Serological Markers Of Disease Activity Research Articles

THU420 Analysis Of Factors Affecting Bone Mineral Density In Children And Adolescents With Systemic Lupus Erythematosus

Abstract Disclosure: M. Ahn: None. S. Park: None. B. Suh: None. Background: Children and adolescents with chronic disease are at risk of developing bone fragility. In particular, low bone mineral density(BMD) is increasingly recognized in pediatric patients with glucocorticoid treated rheumatic disease. The purpose of this study was to evaluate the clinical characteristics of children and adolescents with systemic lupus erythematosus(SLE), and to analyze the factors associated with a lower BMD in these patients. Methods: Children and adolescents diagnosed with SLE who had received GC treatment were included. Clinical and laboratory data including anthropometry, GC exposure, other anti-rheumatic drug treatment, biochemical markers related to bone metabolism, serologic markers of disease activity in SLE, lateral thoracolumbar(D-L) spine radiography, and BMD were collected. Lumbar spine bone mineral density (LSBMD) was measured by Dual-energy x-ray absorptiometry(DXA). The correlation between BMD and anthropometry, steroid and anti-rheumatic treatment, biochemical variables was investigated. Results: A total of 30 patients with median age of 17.5 years (range 12 -25years) were included. Of the 29 patients who had DXA done, 7 patients had LSBMD z score lower than −2.0, and diagnosed as osteoporosis. SLE patients with osteoporosis were compared with those with a z score higher than −2.0. These patients had longer GC exposure, higher cumulative GC dose, longer hydroxychloroquine exposure. The main factor correlated with a low BMD was duration of GC exposure. BMD was positively correlated with height at diagnosis. Bone metabolic markers and serologic markers of disease activity in SLE had no significant correlation with BMD. Conclusion: Children and adolescent SLE patients with OP had longer GC exposure, higher cumulative GC dose compared with those with LSBMD z score higher than −2.0. The main factor correlated with a low BMD was duration of GC exposure. Therefore, efforts should be made to reduce the duration of GC exposure and reduce medication to the lower possible maintenance dose. Since longer treatment duration affects BMD, close monitoring during the treatment period is recommended to prevent further loss of bone mass in pediatric SLE patients. Presentation: Thursday, June 15, 2023

MO239: Clinical Evaluation of Immunological and Clinical Recurrence of Immune-Mediated Nephropathies after SARS-COV-2 Vaccine

Abstract BACKGROUND AND AIMS The mass vaccination for COVID-19 has raised new concerns for patients with immune-mediated nephropathies: there is a small but growing literature of case-reports linking SARS-CoV-2 vaccines with heightened off-target immune responses leading to de novo or relapsing glomerular diseases [1, 2]. Aim of this study was to evaluate how many and how severe were the relapses of immune-mediated nephropathies after the SARS-CoV-2 vaccine in a single center. METHOD This is a retrospective study held in Italy from the start of the vaccination campaign (late December 2020) to December 31st 2021. We included all patients with an immune-mediated nephropathy (either on or off immunosuppressive therapy—IS), excluding patients with an end-stage renal disease or kidney transplant. In Italy we used mRNA (Comirnaty by Pfizer-BioNTech or Spikevax by Moderna) or adenoviral vector vaccines (Vaxzevria by AstraZeneca or Janssen), without any preference for patients with kidney disease, but those on active IS were given preferentially an mRNA vaccine. There was no active surveillance of lab tests after vaccination and post-vaccine tests were either concomitant to programmed visits or suggested on a patient by patient basis. Recurrence was defined as relapse of nephrotic or nephritic syndrome, doubling of urinary proteins with a max value > 1 g/24h, acute kidney injury with an active urinary sediment, or positivization or 5-fold increase of serological markers of disease activity (i.e.: ANCA in AAV). RESULTS A total of 38 patients (M: F 28:10, age at vaccine 45.9 ± 19.1 years) completed the vaccination protocol: among them, the most common nephropathy was membranous nephropathy (n = 12, 31.6%), followed by IgA nephropathy (n = 7, 18.4%), minimal change disease (n = 6, 15.8%) and ANCA-associated vasculitis (n = 6, 15.8%); 26 patients (68.4%) had at least one other comorbidity. We observed six relapses (4 MN, 1 IgA, 1 AAV), of which only one (MN) developed a mild oedema. The mean time from the first vaccine dose to the relapse was 101 ± 71 days (5–199 days) and only two episodes occurred within 4 weeks from a vaccine dose. We could not find an association between recurrences and maintenance IS at the time of vaccine or any other variable. The overall post-vaccine incidence rate of relapses was 35.8/100 patient-years, as compared with 14.0/100 patient-years historically observed in the same cohort [IRR 2.55, 95% confidence interval (CI) 0.89–5.97]. CONCLUSION Relapses of immune-mediated nephropathies are not common after SARS-CoV-2 vaccine and we did not observe any clinically relevant relapse. However the overall rate of relapse seems to be a little higher than prior vaccination [3], but only 2/6 patients recurred soon after a vaccine dose. As these relapses seem to be self-limiting, a post-vaccine monitoring could be useful in patients at high risk of severe disease.

Whole-Body MRI with an Ultrahigh b-Value of 2000 s/mm2 Improves the Specificity of Diffusion-Weighted Imaging in Patients with Plasma Cell Dyscrasias

Our study compared sensitivity, specificity, and accuracy of whole-body diffusion-weighted imaging (WB-DWI) using a b-value of 2000 s/mm2 with that of the commonly used b-value of 800 s/mm2 for depiction of active tumor sites in patients with plasma cell diseases. We introduced an ultrahigh b-value to reduce interfering signals from benign and post-therapeutic inactive lesions by suppressing T2-shine-through effects. The prospective single-center study included patients when they went through a whole-body MRI (WB-MRI) staging or response evaluation procedure. The apparent diffusion coefficient (ADC) and morphologic appearance served as reference for classifying focal lesions on WB-DWI as vital or post-therapeutic. Additionally, we compared our classification with patients' serological markers of disease activity. One hundred participants (65 ± 10 years, 58 men) underwent WB-DWI between June and October 2019. The detection rate of vital focal lesions was similar for both b-values with a sensitivity of 0.99 using b = 800 s/mm2 and 0.98 using b = 2000 s/mm2. By contrast, specificity and accuracy were 0.09 and 0.71 when using a b-value of 800 s/mm2, and 0.96 and 0.98 when using a b-value of 2000 s/mm2, respectively. The difference in specificity and accuracy was statistically significant (p < 0.001). Using a b-value of 2000 s/mm2 significantly improved the specificity of lesion detection with WB-DWI as compared to the commonly used b-value of 800 s/mm2. The high b-value significantly reduced signal intensities of post-therapeutic or benign lesions and provided a significantly more accurate representation of active tumor load.

Systemic lupus Erythematosus activity and Hydroxychloroquine use before and after end-stage renal disease

BackgroundSLE manifestations after ESRD may be underdiagnosed and undertreated, contributing to increased morbidity and mortality. Whether specific symptoms persist after ESRD or a shift towards new manifestations occurs has not been extensively studied, especially in the non-Caucasian patients in the United States. In addition, hydroxychloroquine (HCQ) prescribing patterns post-ESRD have not been described. The objective of this study was to assess lupus activity and HCQ prescribing before and after ESRD development. Knowledge gained from this study may aid in the identification of SLE manifestations and improve medication management post-ESRD.MethodsWe performed a retrospective cohort study of SLE patients with incident ESRD between 2010 and 2017. SLE-related symptoms, serologic markers of disease activity, and medication use were collected from medical records before and after ESRD development.ResultsFifty-nine patients were included in the study. Twenty-five (43%) patients had at least one clinical (non-renal) SLE manifestation documented within 12 months before ESRD. Of them, 11/25 (44%) continued to experience lupus symptoms post-ESRD; 9 patients without clinical or serological activity pre-ESRD developed new symptoms of active SLE. At the last documented visit post-ESRD, 42/59 (71%) patients had one or more clinical or serological markers of lupus activity; only 17/59 (29%) patients achieved clinical and serological remission.Thirty-three of 59 (56%) patients had an active HCQ prescription at the time of ESRD. Twenty-six of the 42 (62%) patients with active SLE manifestations post-ESRD were on HCQ. Patients who continued HCQ post-ESRD were more likely to be followed by a rheumatologist (26 [87%] vs 17 [61%], p = 0.024), had a higher frequency of documented arthritis (10 [32%] vs 1 [4%], p = 0.005), CNS manifestations (6 [20%] vs 1 [4%], p = 0.055), and concurrent immunosuppressive medication use (22 [71%] vs 12 [43%], p = 0.029).ConclusionsLupus activity may persist after the development of ESRD. New onset arthritis, lupus-related rash, CNS manifestations, low complement and elevated anti-dsDNA may develop. HCQ may be underutilized in patients with evidence of active disease pre- and post ESRD. Careful clinical and serological monitoring for signs of active disease and frequent rheumatology follow up is advised in SLE patients both, pre and post-ESRD.

PET in the diagnostic management of infectious/inflammatory pulmonary pathologies: a revisit in the era of COVID-19.

PET in the diagnostic management of infectious/inflammatory pulmonary pathologies: a revisit in the era of COVID-19.

Adipokines and periodontal markers as risk indicators of early rheumatoid arthritis: a cross-sectional study.

To establish the association between adipokine levels and markers of periodontal involvement as risk indicators of early stages of RA (eRA) and the interaction between the presence of markers of periodontal disease with adipokine in eRA individuals. Fifty-one patients with a diagnosis of eRA and 51 healthy controls matched for age and sex were studied. Clinical joint condition, clinical and serological markers of disease activity, serum adipokine levels (leptin, adiponectin, resistin, adipsin, vaspin, and IL-6), periodontal diagnosis, presence of Porphyromonas gingivalis, and related IgG1 and IgG2 antibodies were evaluated. Comparisons were made between eRA and healthy controls for periodontal indicators and adipokines. A subgroup analysis was realized with a non-conditional logistic regression to establish the association between the levels of leptin in individuals with eRA and controls according to the periodontal condition, presence of P. gingivalis, or high titers of IgG antibodies against P. gingivalis. The condition of overweight or obesity is associated with the diagnosis of eRA (p = 0.05), and these individuals also have higher levels of leptin (p = 0.001) and vaspin (p = 0.007). Higher frequency of P. gingivalis (p = 0.001) was found in the eRa group. Individuals with eRA with higher IgG2 titers against P. gingivalis had higher levels of leptin (OR: 1.66 (CI 95% 1.01-2.73)); however, individuals with periodontitis or P. gingivalis with eRA were associated with highest levels of leptin (OR: 1.86, CI 95% 1.19-24.3; and OR: 2.04, CI 95% 1.37-3 respectively). eRA individuals have high levels of leptin and vaspin. However, the presence of periodontitis and related-periodontal disease markers showed an effect only in leptin levels in eRA individuals. Emphasizing in personalized medicine, monitoring serum leptin levels and periodontitis markers can improve the early diagnosis of RA.

The utility of serum C-C chemokine ligand 1 in sarcoidosis: A comparison to IgG4-related disease

We previously reported higher levels of C-C chemokine ligand (CCL) 1 in the bronchoalveolar lavage (BAL) fluid (BALF) of patients with sarcoidosis than in BALF of patients with immunoglobulin G4 (IgG4)-related disease (IgG4-RD), indicating that CCL1 might act as a marker of disease activity in sarcoidosis. Notably, less invasive sampling sources are desirable, as BAL cannot always be performed due to its inherent risk. In this study, we sought to decipher the correlation between serum levels of CCL1 and clinical characteristics of sarcoidosis. Serum samples were obtained from 44 patients with clinically confirmed sarcoidosis, 14 patients with IgG4-RD, and 14 healthy controls. The clinical and radiological findings were retrospectively evaluated. Serum levels of CCL1 were measured using a sandwich enzyme-linked immunosorbent assay. Serum levels of other 17 cytokines and chemokines were measured using a MILLIPLEX® MAP KIT and Luminex® magnetic beads. Serum levels of CCL1 were significantly higher in patients with sarcoidosis than in patients with IgG4-RD and healthy controls. Serum CCL1 was positively correlated with the degree of hilar lymph node swelling on chest computed tomography and serum levels of soluble interleukin 2 receptor. Positive correlations were also observed between serum CCL1 and total cell counts, lymphocyte counts in BALF, and serum T helper 1 mediators such as IP-10 and TNF-α in patients with sarcoidosis. Serum CCL1 levels were significantly elevated in sarcoidosis and correlated with clinical parameters of the disease. In addition, serum and BALF levels of CCL1 were positively correlated in a statistically significant manner. Although further research in this field is necessary, CCL1 might have the potential to be a reliable serological marker of disease activity in sarcoidosis.

Validation of the Diagnostic and Prognostic Values of ADAMTS5 and FSTL1 in Osteoarthritis Rat Model.

Osteoarthritis (OA) is a global public health problem and a leading cause of morbidity and disability. Due to lack of sensitive and specific tools for early OA diagnosis and predicting prognosis, the availability of new reliable and sensitive biomarkers is a widely appreciated need to identify patients at risk for incident disease or disease progression. Accordingly, our study was conducted to validate the usefulness of disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and follistatin-like protein 1 (FSTL1) to achieve this goal. Fifty-four male Wistar rats were randomized into 3 groups; 24 rats were subjected to medial meniscal tear (MMT) surgery on the right knee joint (OA group), 24 rats were subjected to sham surgery (sham group), and 6 healthy rats (negative control group). Six animals from each group were sacrificed every 2 weeks. At each time point, the right knee joint of each animal was visualized radiologically, a blood sample was collected, and cartilage tissues were isolated for histopathological and western blot analysis. We found that the expression levels of ADAMTS5 and FSTL1 significantly increased with OA progression, especially at weeks 4, 6, and 8 after surgery. Notably, the serum levels of ADAMTS5 and FSTL1 showed significant positive correlations with each other and with the studied inflammatory markers. Our findings suggest that ADAMTS5 and FSTL1 can serve as important and informative serological markers of disease activity in OA. However, further research is needed to validate their use for improving the diagnosis and prognosis of OA in humans.

Ofatumumab for B cell depletion in patients with systemic lupus erythematosus who are allergic to rituximab.

B cell depletion, most commonly with rituximab, is an evolving therapeutic approach in SLE. Infusion reactions after rituximab are common, and may prevent re-treatment in patients who previously demonstrated beneficial response. We have used ofatumumab, a fully humanized anti-CD20 mAb, as an alternative B cell-depleting agent in patients with SLE who are rituximab-intolerant due to severe infusion reactions. A single-centre retrospective case series of 16 patients were treated with ofatumumab for SLE between 2012 and 2015. Ofatumumab infusion was well tolerated in 14/16 patients, in whom the median age was 34 (range 19-55) and the median duration of SLE 9.2 years (0.6-28.5). The cohort was heavily pre-treated, with 50% having prior CYC exposure, and a median cumulative dose of prior rituximab 4 g (1-6). Twelve patients were treated for LN, one for extra-renal flare and one for remission maintenance. B cell-depletion was achieved in 12/14 patients, with comparable reconstitution kinetics to a previous cohort treated with rituximab at our centre, and was associated with improvements in serological markers of disease activity, including ANA, anti-dsDNA antibody and complement levels. Half of the patients with LN achieved renal remission by 6 months. Progressive disease that was unresponsive to augmented immunosuppression with CYC was seen in five patients. During long-term follow-up (median 28 months), five grade III infections were reported, and there were no malignancies or deaths. In this pre-treated cohort with long-standing SLE, ofatumumab was a well-tolerated, safe and effective alternative to rituximab for B cell-depletion therapy.

Serum level of anti-α-enolase antibody in untreated systemic lupus erythematosus patients correlates with 24-hour urine protein and D-dimer.

Objective The objective of this report is to evaluate the prevalence and clinico-serological correlations of anti-α-enolase antibody (Ab) in patients with systemic lupus erythematosus (SLE). Methods Thirty-two untreated patients with SLE and 20 age- and sex-matched healthy controls were evaluated by rheumatologic examinations. The serum levels of anti-α-enolase Ab were measured by an enzyme-linked immunosorbent assay (ELISA). Clinical, biochemical and serological markers of disease activity were measured by standard laboratory procedure. Results The serum levels of anti-α-enolase Ab in SLE patients were higher significantly than those in healthy controls. Moreover, patients with lupus nephritis displayed significantly higher levels of serum anti-α-enolase Ab than those without renal involvement. The serum anti-α-enolase Ab levels were positively correlated with serum whole IgG and 24-hour urine protein and negatively correlated with serum D-dimer level. Conclusion These data suggest that anti-α-enolase Ab associates with active renal disease in SLE and might reflect a state of active autoimmunity and fibrinolysis inhibition.

Procalcitonin in Crohn's disease with fever episodes, a variable to differentiate intra-abdominal abscess from disease flares

BackgroundCrohn's Disease (CD) is a chronic inflammatory disease accompanied by many complications, such as intra-abdominal abscess (IAA). A frequent problem in CD is the discrimination of fever caused by exacerbated bowel inflammation or IAA. MethodsA total of 80 CD patients complaining with fever episodes were included prospectively. PCT, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WBC) were evaluated on admission. IAA was identified based on image studies and response to antibiotic therapy by physicians blind to the serum PCT level. At last, correlation between serum PCT level and patients' disease activity was also investigated. ResultsSixteen patients were identified with IAA, which showed significantly higher serum PCT level when compared with those patients who have no IAA (0.505 ng/ml vs 0.112 ng/ml, p < 0.01). PCT is a better biomarker of IAA in CD patients compared with CRP, ESR and WBC (AUC = 0.954, 0.757, 0.771 and 0.554, respectively). And the cutoff value for PCT in differentiating patients with and without IAA was 0.35 ng/ml. Correlation between serum PCT level and CDAI score (r = 0.575) was weaker than that of CRP and ESR (r = 0.628 and 0.634 respectively), but stronger than that of WBC (r = 0.162). ConclusionPCT can be an additional marker for detecting IAA in CD patients with fever episodes, and may serve as a new serological marker of disease activity.

Serological markers associated with disease activity in patients with rheumatoid arthritis treated with rituximab.

ObjectiveTo evaluate prospectively serological markers at baseline and during treatment in patients with rheumatoid arthritis (RA) initiating rituximab treatment, following failure of antitumour necrosis factor (TNF)-α therapy.MethodsPatients with RA and healthy control subjects were recruited. Plasma complement (C)3, C4, rheumatoid factor (RF), anticitrullinated protein antibody (ACPA), immunoglobulin (Ig)M, A and G, disease activity scores (DAS) and therapeutic response were recorded at baseline and at 6, 12 and 18 months.ResultsPatients (n = 35) had significantly higher C3 and C4 levels than controls (n = 30). At 12 months after initiation of rituximab, C3 and C4 levels were significantly lower in patients who responded to treatment, compared with nonresponders. There were direct correlations between C3 levels and DAS at 12 months in the study population as a whole, and between IgM levels and DAS in responding patients after 6, 12 and 18 months’ treatment.ConclusionsC3 and IgM levels may represent potentially useful serological markers of disease activity during rituximab treatment in patients with RA.

Elevated levels of serum sCXCL16 in systemic lupus erythematosus; potential involvement in cutaneous and renal manifestations.

The aim of this study was to investigate the levels and clinical significance of serum soluble chemokine (C-X-C motif) ligand 16 (sCXCL16) in patients with systemic lupus erythematosus (SLE), as well as the sCXCL16 molecule's associations with disease activity and organ damage. Thirty-five patients with SLE, 16 patients with rheumatoid arthritis (RA), and 15 healthy controls were included in this study. The demographic and clinical features of the patients were recorded. The serum levels of sCXCL16 were determined. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI), and organ damage was evaluated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI). The serum levels of sCXCL16 in the patients with SLE were higher than those in the patients with RA (P = 0.002) or healthy controls (P < 0.0001). The levels in the patients with active SLE were higher than those in the disease inactive patients (P = 0.008). Positive correlations were identified between serum sCXCL16 concentrations and both SLEDAI (r = 0.564; P < 0.0001) and SDI scores (r = 0.396; P = 0.018). Both SLEDAI (P = 0.021) and serum levels of CXCL16 (P = 0.023) decreased after conventional treatment in 12 initial onset cases of SLE patients. Elevated serum sCXCL16 levels were discovered in the SLE patients with cutaneous (P = 0.006) and renal involvement (P = 0.032). Soluble CXCL16 may become a useful serological marker of disease activity and skin and renal involvement in SLE patients; thus, it may be used for evaluation of therapeutic interventions.

Induction treatment of ANCA-associated vasculitis with a single dose of rituximab

Rituximab is effective in inducing remission in ANCA-associated vasculitis (AAV), with randomized evidence to support its use as four infusions of 375 mg/m(2) (the conventional lymphoma dosing schedule). As B cell depletion (BCD) appears to occur very rapidly after the first dose, we questioned the need for repeat dosing and adopted a standard single-dose protocol of 375 mg/m(2) to treat active AAV. All consecutive cases with newly diagnosed or relapsing AAV for whom conventional immunosuppression was contraindicated or ineffective were enrolled. All were rituximab naive. Circulating CD19(+) B cells and clinical and serological markers of disease activity were recorded at regular intervals. Complete remission (CR) was defined as the absence of clinical features of AAV with a prednisolone dose <10 mg/day. Nineteen patients were included, 17 (89%) with generalized disease and 2 (11%) with severe disease (creatinine level >500 μM). Eight (42%) were on additional immunosuppression at the time of rituximab treatment. Satisfactory BCD (<0.005 cells/μl) was achieved in 89% of patients after a median of 13 days. Three-month BCD probability was 89%. Median time to CR following a single dose of rituximab was 38 days and the 3-month probability of CR was 80%. Median time to B cell repopulation was 9.2 months and to disease relapse/redose was 27 months. Use of this single-dose protocol saved an estimated £4533/patient (US$7103; €5276) compared with a 4 × 375 mg/m(2) dosing schedule. Our single-centre experience suggests that a single dose of rituximab of 375 mg/m(2) is a reasonable and more cost-effective therapy for inducing remission in patients with AAV.

Chylous Ascites and Chylothorax as Presentation of a Systemic Progression of Discoid Lupus

We describe a patient with a history of discoid lupus erythematosus who presented with chylous ascites and chylothorax. Analysis of peritoneal and pleural fluid showed a high level of triglycerides and the presence of antinuclear antibody and anti-dsDNA antibody. Further study revealed other diagnostic criteria for systemic lupus erythematosus and serologic markers of disease activity. The patient was successfully treated with methylprednisolone pulse therapy and high doses of prednisone, followed by immunosuppressants.

Kidney biopsy is a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy

Antibodies against M-type phospholipase A2 receptor (PLA2R) are serological markers of disease activity in patients with idiopathic membranous nephropathy (iMN). To determine the most sensitive test for the diagnosis of PLA2R-related membranous nephropathy (MN) irrespective of sampling time, we investigated the presence of PLA2R in glomerular immune deposits and assessed circulating anti-PLA2R antibodies in a retrospective cohort of Czech patients with idiopathic, lupus and other few secondary MN. We tested archival paraffin-embedded kidney biopsies of 84 consecutive patients with biopsy-proven MN, for the presence of PLA2R in glomerular immune deposits and we measured circulating anti-PLA2R antibodies using the indirect immunofluorescence test, all reagents being commercially available. In 45 of 65 (69%) patients with iMN, PLA2R was detected in a finely granular pattern in sub-epithelial deposits along glomerular capillary loops. Circulating anti-PLA2R antibodies were detected in 20 of 31 (65%) sera from patients sampled during active disease. Six patients with active disease were negative for circulating anti-PLA2R antibodies despite PLA2R antigen positivity in the kidney biopsies. Only 8 of 37 (22%) sera sampled at the time of remission were PLA2R positive while PLA2R antigen was found in 22 of the 37 (59%) corresponding biopsies. PLA2R was found in immune deposits in 3 patients with secondary MN (2 with hepatitis B, and 1 with sarcoidosis) but in none of the 16 patients with lupus. In case of delayed serum sampling, assessment of PLA2R antigen in biopsy specimens is more sensitive than the serological test for the diagnosis of PLA2R-related MN which can be established retrospectively.

Rituximab Therapy in Refractory Neuropsychiatric Lupus: Current Clinical Evidence

To review and summarize published information on the effectiveness and safety of rituximab (RTX) in adult patients with refractory neuropsychiatric systemic lupus erythematosus (NPSLE). We describe a patient with persistently active NPSLE, despite conventional therapy, who responded dramatically to RTX. Current evidence on the therapeutic use of RTX in this complex situation is also analyzed through a systematic review of the English-language literature, based on a PubMed search. Available data on the use of RTX in refractory NPSLE come from a large number of case reports and some open-label studies. Including our case, 35 patients have been well documented. A complete or partial therapeutic response was achieved in 85% of patients after 1 cycle of treatment. A positive correlation between serological markers of disease activity and clinical outcome has also been demonstrated in some of these patients. Clinical improvement was accompanied by a significant reduction in the daily dose of oral corticosteroids. Relapse after RTX treatment was noted in 45% of cases (median 9.5 months; range, 4-33 months). Infections were observed in 29% of patients. Evidence for the effectiveness of RTX as induction therapy in NPSLE is based solely on several case reports and noncontrolled trials. Although it is not yet possible to make definite recommendations, the global analysis of these cases supports the off-label use of RTX in cases of severe refractory NPSLE.

Distinct psychological distress trajectories in rheumatoid arthritis: Findings from an inception cohort

ObjectiveAs with other chronic physical illness, rates of depressive disorder are high in rheumatoid arthritis (RA). The aim of the current study was to identify distinct trajectories of psychological distress over 10years in a cohort of RA patients recruited very early in the course of the disease. MethodsPsychological distress as measured by the Hospital Anxiety and Depression Scale total score was assessed annually in a subgroup of 784 patients enrolled in a multi-centre RA inception cohort (Early RA Study). A latent growth mixture modelling (GMM) approach was used to identify distinct psychological distress patterns. ResultsFour distinct psychological distress trajectories were observed: low-stable (68%), high-stable (12%), high-decreasing (9%) and low-increasing (11%). Symptoms of pain, stiffness and functional impairment were significantly associated with levels of psychological distress at the time of diagnosis and after 3years; serological markers of disease activity (ESR and CRP) were not. ConclusionsAlthough the majority of individuals developing RA experience little or no impact of the effects of the disease on their psychological well-being, a significant proportion experience high levels of distress at some point which may be related to their subjective appraisal of their condition. Assessment and treatment of psychological distress should occur synchronously with somatic symptoms.

Factores asociados con actividad del lupus eritematoso sistémico en insuficiencia renal crónica terminal

la actividad del lupus eritematoso sistémico (LES) tiende a disminuir en pacientes que desarrollan enfermedad renal crónica terminal (ERCT). Sin embargo, la actividad extrarrenal no es infrecuente, especialmente en los primeros años de la diálisis. Nosotros estudiamos el curso clínico y evaluamos la actividad del LES en pacientes con ERCT en diálisis por más de seis meses. El objetivo de este estudio fue identificar los factores asociados con actividad lúpica durante la diálisis. se evaluaron retrospectivamente 15 pacientes con diagnóstico de LES quienes recibieron diálisis de mantenimiento en nuestro centro desde 2000 a 2009. Revisamos sus características clínicas, marcadores serológicos de actividad lúpica y actividad de la enfermedad según el SLEDAI. Se compararon los pacientes que presentaron exacerbaciones con quienes no presentaron exacerbaciones del lupus durante la diálisis de mantenimiento. el tiempo transcurrido entre el diagnóstico del LES y el inicio de la diálisis fue de 40.3 meses (6.3-84.3) y la duración de la diálisis fue de 21.8 meses (12.0-40.0). Ocho pacientes presentaron nueve episodios de exacerbación del LES durante la diálisis. Cuatro (44.4%) se presentaron durante el primer año de la diálisis. En comparación con las otras siete pacientes que no tuvieron exacerbaciones durante la diálisis, las pacientes con exacerbaciones fueron más jóvenes al inicio de la diálisis [22.4 años (17.9 – 24.9) vs 30.6 años (26.2 – 40.1); p = 0.021] y tuvieron niveles séricos de C3 significativamente menores al inicio de la diálisis [63.5 mg/dl (57.5 – 67.5) vs 90 mg/dl (87.5 – 105), p = 0.006]. la actividad lúpica no siempre se “apaga” en pacientes que progresan a ERCT. Pacientes con una edad más joven y niveles más bajos de C3 al inicio de la diálisis pueden tener un mayor riesgo de presentar exacerbaciones del lupus durante la diálisis. Se recomienda un seguimiento cuidadoso de los pacientes lúpicos que reciben terapia dialítica mediante un monitoreo clínico y serológico, particularmente para aquellos considerados como potenciales receptores de trasplante renal. the activity of systemic lupus erythematosus (SLE) tends to decline in patients who develop end-stage renal disease (ESRD). However, extrarenal activity is not uncommon, particularly during the first few years of dialysis. We studied the clinical course and assessed the SLE activity in patients with ESRD on dialysis for more than six months. The objective of this study was to identify factors associated with postdialysis activity. fifteen patients with SLE who were given maintenance dialysis in our center from 2000 to 2007 were examined retrospectively. Their clinical characteristics, serological markers of disease activity and disease activity as per systemic lupus erythematosus disease activity (SLEDAI) were reviewed. Patients with and without postdialysis lupus flares were compared. the time between SLE diagnosis and the onset of dialysis was 40.3 months (6.3-84.3) and the duration of dialysis was 21.8 months (12.0-40.0). Eight patients experienced 9 lupus postdialysis flares. Four flares (44.4%) occurred within the first year of dialysis. Compared with the other 7 patients who had no flares during dialysis, patients with flares were younger at the onset of dialysis [22.4 years (17.9 – 24.9) vs 30.6 years (26.2 – 40.1); p = 0.021] and had serum levels of C3 significantly lower at the onset of dialysis [63.5 mg/dl (57.5 – 67.5) vs 90 mg/dl (87.5 – 105), p = 0.006]. lupus activity does not always “burn out” in patients who progress to ESRD. Younger patients at the onset of dialysis and lower levels of C3 at the start of dialysis may have higher risk of postdialysis lupus flare. SLE patients on dialysis should be carefully followed up by clinical and serological monitoring, particularly in potential renal transplant recipients.

Detecting clinical activity in systemic lupus erythematosus with an archaeal poly(ADP-ribose) polymerase-like thermozyme: a pivotal study

The clinical usefulness of an immunotest was evaluated by using purified poly(adenosine diphosphate (ADP)-ribose) polymerase from Sulfolobus solfataricus (PARPSso) as an antigen to detect the presence of abnormal anti-PARP antibodies in the sera of patients with systemic lupus erythematosus (SLE) at different clinical stages. Sera from 44 patients with SLE, subgrouped on the basis of disease activity (16 with inactive disease, 28 with active disease) were analysed with a new immunotest to detect anti-PARP antibodies, and with an immunofluorescent (IIF) assay for antinuclear antibodies (ANA) detection. ANA detection by IIF revealed that sera of healthy subjects were negative, whereas sera from patients with SLE were positive in all cases (13 positive at 1:80, 15 at 1:160, 15 at 1:320, 1 at 1:640, v/v). Anti-PARP activity was higher in ANA-positive patients than in controls (p = 0.005). Within the group of SLE sera, disease and anti-PARP activity was increased more significantly in patients with active than in those with inactive disease (p < 0.001 and p = 0.001, respectively). Correlation between anti-PARP and disease activity in SLE patients was statistically significant (p < 0.001). PARPSso seems to be suitable for detecting anti-PARP antibodies and could play a role as a serological marker of disease activity in patients with SLE.