had membranous glomerulonephritis, two had diffuse proliferative glomerulonephritis, 2 - mesangial C3 nephropathy, 2 - minimal change disease, 1- focal segmental glomerulosclerosis, the other seven had classic pathologic findings consistent with APSN. Chronic lesions with fibrous intimal hyperplasia being the most common. Thrombotic microangiopathy (TMA) in glomeruli was characterized by fibrin thrombi without inflammatory cells or immune complexes. Double contour of the glomerular basement membrane was associated with mesangiolysis and endothelial cell swelling in 5 patients with APSN. Electron microscopy confirmed subendothelial edema. Segmental glomerulosclerosis was observed in 4 patients. Tubulointerstitium was injured with interstitial fibrosis and tubular atrophy. Patients with APS and renal involvement were older (p&amp;lt;0,05), had LA positive test (p&amp;lt;0,005) and low complement levels (p&amp;lt;0,05). Hypertension is present in all cases with APSN, reduced glomerular filtration rate – in 4. All cases had proteinuria and five of them presented with nephrotic syndrome. Microscopic hematuria is observed in 4 patients. The treatment of APSN includes standard anticoagulant treatment for APS, inhibitors of the angiotensin system in patients with hypertension and proteinuria, steroids, intravenous immunoglobulin, cyclophosphamide and azathioprine.

Lysine-Sarcosine PiPo Functionalized Surface with Excellent Hemocompatibility.

Polysarcosine (PSar) is an electrically neutral and excellently hydrophilic polypeptoid showing limited interaction with proteins and cells, which possesses better biocompatibility compared with polyethylene glycol. However, the immobilization of PSar is difficult due to the high water solubility. Herein, lysine-sarcosine PiPo, which was the random copolymer of lysine and sarcosine (PLS), was synthesized via a phosgene-free and water-tolerable polymerization of N-phenyloxycarbonyl-amino acids for the first time. PLS was immobilized by tannic acid (TA) on the polysulfone (PSf) membrane for a short time to obtain a neutral surface. The modified membrane showed improved hydrophilicity, decreased protein adsorption, and low cytotoxicity. Moreover, barely any hemolysis, no platelet adhesion, prolonged clotting time, and low complement activation further suggested good hemocompatibility. In order to improve the antifouling ability of the membrane under pressure, the neutral surface was oxidized by sodium periodate, which accelerated the chemical reaction between amino groups in PLS and phenolic hydroxyl groups in TA. Meanwhile, carboxyl groups generated due to the decomposition of TA and a negatively charged surface were obtained. While maintaining the good properties of the unoxidized one, the hydrophilicity of the oxidized membrane was improved and the clotting time was further prolonged. Besides, the filtration recovery of the oxidized membrane was improved remarkably. This approach of rapid immobilization of PSar has great potential for applications in the biomedical area, especially for blood-contacting materials.