Low complement items play different roles on the classification performance of SLICC-2012, EULAR/ACR-2019, and SLERPI

Background and Aims A full-house pattern at immunofluorescence (IF) in kidney biopsies is usually associated with Lupus Nephritis (LN). However, it can be also secondary to other causes, such as infections, or it can idiopathic, without a defined origin. Idiopathic Full House non-lupus Nephropathy (iFH-N) represents a rare entity previously identified in small cohorts of patients, with different clinical features and outcomes. A limited number of the described cases developed overt systemic lupus erythematosus (SLE) during follow up, while renal outcome varied across different studies. A retrospective observational study aimed at evaluating clinical presentation and outcomes of patients with iFH-N in a Tertiary Center has been performed. Long-term renal function and development of overt SLE have been considered as main outcomes of the study. Method All native kidney biopsies performed from January 2012 to December 2022 in our Institution were considered. Full-house pattern was defined as simultaneous positivity for IgG, IgM, IgA, C3 and C1q staining at IF. Inclusion criteria were: age ≥18, full-house pattern at kidney biopsy, patients not meeting criteria for SLE diagnosis according to American College of Rheumatology (ACR) 1997 classification or Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria. Exclusion criteria: diagnosis of SLE, secondary causes of full-house pattern at kidney biopsy. We considered histological, clinical and laboratory features, performed therapies, renal function and SLE development during follow up. Results In the considered period, 2110 patients underwent a native kidney biopsy at our Institution. Of these, 91 patients had a histological finding of full-house nephropathy and were initially included for further evaluation. Of the 91 patients, 84 had received a diagnosis of SLE and were excluded, while 7 did not meet the criteria for a diagnosis of SLE. Two of these 7 were further excluded, having a full house pattern secondary to other conditions. Five patients were finally labelled as iFH-N. At kidney biopsy, all 5 included subjects had a Membranous Nephropathy, with extracapillary proliferation in 2 cases. They were all females, 4 Caucasians (80%), 1 Black (20%). At presentation, mean age was 28.2 years (range 21–40). All had impairment of kidney function, 2 of 5 had a full-blown nephrotic syndrome, 3 of 5 a nephrotic range proteinuria. Mean serum creatinine was 2.1 mg/dl (SD± 0.47), mean eGFR 35.2 ml/min/1.73 m2 (SD ±11), mean proteinuria 7.1 gr/24 h (SD ±3.3). Antinuclear antibodies (ANA) were negative in 4 of 5 patients; anti-dsDNA, anti-extractable nuclear antigens (ENAs) and antiphospholipid antibodies were negative in all subjects; slightly low C3 was present in 3 of 5 subjects. All patients received immunosuppressive therapy, including high dose intravenous (iv) steroids in association with cyclophosphamide (CYC) or mycophenolate mofetil, or Intensified B Cell Depletion Protocol (i.e. iv steroids + CYC and Rituximab). Mean follow-up from the time of kidney biopsy was 7.4 year (SD ± 2.4) (range 3–10 years). During follow up, 4 patients (80%) developed end stage renal disease (ESRD) needing renal replacement therapy, 3 of them within 24 months after presentation. The two patients with crescents had a severe prognosis, starting dialysis within 10 months after presentation. The fifth patient developed chronic kidney disease stage 4. One patient formally developed an ACR negative, SLICC positive SLE two years after presentation, with new positivity for ANA and anti-dsDNA antibodies at high titer and low C3, in addition to renal involvement. Conclusion All patients with iFH-N had similar presentation, being all young females, with a Membranous Nephropathy, nephrotic proteinuria and impairment of kidney function. They all had an aggressive form of kidney disease, refractory to different regimens of immunosuppression and with poor long-term renal outcome. Only one case developed SLE on the long term, although without systemic signs. The relationship between idiopathic full-house nephropathy and SLE remains controversial.

SAT0430 Application and Validation of New Classification Criteria (Slicc) for Lupus Erythematosus in the Real Life of a Tertiary Referal Hospital in Brazil

Background and Aims ANCA-associated vasculitis (AAV) is a condition that remains poorly understood. Recent data suggest the existence of a complement alternative pathway activation in the pathogenesis of this disease. And recent studies have correlated low complement levels to unfavourable outcomes. Our study aimed to determine whether low serum C3 levels could be used to estimate the severity of AAV and predict renal survival. Method Our study enrolled 26 patients diagnosed with AAV between January 2013 and January 2023. C3 levels were assessed at the time of diagnosis, and patients were categorized into two groups: those with low serum C3 levels and those with normal serum C3 levels (0.9–1.8 g/l). We examined the correlation between serum C3 levels and the severity of AAV at the time of diagnosis, as well as renal survival. Results The average age at diagnosis was 52.5 years, with 15 male patients (57.69%). All patients had kidney involvement, 30% of patients had respiratory symptoms (mostly due to diffuse alveolar hemorrhage) 42% had Ear Nose Throat system involvement 15% had nervous symptoms and 38% had skin signs. The mean Birmingham Vasculitis Activity Score (BVAS) at presentation was 20, and the average serum creatinine level was 360 µmol/l. The mean serum C3 and C4 levels were 108.3 and 24.5 mg/dL, respectively. Forty-two percent of the patients (eleven patients) had a low serum C3 level at presentation. Low C3 level was significantly correlated with poor renal survival (p: 0.031) and relapse after 6 months of immunosuppressive treatment (p: 0.02). Furthermore, remission at 6 months was significantly more frequent in patients with normal C3 levels. Conclusion The assessment of C3 level in AAV can be a valuable tool to predict the disease severity. Hypocomplementemia can predict worse renal outcome. This phenotype may confer a poor response to usual immunosuppressive approaches. Corresponding patients may greatly benefit from complement-targeting therapy.

Complement activation and low complement levels are common in systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL) are found in about 30-40% of patients with SLE. This study aimed to investigate the association between aPL and complement levels in patients with SLE. Serum samples were collected from 269 patients with SLE enrolled in the Norwegian Systemic Connective Tissue and Vasculitis Registry (NOSVAR) during 2003-2009, and from 353 controls. All samples were analysed for anti-β2 glycoprotein 1 (anti-β2GP1) and anticardiolipin antibodies (aCL), C-reactive protein (CRP) and complement components C3 and C4. Median CRP level was significantly higher in cases than in controls (2.06 versus 0.90mg/l; P<0.0001). No significant difference in CRP was found between SLE patients with or without aPL (2.09 versus 1.89; P=0.665). Median C3 levels were similar in cases (1.03g/l) and controls (1.00g/l), whereas median C4 levels were 0.16g/l in cases versus. 0.19 in controls (P<0.0001). However, aPL-positive SLE patients had significantly lower median C3 levels (0.92 versus. 1.07g/l; P=0.001) and C4 levels (0.11 versus 0.16g/l; P<0.0001) compared to aPL-negative patients. Lower C3 and C4 values in aPL-positive SLE patients may reflect a higher consumption of C3 and C4 due to more pronounced complement activation in aPL-positive SLE patients compared to SLE patients without aPL.

BackgroundWomen with systemic lupus erythematosus (SLE) are known to have more difficulty in achieving a successful pregnancy than healthy women. They have a higher risk for adverse pregnancy outcomes (APOs)...

The clinical and serologic heterogeneity of systemic lupus erythematosus (SLE) presents challenges for diagnosis, particularly in the earliest stages of the disease when there are insufficient signs to make a reliable diagnosis. To make a comparative assessment of sensitivity and specificity of various classification criteria of SLE on a cohort of patients of Nasonova Research Institute of Rheumatology. A total of 252 patients were included in the study; 152 (60%) of 252 patients had reliable SLE (mean age 36 [29.5-46] years, duration of disease 9 [3.4-19] years). Of 252 patients, 26 (11%) had PAPS (mean age 36.5 [31-42] years, duration of disease 4.6 [1-10.4] years). Systemic sclerosis was diagnosed in 74/252 (29%) patients, (mean age 51.5 [42-59] years, duration of disease 9 [5-16] years). The quality of the classification function of the criteria was assessed by ROC analysis. SLE was diagnosed in 131 (86%) of 152 patients using the American College of Rheumatology - ACR)-1997 criteria, in 145 (95%) using the The Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria, and in 144 (94.7%) using the European League Against Rheumatism (EULAR)/ACR 2019 criteria. ANF positivity was the least statistically significant of all signs in relation to the diagnosis of SLE. The area under the curve (AUC) for ANF≥1/160 titers was AUC 0.654 for the ACR-97 criteria, AUC 0.616 for the SLICC-12 SLE criteria, and AUC 0.609 for the 2019 EULAR/ACR criteria. ROC analysis of the relationship between the number of criteria/points and a reliable diagnosis of SLE revealed a high diagnostic accuracy - the AUC for all SLE criteria was greater than 0.940. In the ROC analysis of patients with SLE and PAFS, indicating the number of diagnostic criteria, sensitivity was 86% for ACR-1997, 95% for SLICC-2012, 95% for EULAR/ACR 2019, and specificity was 100, 62 and 62%, respectively. The classification criteria SLICC-2012 and EULAR/ACR 2019 are more sensitive for the diagnosis of SLE in the Russian population, and the criteria ACR-1997 are more specific. All three variants of the SLE classification criteria have sufficient sensitivity and specificity for their use in real clinical practice.

Background:Undifferentiated connective tissue disease (UCTD) is a condition characterized by serological evidence of autoimmunity and occurrence of clinical symptoms suggestive of systemic autoimmune diseases, yet not fulfilling specific classification/diagnostic criteria....

BackgroundThe syndrome of incomplete lupus erythematosus (ILE) likely includes individuals at risk for development of systemic lupus erythematosus (SLE). Studies of interventions to lower risk or prevent further disease in...

<h3>Background</h3> Hydroxychloroquine (HCQ) is a mainstay of the initial and long-term treatment of systemic lupus erythematosus (SLE). HCQ blood levels can reflect adherence to the medication and have been correlated...

ObjectiveThe 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria score (≥20 points) has been associated with poor outcomes. We aimed...

To explore the prevalence and clinical significance of low complement levels in patients with catastrophic antiphospholipid syndrome (CAPS). We reviewed data from the "CAPS Registry" on C3 and/or C4 complement plasma protein levels during acute CAPS episodes. Patients were classified into those with low and normal complement levels. Data on clinical presentation, with special focus on thrombotic microangiopathy (TMA) features, diagnosis of systemic lupus erythematosus (SLE), and antiphospholipid antibody (aPL) profile were reviewed. The chi-square exact test was performed to evaluate differences between categorical data. The "CAPS Registry" includes 566 patients with a total of 578 episodes of CAPS. Data on complement plasma protein levels was available in 73 episodes from the same number of patients. Low levels of C3 and/or C4 complement plasma proteins were detected in 42 (58%) CAPS episodes. Low complement levels were more common in SLE patients (55% SLE vs. 19% No SLE; p<0.001). The frequencies of clinical TMA (72% vs. 80%; p=0.4) or TMA syndrome (86% vs. 84%, p=0.9), frequency of triple aPL triple positivity (67% vs 33%; p=0.3), or the mortality (35% vs. 31%; p=0.7) were similar between low and normal complement groups. In our study, low levels of C3 and C4 plasma proteins are detected in 58% episodes of CAPS, which were not associated with clinical presentation including TMA features, aPL triple positivity, or mortality.

Aim:Thyroid dysfunction (TD) and autoimmune thyroid disease (AITD) are frequently reported in patients with systemic lupus erythematosus (SLE). The relationship between SLE disease activity and thyroid disease is controversial. In this study, we aimed to investigate the frequency of TD and AITD in patients with SLE and their relationship with clinical findings and disease activity. Material and Methods:Two hundred SLE patients between the ages of 18 and 75 years, who were followed in the rheumatology outpatient clinic and met the revised 1997 American College of Rheumatology (ACR) SLE classification criteria, were included in the study. Demographic, clinical, and laboratory data of the patients were obtained from patient files and hospital databases. The SLE Disease Activity Index (SLEDAI)- 2 K was used to evaluate SLE disease activity, and the Systemic Lupus International Collaborating Clinics (SLICC)/ACR Damage Index was used to assess damage. Results:AITD was detected in 18.5% of patients with SLE, and 26.5% had TD. Neurological involvement (p=0.017), lymphopenia (p=0.016), hemolytic anemia (p=0.006) and direct coombs positivity (p=0.034) were found to be higher in patients with TD. Female gender (p=0.005), hemolytic anemia (p=0.001), antiphospholipid antibodies (aPL) (p=0.032) and direct coombs positivity (p=0.023) were more common in patients with AITD. When the risk factors were examined, it was determined that neurological involvement [odds ratio (OR)= 6.5], hemolytic anemia (OR= 4.6) and direct coombs positivity (OR= 2.2) increased the risk of TD, whereas aPL positivity and low complement decreased the risk. It was observed that the risk of AITD increased 5.2-fold in the presence of hemolytic anemia. A borderline significant increase in disease activity was observed in patients with TD (p=0.049). When a limit 6 was used for the SLEDAI score, activity was found to be higher in patients with TD (p=0.036). Conclusion:Neurological involvement, hemolytic anemia, and direct Coombs positivity are risk factors for the presence of TD and AITD in SLE.

To evaluate whether a change in the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria threshold score affects accurate classification of SLE cases compared to disease-based control subjects. We evaluated a range of threshold scores to determine the score that maximizes the accurate classification of early SLE. We conducted a cross-sectional study comparing SLE cases and control patients. A EULAR/ACR criteria score was calculated using baseline information. Sensitivity, specificity, positive likelihood ratios (+LRs), and negative likelihood ratios (-LRs) with 95% CIs were used to evaluate operating characteristics. Threshold scores of 6 to 12 were evaluated in subjects with early disease (ie, disease duration of ≤ 5 years). +LRs > 10 and -LRs < 0.1 provide evidence to rule in or rule out SLE. A total of 2764 patients were included: 1980 SLE cases who fulfilled either the ACR or Systemic Lupus International Collaborating Clinics criteria and 784 control subjects. The EULAR/ACR SLE criteria had a sensitivity of 98% (95% CI 97-98), a specificity of 99% (95% CI 98-100), a +LR of 95.5 (95% CI 48.0-190), and a -LR 0.03 (95% CI 0.02-0.03). The criteria operated well in those with early disease, in women, in men, and in White, Black, Chinese, and Filipino people. A score of 10 maximized the accurate classification of patients with early disease (+LR 174.4, 95% CI 43.8-694.6; -LR 0.03, 95% CI 0.02-0.04). An increase in the threshold score from 10 to 11 resulted in significant worsening in the -LR (threshold score 10: -LR 0.03, 95% CI 0.02-0.03 vs threshold score 11: -LR 0.05, 95% CI 0.04-0.06). The EULAR/ACR SLE classification criteria threshold score of 10 performs well, particularly among those with early disease and across sexes and ethnicities.

The new Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria aimed to improve the performance of systemic lupus erythematosus (SLE) classification over the American College of Rheumatology (ACR) 1997 criteria. However, the SLICC 2012 criteria need further external validation. Our objective was to compare the sensitivity for SLE classification between the ACR 1997 and the SLICC 2012 criteria sets in a real-life, multicenter, international SLE population. We conducted a cross-sectional observational study of patients with a clinical diagnosis of SLE followed at the participating rheumatology centers and registered in the Portuguese and Spanish national registries. The sensitivity of the 2 classification sets was compared using McNemar's test. The sensitivity of ACR 1997 and SLICC 2012 was further examined in 5 subgroups, defined according to disease duration. We included 2,055 SLE patients (female 91.4%, white 93.5%, mean ± SD age at disease onset 33.1 ± 14.4 years, mean ± SD age at SLE diagnosis 35.3 ± 14.7 years, and mean ± SD age at the time of the study 47.4 ± 14.6 years) from 17 centers. The sensitivity for SLE classification was higher with the SLICC 2012 than with the ACR 1997 (93.2% versus 85.6%; P < 0.0001). Of 296 patients not fulfilling the ACR 1997, 62.8% could be classified with the SLICC 2012. The subgroup of patients with ≤5 years since disease onset presented the largest difference in sensitivity between the SLICC 2012 and the ACR 1997 (89.3% versus 76.0%; P < 0.0001); this difference diminished with longer disease duration, and it was no longer significant for patients with >20 years of disease duration. The SLICC 2012 criteria were more sensitive than the ACR 1997 criteria in real-life clinical practice in SLE. The SLICC 2012 criteria may allow patients to be classified as having SLE earlier in the disease course.

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