Systemic lupus erythematosus in a tertiary,east Malaysian hospital: admission,readmission and death

Objective: There are limited data on hospitalization of systemic lupus erythematosus (SLE) patients in Asian countries. Our aim of this study is to describe the characteristics and poor prognostic factors in our patients. Method: We performed a retrospective study of SLE hospitalization during a 1‐year period (2006) in our centre. Results: There were 125 episodes of hospitalization of 79 patients with SLE. This is the first report of SLE patients from the native population of east Malaysia. The cause of admission was flare of SLE (80.8%), infection (23.2%), renal biopsy (22.4%) and others (4%). There was only one admission for thromboembolism. Patients with both flare of SLE and infection have the longest median length of stay of 11 days (IQR 5,24) requiring more intensive care therapy (P < 0.01). Readmission occurred in 31.4% and was associated with admission for other reasons during the first admission. Flare of SLE was protective against readmission (P < 0.05, OR = 0.36). There were six deaths (4.8% of admissions). The deaths were due to infection in three patients, active SLE in two and acute myocardial infarction in one. The deaths have a higher cumulative prednisolone dose than the survivals (P < 0.01). In multivariate modelling, the only predictor of death was high Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score (P < 0.05, OR = 9.61 per increase of 1 score). Conclusion: Active disease and infection remains the main cause of admission, readmission and death in SLE patients.     

Hospitalization and outcome of systemic lupus erythematosus patients admitted to the Rheumatology ward of Kasr Al-Ainy University Hospital

Aim of the workTo determine the frequency, causes and disease features affecting outcome of hospitalized systemic lupus erythematosus (SLE) patients, length of hospital stay and the risk factors.Patients and methods132 SLE patients accounting for 167 hospitalizations were recruited from the Rheumatology outpatient clinic, Faculty of Medicine, Cairo University Hospitals during 2019. SLE disease activity index (SLEDAI) and systemic lupus international collaborating clinics damage index (SLICC-DI) were assessed. Data concerning admission was recorded.ResultsThe mean age of the patients was 31.4 ± 10.7 years and disease duration of 91.5 ± 84.3 months. Their mean SLEDAI was 8.7 ± 7.2 and SLICC-DI was 0.87 ± 1.2. The frequency of hospitalization was 167/1456 follow up visits (11.5%): 127 single admissions and 40 recurrent admissions. 137 hospital admissions were females and 30 males (F:M 4.6:1).The most common causes of hospitalization were disease activity in 115/167 hospital admissions (68.9%), infection in 39/167 (23.4%), comorbidities in 33/167 (19.8%). Outcome of hospitalization was improvement in 154/167 (92.2%), morbidity in 7/167 (4.2%), and mortality in 5/167 (3%). Readmission occurred in 40/167 (24%). Higher SLEDAI and gastrointestinal involvement were risk factors for longer hospital stay (p = 0.001 and p = 0.003 respectively). Morbidity was related to higher SLEDAI and SLICC-DI while mortality was related to prolonged azathioprine intake and cardiovascular involvement.ConclusionDisease flare and infection were the most common causes of hospitalization among SLE patients. Higher disease activity and damage as well as cardiovascular involvement were the factors associated with worse outcome. Higher SLEDAI and gastrointestinal involvement were risk factors for longer hospital stay.     

Different genetic effect of PXK on systemic lupus erythematosus in the Korean population

PXK was identified as a novel candidate gene for systemic lupus erythematosus (SLE) from genome-wide association studies (GWAS) in Caucasians. But a recent replication study in Hong Kong Chinese reported that PXK was not associated with SLE. The aim of this study was to determine whether PXK is associated with SLE in Koreans. We genotyped single nucleotide polymorphism (SNP) rs6445975 of PXK using the TaqMan assay in 527 Korean patients with SLE and 517 healthy Korean control subjects. Genotypic associations were assessed using multiple logistic regression models. Additional analyses were also performed by subphenotype stratification. No association was detected between PXK rs6445975 and SLE (odds ratio (OR) = 1.06, P = 0.57). PXK rs6445975 showed positive associations with photosensitivity (P = 0.02) and the production of anti-Sm Ab (P = 0.04) among SLE patients. Thus, the association of PXK rs6445975 with SLE that was previously observed in Caucasians was not replicated in Koreans or in Hong Kong Chinese. It is possible that PXK has different genetic contribution on SLE between Caucasians and Asians and that the gene is associated with disease subphenotypes rather than with overall susceptibility.     

Clinical Outcomes of Patients with Ulcerative Colitis and Co-existing <Emphasis Type="Italic">Clostridium difficile</Emphasis> Infection

Background The incidence of Clostridium difficile infection is increasing in the United States. The aim of our investigation is to compare short-term and long-term outcomes of patients admitted with an ulcerative colitis (UC) flare and co-existent C. difficile infection to those of non-infected patients. Methods A historical cohort study was undertaken examining admissions at Mount Sinai Hospital between June 2004 and June 2005 using ICD-9 criteria for UC. Charts were abstracted for those patients for whom C. difficile testing was performed. Results Of 288 admissions, 99 charts met the inclusion criteria. Fifty-two patients were C. difficile-negative and 47 were positive. Demographic data and laboratory values upon admission did not differ between the two groups. Patients who were C. difficile-positive had significantly more UC-related hospitalizations and emergency room visits in the year following initial admission (58 visits vs. 27, P = 0.001 and eight visits vs. 1 visit (P = 0.012), respectively). One year following the index admission, C. difficile patients had significantly higher rates of colectomy compared to C. difficile-negative patients (44.6% vs. 25%, P = 0.04). Length of hospitalization (11.7 vs. 11 days), use of cyclosporine therapy during index admission (48% vs. 47% of patients), and percentage requiring colectomy at initial admission (23.4% vs. 13.5%) did not reach statistical significance. Conclusions Our data suggest that patients presenting with a UC flare who are infected with C. difficile have worse long-term clinical outcomes than those that are C. difficile-negative. C. difficile testing should be performed for all patients presenting with UC flare. Further studies are warranted to elucidate how infection can alter the natural history of UC.     

Hospitalization of individuals with systemic lupus erythematosus: characteristics and predictors of outcome

We performed a retrospective study of patients with systemic lupus erythematosus (SLE) admitted to hospital during a one-year period to describe characteristics associated with a poor outcome. There were 348 episodes of hospitalization of 223 individuals. The cause of admission was clinical flare of SLE (58%), infection (37%) and thromboembolic disease (8%). Readmission occurred in 35.8% and was associated with: active nephritis (HR 2.53, P < 0.01), flare of lupus (HR 2.0, P < 0.01) and more ACR criteria (HR 1.34 per extra criteria, P < 0.01). Individuals with multiple reasons for admission had a longer duration of stay [one = four days (2, 6), two = five days (3, 7) and three = 9.5 days (6.5, 14.5), P < 0.01]. There were 11 deaths (3.2% of admissions). The deaths were due to infection in nine cases (four with concurrent active SLE). In multivariate modelling, the main predictors of death were: previous multiple admissions (OR 12.4, P < 0.01), the presence of infection (OR 7.3, P < 0.01) and younger age (OR 0.93 per increase of one year, P = 0.03). The presence of active lupus nephritis and multisystem disease makes readmission more likely and individuals with multiple problems at the time of admission have longer hospital stays. Young patients with frequent readmissions and coexistent infections are most likely to die.     

Male gender results in more severe lupus nephritis

Gender may produce different characteristics in the manifestation of systemic lupus erythematosus (SLE). The present study investigated the influence of gender on clinical, laboratory, autoantibodies and histopathological classes of lupus nephritis (LN). As much as 81 patients diagnosed with SLE (ACR criteria) and active nephritis, who underwent renal biopsy between 1999 and 2004, and who had frozen serum samples and clinical data available from the time of biopsy, were selected for this study. The presence of anti-P and antichromatin antibodies was measured using ELISA, and anti-dsDNA was measured using indirect immunofluorescence. All of the renal biopsies were reviewed in a blinded manner by the same expert renal pathologist. The charts were extensively reviewed for demographic and renal features obtained at the time of the biopsy. Of the 81 patients (13.6%), 11 were male SLE patients. Both male and female lupus patients were of similar age and race, and had similar durations of lupus and renal disease. The female patients had more cutaneous (95.7 vs. 45.5%, P = 0.0001) and haematological (52.9 vs. 18.2%, P = 0.04) involvements than the male SLE patients. In addition, the articular data, central nervous system analyses, serositis findings and SLEDAI scores were similar in both experimental groups. Positivity for anti-dsDNA, anti-ribosomal P and antichromatin did not differ between the two groups, and both groups showed similarly low C3 or C4 serum levels. Our analysis indicated that no histopathological class of LN was predominant in both males and females. Interestingly, the serum creatinine levels were higher in the male SLE patients compared to the female SLE group (3.16 ± 2.49 vs. 1.99 ± 1.54 mg/dL, P = 0.03), with an increased frequency of high creatinine (81.8 vs. 47.1%, P = 0.04) as well as renal activity index (7.6 ± 3.5 vs. 4.8 ± 3.5, P = 0.02). In addition, whilst the mean levels of proteinuria, cylindruria and serum albumin were markedly altered, they were comparable between both lupus men and women. Moreover, the frequencies of dialysis, renal transplantation and death were similar between the two groups. These data suggest that male patients had a more severe LN compared to women diagnosed with this renal abnormality.     

The prevalence and significance of monoclonal gammopathy of undetermined significance in acute medical admissions

Monoclonal gammopathy of undetermined significance (MGUS) affects 3·2% of adults aged >50 years. MGUS carries a life-long risk of progression to multiple myeloma and causes complications including infection and renal impairment; common causes of hospital admission. This study aimed to assess MGUS prevalence in emergency medical hospital admissions. Patients were recruited from unselected emergency medical admissions in a hospital in the United Kingdom. Serum protein electrophoresis was performed, with immunofixation of abnormal results. Reason for admission and routine test results were recorded. After education about MGUS and myeloma, patients chose whether they wished to be informed of new diagnoses. A total of 660 patients were tested and 35 had a paraprotein suggestive of MGUS. The overall rate of MGUS was 5·3%. MGUS prevalence in those aged >50 years was 6·94%, higher than the previously published rate of 3·2% (P < 0·0005). There were higher rates in those with chronic kidney disease (13·75% vs. 4·14%, P = 0·002), heart failure (14% vs. 4·59%, P = 0·012), anaemia (8·96% vs. 3·41%, P = 0·003) or leucocytosis (9·33% vs. 3·04%, P = 0·002). In all, 96% of patients wished to be informed of their screening results. The prevalence of MGUS in emergency hospital admissions is higher than expected based on previous population-based rates. This may suggest a selected population for screening.     

Long-term remission after successful pregnancy in autologous peripheral blood stem cell transplanted system lupus erythematosus patients

Pregnancies in systemic lupus erythematosus (SLE) patients are high risk to both mother and fetus because of increased rates of complications. During the past years, we have treated many cases of SLE patients using autologous peripheral blood stem cell transplantation with good outcome after pregnancy. The rate of maternal hypertension and lupus nephritis was greatly reduced in autologous peripheral blood stem cell transplanted group (n = 11) when compared to non-transplant group (n = 39) (P < 0.05). In addition, the outcome of lupus flare activity of the mother after delivery is significantly better in transplanted group than that in non-transplanted group (P < 0.05). Here, we describe two typical cases of long duration (>6 years) of remission after successful pregnancy in refractory SLE patients post-autologous peripheral blood stem cell transplantation. Our report demonstrated that peripheral blood stem cell transplantation is safe and effective, thereby could be recommended as prior strategy in refractory SLE patients, especially for those women of child-bearing age who plan for pregnancy.     

Increased plasma myeloperoxidase levels in systemic lupus erythematosus

The objective of the study was to quantify plasma myeloperoxidase (MPO) levels in systemic lupus erythematosus (SLE) patients and to evaluate a correlation between MPO levels and disease activity. 71 female SLE patients and 70 controls were studied. Patients were divided into two groups: Group I (n = 48) with SLEDAI-2K score 0–5 and Group II (n = 23) with SLEDAI-2K score ≥6. Mann–Whitney test and Spearman rank correlation were used. Two-sided P values <0.05 were considered significant and P values ≥0.05 and <0.08 were considered as a tendency. The median age of patients and controls were comparable and the mean disease duration was 99.2 ± 61.7 months. MPO levels were higher in patients than controls [5.99 (4.38–8.64) vs. 5.00 (3.33–7.08) ng/ml, P = 0.02]. We did not find correlation between MPO levels and SLEDAI-2k (r = 0.07, P = 0.58). MPO levels were not affected by treatment with prednisone, cyclophosphamide or azathioprine, however, a tendency of lower levels was observed among patients under antimalarial drugs. There was no significant difference in MPO plasma levels between Group I and Group II (5.83 vs. 6.02 ng/ml, P = 0.99). MPO levels were higher in patients with arthritis than in those without arthritis (8.15 vs. 5.56 ng/ml, P = 0.010). No difference was observed among patients with and without other organs/systems involvement. SLE patients presented increased MPO plasma levels than healthy controls. Despite the lack of correlation between MPO plasma levels and disease activity, the higher MPO levels in patients with articular involvement suggests MPO may play a different role in the inflammatory process of some SLE manifestations.     

Multi-center evaluation of autoantibodies to the major ribosomal P C22 epitope

Anti-ribosomal P (Rib-P) autoantibodies have been demonstrated to be a specific diagnostic marker for systemic lupus erythematosus (SLE). The aim of this study was to evaluate the prevalence of anti-Rib-P (C22) antibodies in patients with SLE drawn from international, multi-center clinics. Sera collected from patients with SLE (n = 333) and various controls (n = 397) in four centers were tested for anti-C22 autoantibodies by ELISA (Dr. Fooke Laboratorien). SLE activity index 2000 (SLEDAI-2K) was assessed for each patient in two centers. Autoantibody profiles were generated for the SLE samples from Canada using two profile assays. Using the manufacturer`s cut-off value, the prevalence of anti-C22 autoantibodies in patients with SLE between the participating centers varied from 18.2 to 29.0%. In the control sera, the prevalence of anti-C22 autoantibodies was low and the titer in the individual control groups varied significantly. In patients with connective tissue disease other than SLE and in patients with infections disease, the anti-C22 reactivity was significantly higher than in healthy controls (P < 0.0001). Overall sensitivity/specificity was 23.1/99.0%, respectively. Anti-Rib-P reactivity was significantly higher in young (mean age 33.9 vs. 45.3 years) SLE patients (P < 0.0001) and was associated with decreased C3 (P = 0.0335) and C4 levels (P = 0.0129). Moderate association between anti-C22 reactivity and SLEDAI-2K was observed in one cohort (P = 0.02). Anti-C22 autoantibodies are frequently and specifically found in patients with SLE. Although an association between anti-C22 reactivity and SLEDAI score was observed in one center, measurement of anti-C22 autoantibodies is likely not appropriate for measuring global disease activity.     

Lupus and pregnancy studies

Objective. To examine factors prior to pregnancy in patients with systemic lupus erythematosus (SLE) that are prognostic for the occurrence of active disease during and shortly after pregnancy. Methods. Case–control study of pregnant SLE patients and nonpregnant SLE controls, using logistic regression analyses to assess the role of prepregnancy disease activity as a prognostic factor for flare during pregnancy or the postpartum followup period. Results. Lupus flares occurred frequently and in similar percentages of pregnant SLE patients and control SLE patients. Active lupus at study entry, both in control and in pregnant patients, was not predictive of flare. Inactive lupus at onset was not protective against flare in controls but was protective in pregnant lupus patients. Conclusion. Inactive disease at the onset of pregnancy in SLE provides optimum protection against the occurrence of flare during pregnancy.     

Anti‐nucleosome antibodies as a disease activity marker in patients with systemic lupus erythematosus

Aim: To measure the level of anti‐nucleosome antibodies in systemic lupus erythematosus (SLE) patients, to determine the sensitivity and the specificity of these antibodies in the diagnosis of the disease and to evaluate the relationship between the levels of anti‐nucleosome antibodies, anti‐dsDNA (double‐stranded DNA) and SLE disease activity. Methods: A cross‐sectional study was conducted. All patients attended either a medical specialist clinic or were admitted to the medical wards of Hospital Universiti Sains Malaysia with the diagnosis of SLE (n = 90), other connective tissue diseases (n = 45) or were normal controls (n = 90) within the period from July 2004 until September 2005. They were tested for anti‐nucleosome antibodies by enzyme‐linked immunosorbent assay and anti‐DNA antibodies by immunofluorescence. SLE disease activity was evaluated by SLE disease activity index (SLEDAI) score. Results: Out of 90 SLE patients, anti‐nucleosome antibodies were positive in 47 (52.2%) patients, whereas these antibodies were positive in three (6.7%) patients with other connective tissue diseases. Anti‐dsDNA antibodies were positive in 33 (36.7%) SLE patients, whereas these antibodies were positive in four (8.9%) patients with other connective tissue diseases. Anti‐nucleosome antibodies were positive in 40 (97.6%) patients with active SLE, whereas these antibodies were positive in seven (14.3%) patients with inactive SLE. Anti‐nucleosome antibodies had a stronger correlation than anti‐dsDNA antibodies with SLEDAI score. There was a significant association between anti‐nucleosome antibodies and disease activity. Conclusion: Anti‐nucleosome antibodies test is highly sensitive and specific for the diagnosis of SLE, especially when the anti‐dsDNA antibodies are absent. They are additional disease activity markers in the assessment of SLE disease activity.     

Association of increased interferon‐inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus

Objective

To study 5 type I interferon (IFN)–inducible genes (LY6E, OAS1, OASL, MX1, and ISG15) in patients with systemic lupus erythematosus (SLE) and to correlate expression levels with disease activity and/or clinical manifestations.

Methods

Peripheral blood cells were obtained from 48 SLE patients, 48 normal controls, and 22 rheumatic disease controls, and total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real‐time polymerase chain reaction, standardized to a housekeeping gene, and summed to an IFN score. Disease activity was determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA‐SLEDAI) composite.

Results

Each gene was highly expressed in SLE patients compared with normal controls (P ≤ 0.0003) or disease controls (P ≤ 0.0008 except for MX1). IFN scores were positively associated with the SELENA‐SLEDAI instrument score (P = 0.001), the SELENA‐SLEDAI flare score (P = 0.03), and the physician's global assessment score (P = 0.005). Compared with patients without nephritis, lupus nephritis patients had higher IFN scores (overall P < 0.0001), especially during active renal disease. IFN scores were weakly associated with neurologic manifestations. Elevated IFN scores were positively associated with the current presence of anti–double‐stranded DNA (anti‐dsDNA) antibodies (P = 0.007) or hypocomplementemia (P = 0.007). LY6E expression levels distinguished active from inactive lupus nephritis (P = 0.02) and were positively associated with proteinuria (P = 0.009).

Conclusion

The 5 IFN‐inducible genes were highly expressed in SLE patients, and increased levels were correlated with disease activity defined by several methods. IFN scores, or LY6E levels, were elevated in lupus nephritis patients, especially during active renal disease, and in patients with anti‐dsDNA antibody positivity and hypocomplementemia. IFN scores, or LY6E levels, may be useful as a biomarker for lupus nephritis therapy.

     

One Quarter of Medicare Hospitalizations in Patients with Systemic Lupus Erythematosus Readmitted within Thirty Days

ObjectiveThirty-day hospital readmissions in systemic lupus erythematosus (SLE) approach proportions in Medicare-reported conditions including heart failure (HF). We compared adjusted 30-day readmission and mortality among SLE, HF, and general Medicare to assess predictors informing readmission prevention.MethodsThis database study used a 20% sample of all US Medicare 2014 adult hospitalizations to compare risk of 30-day readmission and mortality among admissions with SLE, HF, and neither per discharge diagnoses (if both SLE and HF, classified as SLE). Inclusion required live discharge and ≥12 months of Medicare A/B before admission to assess baseline covariates including patient, geographic, and hospital factors. Analysis used observed and predicted probabilities, and multivariable GEE models clustered by patient to report adjusted risk ratios (ARRs) of 30-day readmission and mortality.ResultsSLE admissions (n=10,868) were younger, predominantly female, more likely to be Black, disabled, and have Medicaid or end-stage renal disease (ESRD). Observed 30-day readmissions of 24% were identical for SLE and HF (p = 0.6), and higher than other Medicare (16%, p < 0.001). Both SLE and HF had elevated readmission risk (ARR 1.08, (95% CI (1.04, 1.13)); 1.11, (1.09, 1.13)). SLE readmissions were higher for Black (30%) versus White (21%) populations, and highest in ages 18–33 (39%) and ESRD (37%). Admissions of Black patients with SLE from least disadvantaged neighborhoods had highest 30-day mortality (9% versus 3% White).ConclusionThirty-day SLE readmissions rivaled HF at 24%. Readmission prevention programs should engage young, ESRD patients with SLE and examine potential causal gaps in SLE care and transitions.     

Vitamin D may not be a good marker of disease activity in Korean patients with systemic lupus erythematosus

Vitamin D is a pleiotrophic hormone with immunoregulatory properties. Low levels of vitamin D have been discovered in various autoimmune diseases. Here, we investigated serum vitamin D levels in Koreans with systemic lupus erythematosus (SLE) and examined whether levels correlate with disease activity of SLE. Blood samples were prospectively collected from patients with SLE (n = 104) and normal controls (NC, n = 49) during the spring from March to May 2008. The level of serum 25-hydroxyvitamin D (25(OH)D3) was measured by radioimmunoassay. The serum 25(OH)D3 levels of patients with SLE (42.49 ± 15.08 ng/ml) were significantly lower than NC (52.72 ± 15.19 ng/ml, P < 0.001). Additionally, 17 patients with SLE (16.3%) had vitamin D insufficiency, while two NC had vitamin D insufficiency (4.1%). The risk of vitamin D insufficiency was 4.6-fold increased in SLE (P = 0.032). The serum 25(OH)D3 levels, adjusted with BMI, were positively correlated only with hemoglobin (β = 0.256, P = 0.018) and serum complement 3 (β = 0.365, P = 0.002). Serum vitamin D levels were lower, and vitamin D insufficiency was more common in Korean patients with SLE, however, our study demonstrated that vitamin D levels might not be a good marker of disease activity.     

Appropriateness,diagnostic value,and outcomes of repeat testing following index echocardiography

Aims

Emergency admission to hospital is associated with an economic burden and mortality. Echocardiography is often the first‐line cardiovascular imaging investigation. Repeat testing is common; however, there are sparse data on the prevalence, appropriateness, or outcome of repeat testing.

Methods

We performed an electronic database search for patients with emergency admissions to our institution in February 2015. An electronic patient record review of inpatient echocardiograms was undertaken. Indications for echocardiography were classified as appropriate, may be appropriate, or rarely appropriate. One‐year follow‐up for repeat testing and mortality was investigated.

Results

A total of 409 of 2306 (17.7%) unplanned/emergency admissions underwent inpatient echocardiography. Abnormalities were identified in 165/409 (40.3%) of these patients; 154 of 409 (37.7%) had a repeat echocardiogram within the next year. Rarely appropriate indications for echocardiography occurred in 51 (33%) of repeat vs 53 (16%) of index echocardiograms, P < .0001. Repeat testing was associated with a change in findings in 17/154 (11%) patients overall. All of whom had an abnormal index echocardiogram and had an appropriate indication. There was no difference in mean survival time between patients who underwent repeat and those who only underwent a single index echocardiogram (310 days vs 327 days), P = .34.

Conclusion

Inpatient echocardiography in emergency hospital admissions identifies clinically important pathology. Repeated testing is common within 1 year of hospital admission. New diagnostic findings occurred in 11% of patients and only in patients with appropriate studies and an abnormal index echocardiogram. Identification of methods to reduce repeat testing and implement appropriateness criteria is warranted.     

Could 2′5′-oligoadenylate synthetase isoforms be biomarkers to differentiate between disease flare and infection in lupus patients? A pilot study

2′5′-Oligoadenylate synthetase (OAS) was shown to be related to systemic lupus erythematosus (SLE) 20 years ago, and was rediscovered to be involved in type I interferon pathway in SLE by several microarray gene expression studies recently. The goal of this study was to investigate OAS isoform expressions in lupus patients, to evaluate whether they could become biomarkers to differentiate between disease flare and infection. Fifty-four SLE patients presented with fever or systemic inflammatory syndrome, or both, were enrolled. Gene expressions of OAS1, OAS2, and OASL were studied by using real time PCR in active SLE (SLEDAI ≥9, n=29) and in those complicated with infections (n=25). The latter group was composed of 19 patients with invasive bacterial infections, and six patients with viral infections. C reactive protein (CRP) and other clinical parameters were also measured. Twenty-nine healthy individuals made up a normal control group. The mRNA expressions of OAS1, OAS2, and OASL were higher in patients with lupus flares than those with infections (p<0.03), or normal controls (p<0.001). SLE complicated with infections have higher OAS1 expression level (P=0.002), lower OASL (P=0.004), and equivalent OAS2 (P=0.135), when compared with those of normal controls. OASL expression level was negatively correlated with infection in lupus by logistic regression analysis (p=0.008). Area under the receiver operating characteristic curve for the prediction of infection was 0.92 (p<0.0001) for OASL, and 0.77 (p=0.007) for CRP. Therefore, our preliminary data suggest that the pattern of OAS isoform expressions, OASL in particular, may provide useful information in differentiating disease flares from certain infections in SLE.     

Interferon‐regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: A validation study

Objective

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by unpredictable flares of disease activity and irreversible damage to multiple organ systems. An earlier study showed that SLE patients carrying an interferon (IFN) gene expression signature in blood have elevated serum levels of IFN‐regulated chemokines. These chemokines were associated with more‐severe and active disease and showed promise as SLE disease activity biomarkers. This study was designed to validate IFN‐regulated chemokines as biomarkers of SLE disease activity in 267 SLE patients followed up longitudinally.

Methods

To validate the potential utility of serum chemokine levels as biomarkers of disease activity, we measured serum levels of CXCL10 (IFNγ‐inducible 10‐kd protein), CCL2 (monocyte chemotactic protein 1), and CCL19 (macrophage inflammatory protein 3β) in an independent cohort of 267 SLE patients followed up longitudinally over 1 year (1,166 total clinic visits).

Results

Serum chemokine levels correlated with lupus activity at the current visit (P = 2 × 10⁻¹⁰), rising at the time of SLE flare (P = 2 × 10⁻³) and decreasing as disease remitted (P = 1 × 10⁻³); they also performed better than the currently available laboratory tests. Chemokine levels measured at a single baseline visit in patients with a Systemic Lupus Erythematosus Disease Activity Index of ≤4 were predictive of lupus flare over the ensuing year (P = 1 × 10⁻⁴).

Conclusion

Monitoring serum chemokine levels in SLE may improve the assessment of current disease activity, the prediction of future disease flares, and the overall clinical decision‐making.

     

Relationship of Circulating Anti-C3b and Anti-C1q IgG to Lupus Nephritis and Its Flare

Background and objectives

Autoantibodies to complement C1q (anti-C1q) are associated with the diagnosis of lupus nephritis. In this study, we compare anti-C1q IgG with another complement autoantibody, anti-C3b IgG, as a biomarker of lupus nephritis and lupus nephritis flare.

Design, setting, participants, & measurements

Our investigation involved the Ohio SLE Study, a prospective observational cohort of patients with recurrently active lupus who were followed bimonthly. Serum anti-C1q and anti-C3b IgG levels were assessed cross-sectionally by ELISA in 40 normal controls and 114 patients in the Ohio SLE Study (41 nonrenal and 73 lupus nephritis) at study entry, and longitudinally in a subset of patients in the Ohio SLE Study with anti-C1q–positive lupus nephritis in samples collected every 2 months for 8 months leading up to lupus nephritis flare (n=16 patients).

Results

In the cross-sectional analysis, compared with anti-C1q IgG, anti-C3b IgG was less sensitive (36% versus 63%) but more specific (98% versus 71%) for lupus nephritis. Only anti-C3b IgG was associated with patients with lupus nephritis who experienced at least one lupus nephritis flare during the Ohio SLE Study period (P<0.01). In the longitudinal analysis, circulating levels of anti-C1q IgG increased at the time of lupus nephritis flare only in patients who were anti-C3b positive (P=0.02), with significant increases occurring from 6 (38% increase) and 4 months (41% increase) before flare. Anti-C3b IgG levels also trended up at lupus nephritis flare, although the change did not reach statistical significance (P=0.07). Neither autoantibody increased 2 months before flare.

Conclusions

Although not as prevalent as anti-C1q IgG, anti-C3b IgG showed nearly complete specificity for lupus nephritis. The presence of anti-C3b IgG identified patients with lupus nephritis who were prone to flare and in whom serial measurements of markers associated with complement, such as anti-C1q IgG, may be useful to monitor lupus nephritis activity.     

Systemic lupus erythematosus in the elderly: antimalarials in disease remission

To analyze the long-term antimalarials (AM) usage on elderly systemic lupus erythematosus (SLE) patients from 2002 to 2008. Fifty-seven consecutive SLE patients,  ≥65 years, were enrolled. The patients were divided into groups A (disease remission) and B (disease activity: with clinical and/or laboratory alterations attributed to SLE activity, and/or using steroid and immunosuppressors). Forty-three patients (75.4%) were in group A. The mean age in groups A and B was, respectively, 69.8 ± 4.5 versus 67.8 ± 4.8 years (P = 0.210), with similar disease onset (46.9 ± 11.2 vs. 42.3 ± 11.6 years; P = 0.220). There was no difference in gender, ethnicity, and clinical previous manifestations. In 21 out of 57 cases (10 from group A and 11, group B, P < 0.001), AM had been suspended after 5.2 ± 1.3 years, because of its side effects (maculopathy). The disease remission was strongly associated to AM usage (OR 12.91; 95% CI 2.87–58.13). In summary, SLE remission was significantly associated with the long-term AM usage.