Tumid lupus erythematosus is a rare variant of chronic cutaneous lupus erythematosus that is characterized clinically by smooth, nonscarring, pink to violaceous papules or plaques without evidence of surface change. Histopathologic features include superficial and deep lymphocytic infiltration in a perivascular and periadnexal distribution, with dermal interstitial mucin deposition and focal or absent dermoepidermal junction involvement. These clinical and histopathologic features can be challenging to differentiate from other cutaneous diseases. This is particularly true because patients with tumid lupus erythematosus usually do not have other manifestations of systemic lupus erythematosus or cutaneous lupus erythematosus. We present two cases of tumid lupus erythematosus, one associated with concomitant systemic lupus erythematosus and the other occurring concurrently with discoid lupus erythematosus. Furthermore, we demonstrate the rare occurrence of a patient with tumid LE occurring below the waist at a photoprotected site.
tumid lupus erythematosus; systemic lupus erythematosus; discoid lupus erythematosus; chronic cutaneous lupus erythematosus
Systemic lupus involves different body organs including lungs. However, there is limited information on the systemic lupus without respiratory symptoms. The aim of this study was to investigate the diffusing capacity of the lung for carbon monoxide in women with disseminated lupus erythematosus and to compare it with a control group.
This prospective study was conducted during 2005 in the Rheumatology Clinic of Alzahra Hospital, Isfahan, Iran. The diffusing capacity of the lung for carbon monoxide and pulmonary parameters were measured using the unrelated samples in 76 female patients with systemic lupus.
Mean diffusing capacity of the lung for carbon monoxide in patients with lupus was lower than the control group (P ≤ 0.001). The amount of corrected volumetric capacity of carbon monoxide in lungs of patients was significantly different from the control group (P ≤ 0.001). Residual volume and total capacity of lungs in the female patients with lupus were higher than the control group (P ≤ 0.001).
Decreased diffusing capacity for carbon monoxide in lungs of females with systemic lupus without respiratory symptoms is prevalent. It indicates alveolar capillary membrane involvement in these patients. Increased residual volume and total capacity of lungs in these patients can be caused by bronchiolitis.
Lupus Erythematosus; Transfer Capacity; Carbon Monoxide in Lungs; Total Capacity of Lungs
Interstitial lung diseases (ILDs) represent a heterogeneous group of more than two hundred diseases of either known or unknown etiology with different pathogenesis and prognosis. Lung cancer, which is the major cause of cancer death in the developed countries, is mainly attributed to cigarette smoking and exposure to inhaled carcinogens. Different studies suggest a link between ILDs and lung cancer, through different pathogenetic mechanisms, such as inflammation, coagulation, dysregulated apoptosis, focal hypoxia, activation, and accumulation of myofibroblasts as well as extracellular matrix accumulation. This paper reviews current evidence on the association between lung cancer and interstitial lung diseases such as idiopathic pulmonary fibrosis, sarcoidosis, systemic sclerosis, dermatomyositis/polymyositis, rheumatoid arthritis, systemic lupus erythematosus, and pneumoconiosis.
The aim of this study was to determine the factors associated with metabolic syndrome in patients with systemic lupus erythematosus from Puerto Rico. A total of 204 patients with systemic lupus erythematosus (per the American College of Rheumatology classification criteria) were evaluated. Metabolic syndrome was assessed using the American Heart Association and the National Heart, Lung, and Blood Institute classification. Socioeconomic–demographic parameters, health-related behaviours, clinical manifestations, autoantibodies, pharmacological treatments, disease activity (per the Systemic Lupus Activity Measure—Revised), and damage accrual (per the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were determined at study visit. Factors associated with metabolic syndrome were examined by univariable analyses and multivariable logistic regression models. A total of 196 (96.2%) were women. The mean age at study visit was 43.6 ± 13.0 years, and the mean disease duration was 8.7 ± 7.7 years. Seventy-eight patients (38.2%) had metabolic syndrome. In the multivariable analysis, age (odds ratio [OR] = 1.05; 95% confidence interval [CI] 1.02–1.09), government health insurance (OR = 2.06; 95% CI 1.07–4.22), exercise (OR = 0.33; 95% CI 0.14–0.92), thrombocytopenia (OR = 4.19; 95% CI 1.54–11.37), erythrocyte sedimentation rate (OR = 1.64; 95% CI 1.03–2.63), disease activity (OR = 1.14; 95% CI 1.00–1.30), and prednisone >10 mg/day (OR = 3.69; 95% CI 1.22–11.11) were associated with metabolic syndrome. In conclusion, older age, low socioeconomic status, lack of exercise, thrombocytopenia, increased erythrocyte sedimentation rate, higher disease activity, and prednisone >10 mg/day were independently associated with metabolic syndrome in patients with systemic lupus erythematosus from Puerto Rico.
cardiovascular disease; haematologic changes; systemic lupus erythematosus; Metabolic syndrome; Puerto Rico
Background: Although crystalline silica exposure is associated with silicosis, lung cancer, pulmonary tuberculosis, and chronic obstructive pulmonary disease (COPD), there is less support for an association with autoimmune disease, and renal disease.
Methods: Using data from the US National Occupational Mortality Surveillance (NOMS) system, a matched case-control design was employed to examine each of several diseases (including silicosis, lung cancer, stomach cancer, oesophageal cancer, COPD, pulmonary tuberculosis, sarcoidosis, systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and various types of renal disease). Cases were subjects whose death certificate mentioned the disease of interest. A separate control group for each of the diseases of interest was selected from among subjects whose death certificate did not mention the disease of interest or any of several diseases reported to be associated with crystalline silica exposure. Subjects were assigned into a qualitative crystalline silica exposure category based on the industry/occupation pairing found on their death certificate. We also investigated whether silicotics had a higher risk of disease compared to those without silicosis.
Results: Those postulated to have had detectable crystalline silica exposure had a significantly increased risk for silicosis, COPD, pulmonary tuberculosis, and rheumatoid arthritis. In addition, a significant trend of increasing risk with increasing silica exposure was observed for these same conditions and for lung cancer. Those postulated to have had the greatest crystalline silica exposure had a significantly increased risk for silicosis, lung cancer, COPD, and pulmonary tuberculosis only. Finally, those with silicosis had a significantly increased risk for COPD, pulmonary tuberculosis, and rheumatoid arthritis.
Conclusions: This study corroborates the association between crystalline silica exposure and silicosis, lung cancer, COPD, and pulmonary tuberculosis. In addition, support is provided for an association between crystalline silica exposure and rheumatoid arthritis.
Several series have suggested that pulmonary function abnormalities are common in systemic lupus erythematosus. However, only isolated studies have attempted to relate these abnormalities to immunological aspects of the diseases. In the present study respiratory symptoms, pulmonary function tests, and immunological data were reviewed in 22 patients with systemic lupus erythematosus. Seventeen subjects had either clinical evidence or abnormalities of lung function suggestive of pulmonary involvement. A restrictive ventilatory defect or reduction in pulmonary diffusing capacity for carbon monoxide was demonstrated in 14 of the patients only 4 of whom were dyspnoeic. There was no correlation between pulmonary involvement, co-existent renal lupus, and immunological abnormality.
The goal of the present study was to estimate the risk ratio of herpes zoster among systemic lupus erythematosus patients after disease onset compared with a cohort of patients without systemic lupus erythematosus over a three-year period.
A nationwide population-based cohort study using the National Health Insurance Research Database identified 10,337 new cases of systemic lupus erythematosus as the study cohort. In addition, 62,022 patients without systemic lupus erythematosus, who were matched for age, gender, and date of systemic lupus erythematosus diagnosis, were used as the comparison cohort. These cohorts were followed-up for three years. A Cox proportional hazard regression was performed to estimate the risk ratio of herpes zoster, with adjustments for age, gender, level of insurance, urbanization level, geographic region, comorbid medical conditions, average daily dosage of corticosteroids, and the use of immune-modulation agents.
Compared to patients without systemic lupus erythematosus, the crude risk ratio and adjusted risk ratio of herpes zoster among systemic lupus erythematosus patients were 7.37 (95% confidence interval 6.75-8.04) and 2.45 (95% confidence interval 1.77-3.40), respectively. Stratified by gender, the adjusted risk ratio of herpes zoster was 2.10 (95% confidence interval 1.45-2.99) in women and 7.51 (95% confidence interval 2.89-19.52) in men. Stratified by age, the adjusted risk ratio peaked in systemic lupus erythematosus patients who were aged 18 to 24 years (risk ratio 8.78, 95% confidence interval 3.08-24.97).
Based on nationwide population-based data, there is an increased risk of herpes zoster in systemic lupus erythematosus patients compared with non-systemic lupus erythematosus patients, particularly among males and patients aged 18 to 24 years. Further research on the associated risk factors for herpes zoster in systemic lupus erythematosus patients is needed.
Herpes Zoster; Risk; Systemic Lupus Erythematosus; Population-Based Cohort Study; Database
The diagnostic significance of anti-double-stranded deoxyribonucleic acid (anti-dsDNA) determination was evaluated in a prospective manner from 1974 to 1982 in a group of 441 patients without systemic lupus erythematosus whose sera were found to contain antibodies to dsDNA on routine screening (Farr assay). Within one year 69% (304) of these patients fulfilled the preliminary American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). Eighty-two of the remaining 137 patients were followed up for several years. At the end of the study 52% of these patients had also developed systemic lupus erythematosus. Patients who developed systemic lupus erythematosus were characterised by the occurrence of relatively high avidity anti-dsDNA in the circulation compared with patients who did not develop systemic lupus erythematosus. It can be concluded that about 85% of patients without systemic lupus erythematosus with anti-dsDNA in the circulation will develop SLE within a few years. Taking into account the relative avidity of anti-dsDNA, as determined by calculation of Farr/polyethylene glycol (PEG) ratios, we conclude that patients with relatively high avidity anti-dsDNA are more prone to develop systemic lupus erythematosus than patients with relatively low avidity anti-dsDNA.
Blood rheology is one of the determinants of perfusion and might therefore have an impact on the thromboembolic complications of lupus erythematosus. This study aimed at defining the flow properties of blood in patients with various types of lupus erythematosus. Results for 51 patients were compared with those for 20 controls matched for sex. The patients were divided into subgroups--chronic discoid, subacute cutaneous, and systemic lupus erythematosus--according to their clinical or laboratory characteristics. Blood and plasma viscosity, packed cell volume, red cell aggregation, and red cell deformability were used as parameters of blood rheology. Blood and plasma viscosity and red cell aggregation were significantly different in patients compared with controls, indicating reduced blood fluidity in lupus erythematosus. There were no marked sex differences. The rheological effects were greater in those with systemic lupus erythematosus than in those with chronic discoid or subacute cutaneous lupus erythematosus. The presence of a positive antinuclear antibody titre or methods of treatment (systemic steroids or retinoids) had no apparent effect on the parameters tested. It is suggested that a complex haemorheological deficit exists in lupus patients.
What have we learnt about cancer risk in systemic lupus erythematosus (SLE) over the past decade? One important lesson is that data do confirm a slight increased risk in SLE for all cancers combined, compared to the general population. However, it is clear that this is largely driven by an increased risk for hematological malignancies, particularly non-Hodgkin’s lymphoma (NHL), although Hodgkin’s lymphoma may be increased as well. In addition, there is evidence for a moderately increased risk of lung cancer, and possibly for rarer cancer types, such as hepatobiliary and vulvar/vaginal malignancies.
Unfortunately, the most clinically relevant question, the mechanism underlying the association between cancer and SLE, remains largely unanswered. Key issues remaining under study relate to the links between cancer risk, SLE disease activity, and medication exposures. Much of the recent data suggest that disease-related factors may be at least as important as medication exposures for certain cancers, such as NHL. The independent effects of drug exposures versus disease activity in mediating cancer risk in SLE remain unknown. Work is in progress to further elucidate these important issues.
Meanwhile, there is good evidence that cervical dysplasia is increased in women with SLE. This may be mediated by decreased clearance of the human papilloma virus, which some suggest is an innate characteristic of SLE patients. However, an increased risk of cervical dysplasia is also associated with immunosuppressive medication exposures, particularly cyclophosphamide. For these reasons, it is important that women with SLE follow established guidelines for cervical cancer screening.
Malignancy; cancer; systemic lupus erythematosus; SLE; lymphoma; NHL
Granulomatous lesions are commonly encountered abnormalities in pulmonary pathology, and often pose a diagnostic challenge. We report an unusual case of granulomatous lung disease with uncommon characteristics, which developed following Epstein-Barr-virus-induced mononucleosis and new-onset systemic lupus erythematosus. We aim to highlight a diagnostic approach for the condition and to raise awareness of the possibility of it being related to the immunological reaction caused by Epstein-Barr virus infection.
A 36-year-old Japanese man, who had been diagnosed with Epstein-Barr-virus-induced infectious mononucleosis, new-onset systemic lupus erythematosus, and secondary Sjögren’s syndrome three weeks previously, presented to our facility with fever and diffuse pulmonary infiltrates. A computed tomography scan of the chest revealed multiple small nodules in both lungs. Fiberoptic bronchoscopy with bronchoalveolar lavage revealed lymphocytosis with predominance of T lymphocytes. A histological examination of a lung biopsy taken during video-assisted thoracic surgery showed randomly distributed tiny granulomatous lesions with infiltration of eosinophils. The differential diagnoses included hypersensitivity pneumonitis, sarcoidosis, and pulmonary involvement of Crohn’s disease, systemic lupus erythematosus, and Sjögren’s syndrome, but the clinical and pathological findings were not consistent with any of these. Our patient’s condition did not improve; therefore, prednisolone therapy was started because of the possibility of specific immunological reactions associated with Epstein-Barr virus infection. After steroid treatment, our patient showed radiological and clinical improvement.
To the best of our knowledge, this is the first case of a patient developing randomly distributed multiple granulomatous lung lesions with eosinophilic infiltrates after Epstein-Barr virus infection and systemic lupus erythematosus. On the basis of our data, we hypothesize that Epstein-Barr virus infection altered the immune response of our predisposed patient and contributed to the pathogenesis of the lung lesions. Our patient’s clinical response to steroid treatment was excellent.
Centrilobular micronodules; Epstein-Barr virus; Granulomatous lesions; Lung; Sjögren’s syndrome; Systemic lupus erythematosus
BACKGROUND: In systemic lupus erythematosus, certain laboratory tests and evidence from muscle biopsy specimens of lymphocytic vasculitis reflect disease activity. A study was designed to determine if such indices predict respiratory lesions, and in particular whether the presence of vasculitis in quadriceps muscle reflects respiratory muscle function. METHODS: Twenty seven 27 patients with systemic lupus erythematosus were studied, ten of whom were consecutive untreated patients and 17 having clinically active disease and being treated. They were prospectively evaluated on the basis of erythrocyte sedimentation rate, lymphocyte count, C3 degradation products, quadriceps muscle biopsy, spirometry, lung volumes, carbon monoxide transfer factor, and mouth pressure during a maximal sniff. RESULTS: Lung function test results were abnormal in 12 patients. Vital capacity was reduced in seven, carbon monoxide transfer factor capacity in five, and mouth pressure was low (< 70% predicted) in ten. Lymphocytic vasculitis was seen in the muscle biopsy specimens of ten patients. No correlation was found between laboratory tests and lung function or mouth pressure, or between the presence of lymphocytic vasculitis and mouth pressure. In untreated patients, those with lymphocytic vasculitis had lower spirometric values. CONCLUSIONS: In systemic lupus erythematosus, evidence from muscle biopsy specimens of lymphocytic vasculitis is not predictive of impaired inspiratory muscle function as measured by mouth pressure. In untreated patients there were relationships between some laboratory test results and respiratory function, but this was not the case for the whole group. In systemic lupus erythematosus, laboratory tests and evidence from muscle biopsy specimens of lymphocytic vasculitis are therefore unlikely to be helpful in the assessment of respiratory disease.
To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features.
We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay.
We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33±4.50), 64 first-degree relatives (mean age 39.95±5.66), and 57 healthy (mean age 19.30±4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their first-degree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels.
Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares.
Interferon alpha (IFN-α); SLEDAI; Childhood-onset; Systemic lupus erythematosus
A 38-year-old patient with systemic lupus erythematosus presented with pulmonary infiltrates and hypoxemia for several months following immunodepleting autologous hematopoietic stem cell transplantation. She was treated for influenza, which was isolated repeatedly from ororpharynx and bronchoalveolar lavage fluids, and later empirically for lupus pneumonitis, but expired 6 months after transplant. Autopsy findings failed to show influenza in the lungs or lupus pneumonitis. A novel generic PCR-based assay using degenerate primers identified human coronavirus HKU1 RNA in bronchoalveolar lavage fluid at autopsy. Coronavirus was confirmed by virus-specific PCRs of lung tissue at autopsy. Electron microscopy showed viral particles consistent with coronavirus HKU1 in lung tissue both at autopsy and from a previous biopsy. While human coronavirus HKU1 infection is not usually severe, in highly immunocompromised patients, it can be associated with fatal pneumonia.
Viral infections; generic virus detection; virus discovery; immunocompromised
Systemic lupus erythematosus is a chronic inflammatory autoimmune disease which damages tissue and organs. Circulation, kidney, lungs, liver, central and peripheral nervous systems, joints and skin may be damaged. It also often involves psychotic syndromes which might even be stimulated by glucocorticoid therapy. In the following article we present the case report of psychotic symptoms in a 26-year old patient after management of aortic stenosis in systemic lupus erythematosus receiving glucocorticoid therapy.
systemic lupus erythematosus; aortic stenosis surgery; psychotic symptoms
Antiphospholipid syndrome is a well-defined entity that is characterized by spontaneous abortion, thrombocytopenia, and recurrent arterial and venous thromboses. A partially calcified right atrial thrombus mimicking myxoma with recurrent pulmonary embolism has not been previously reported in a patient who also had systemic lupus erythematosus and secondary antiphospholipid syndrome.
Herein, we describe the case of a 37-year-old woman with systemic lupus erythematosus and secondary antiphospholipid syndrome who was admitted to the hospital with progressive exertional dyspnea. Ventilation-perfusion scanning showed multiple parenchymal defects in the lungs that portended pulmonary embolism. In addition, the scanning revealed normal regional ventilation. Transthoracic and transesophageal echocardiography showed a right atrial mass that was highly suggestive of myxoma, and the patient subsequently underwent surgery. A histologic examination showed an organized, partially calcified thrombus.
Intracardiac thrombus has been rarely reported as a complication of antiphospholipid syndrome. In our patient, the preoperative investigations could not differentiate the partially calcified right atrial thrombus from a myxoma, and the diagnosis was made postoperatively.
Antibodies, anticardiolipin/blood; antiphospholipid syndrome/complications; autoimmune diseases/complications; coronary thrombosis/complications/diagnosis/epidemiology/radiography/surgery; heart atria; heart neoplasms/diagnosis; lupus erythematosus, systemic/complications; myxoma/diagnosis; recurrence; thrombosis/complications/diagnosis/etiology/pathology/prevention & control/surgery
The aim of this study was to investigate the frequency of pulmonary function abnormalities in clinically asymptomatic children with Systemic Lupus Erythematosus and to determine the relationship of these abnormalities to clinical, laboratory, and immunological parameters as well as to disease activity.
Forty-two children with childhood onset Systemic Lupus Erythematosus were included in this study. Demographic, clinical, laboratory and immunological parameters, as well as disease activity were assessed. Pulmonary function tests (PFT) were performed routinely to screen for subclinical lung disease.
Out of the 42 children, 19% (n=8) had clinical evidence of pulmonary involvement. The patients with no clinical evidence of pulmonary involvement (n=34) represent the study cohort. From our cohort of patients with no clinical evidence of pulmonary involvement 79% (n=27) had PFT abnormality; including 62% (n=21) had reduced FVC, 71% (n=24) had reduced FEV1, and 67% (n=12) had reduced DLCO. Similarly, 56% (n=15) had a restrictive PFT pattern, and 2.6% (n=2) had an obstructive PFT pattern, while 33% (n=7) had an isolated impairment of diffusion capacity. Due to small sample size; it was not possible to find a statistically significant difference between the cohort of asymptomatic SLE patients with abnormal PFT findings (n=27) and those with normal PFT findings (n=7) in terms of clinical, laboratory, immunological or disease activity index score.
Subclinical lung disease, as demonstrated by abnormal PFT in patients with normal radiographs, may be common but should be interpreted with caution as an early sign of lung disease. Although PFT studies do not correlate well with pulmonary symptoms in patients with childhood onset SLE, they nevertheless provide objective quantification of the type and severity of the functional lesions.
Systemic lupus erythematosus; Pulmonary; Prevalence; Oman
The lupus anticoagulant was found in the plasma of 31 of 60 patients with systemic lupus erythematosus and other connective tissue disorders (mixed connective tissue disease, systemic vasculitis, polyarteritis nodosa, primary sicca syndrome, discoid lupus, Behcet's syndrome, and systemic sclerosis). Strong associations were found with biological false positive seroreaction for syphilis and thrombocytopenia. The most striking association, however, was with the high prevalence of thrombosis. This tendency to thrombosis was independent of disease activity of systemic lupus erythematosus. The lupus anticoagulant appears to be a useful marker for a subset of patients with systemic lupus erythematosus at risk for the development of thromboembolic complications.
To describe the clinical utility of the nicotinic ganglionic acetylcholine receptor (α3-AChR) autoantibody as a marker of neurological autoimmunity and cancer.
Mayo Clinic, Rochester, Minnesota.
A total of 15 000 patients seen at Mayo Clinic (2005–2007) and evaluated on a service basis for paraneoplastic neurological autoimmunity for whom clinical information was obtained retrospectively by medical record review as well as 457 neurologically asymptomatic patients or control subjects of whom 173 were healthy, 245 had lung cancer, and 39 had systemic lupus erythematosus or Sjögren syndrome.
Neurological, oncological, and serological associations of α3-AChR autoantibody seropositivity.
Of 15 000 patients tested on a service basis, 1% were seropositive (median, 0.12 nmol/L; range, 0.03–18.8 nmol/L; normal, ≤0.02 nmol/L), 55% were male, and the median age was 65 years. Cancer was found (new or by history) in 24 of 78 patients evaluated for cancer while at Mayo Clinic (30%); 43% had adenocarcinoma (more patients had breast cancer than prostate, lung, and gastrointestinal cancers; each of the latter groups had about the same number of patients). Of 12 patients with high antibody values (≥1.00 nmol/L), 83% had pandysautonomia. Of 85 patients with medium antibody values (0.10–0.99 nmol/L), neurological presentations were more diverse and included peripheral neuropathies (36%), dysautonomia (20%, usually limited), and encephalopathy (13%). Of 58 patients with low antibody values (0.03–0.09 nmol/L), 54% had a nonautoimmune neurological disorder or no neurological disorder. Of 245 control patients with lung cancer, 7.8% were seropositive. Only 1 of 212 control patients without cancer (0.5%) was seropositive (P<.001).
The detection of α3-AChR autoantibody aids the diagnosis of neurological autoimmunity and cancer.
Microchimerism has been studied in the context of a variety of diseases which include autoimmune diseases (such as systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid diseases), cancer (e.g., of the cervix, thyroid gland, lung, breast), tissue repair, transplantation and transfusion. It may become relevant in the context of cell-based non-invasive prenatal diagnosis. But how to safely identify individual microchimeric cells? This is a nontrivial question, for which a solution has recently been suggested.
microchimerism; cell-based non-invasive prenatal diagnosis; single cell analysis; DNA typing; whole genome amplification; laser microdissection; rare cell analysis
Systemic lupus erythematosus is a chronic autoimmune disease characterized by an abundance of autoantibodies against nuclear antigens. Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PCI-32765 has shown promise in limiting activity of multiple cells types in various models of cancer and autoimmunity. The aim of this study was to determine the effect of Btk inhibition by PCI-32765 on the development of lupus in lupus-prone B6.Sle1 and B6.Sle1.Sle3 mice.
B6.Sle1 or B6.Sle1.Sle3 mice received drinking water containing either the Btk inhibitor PCI-32765 or vehicle for 56 days. Following treatment, mice were examined for clinical and pathological characteristics of lupus. The effect of PCI-32765 on specific cell types was also investigated.
In this study, we report that Btk inhibition dampens humoral autoimmunity in B6.Sle1 monocongenic mice. Moreover, in B6.Sle1.Sle3 bicongenic mice that are prone to severe lupus, Btk inhibition also dampens humoral and cellular autoimmunity, as well as lupus nephritis.
These findings suggest that partial crippling of cell signaling in B cells and antigen presenting cells (APCs) may be a viable alternative to total depletion of these cells as a therapeutic modality for lupus.
It has been observed that patients with systemic lupus erythematosus and discoid
lesions have a milder systemic disease.
To compare the clinical, demographic and autoantibody profile of systemic lupus
erythematosus patients with and without discoid lesions.
We carried out a retrospective study involving 288 systemic lupus erythematosus
patients who met at least four classification criteria of the American College of
Rheumatology for systemic lupus erythematosus, comparing the clinical, serological
and demographic factors between patients with and without discoid manifestations.
Of the 288 patients, 13.8% had discoid lesions. Univariate analysis found no
differences in the prevalence of malar rash, photosensitivity, arthritis,
serositis, leukopenia, lymphopenia and hemolytic anemia or anemia of the central
nervous system (p = ns). Renal lesions were more common in those without discoid
lesions (p =0.016), and hemolysis (p<0.0001) was more common in those with
discoid lesions. Regarding the profile of autoantibodies, only the anti-RNP
antibody was more common in those with discoid events (p =0.04). In a logistic
regression study, only the renal lesions and anti-RNP maintained their
associations with discoid manifestations.
Patients with lesions of systemic lupus erythematosus and discoid lesions have
lower prevalence of renal involvement and a greater presence of anti RNP.
Glomerulonephritis; Lupus erythematosus, cutaneous; Lupus erythematosus, discoid; Lupus erythematosus, systemic
Sera from groups of patient with systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, and progressive systemic sclerosis and normal controls were compared, using different antinuclear antibody assays. Hep-II cells, used as a substrate for the detection of antinuclear antibodies, appeared to be more sensitive than rat liver substrate. In addition, the fluorescent patterns were easier to identify on Hep-II cells. All systemic lupus erythematosus sera with antibodies reactive with kinetoplasts of Crithidia luciliae had binding greater than 43% for single-stranded DNA. Based on the high sensitivity of the Hep-II substrate and the relative specificity of high (greater than 43%) binding for single stranded DNA by sera from patients with systemic lupus erythematosus, it appears that these two tests are most useful in differential diagnosis and for the detection of systemic lupus erythematosus.
Central nervous system (CNS) involvement is a common and important complication in systemic lupus erythematosus. The mechanisms for CNS involvement are poorly understood and reliable diagnostic procedures are lacking. Pairs of serum and cerebrospinal fluid (CSF) specimens from 17 patients with clinical and serological manifestations of systemic lupus erythematosus were analysed. All 11 patients with definite or suspect clinical CNS disorder revealed some kind of abnormality in the CSF, in contrast to three of seven systemic lupus erythematosus patients without CNS disorder. The most prominent findings in systemic lupus erythematosus patients with CNS disorder were immune aberrations with oligoclonal bands on agarose isoelectric focusing (AIF) and elevation of IgG and IgM index, probably reflecting intrathecal production of IgG and IgM respectively. Intrathecal production of antiviral antibodies was found in four of 12 patients by AIF followed by immunofixation and subsequent autoradiography. An enzyme-linked immunoabsorbent assay (ELISA) could not detect autoantibodies against structural brain antigens.
Significant differences in both specificity and avidity of anti-DNA antibodies were observed in the sera of groups of patients with active systemic lupus erythematosus glomerulonephritis, active systemic lupus erythematosus without nephritis, and in IgG eluates obtained by DNAase digestion of isolated glomeruli from glomerulonephritic kidneys. With methylated albumin-kieselguhr fractionated 3H-HeLa DNA as a source of native or single-strand DNA antigen in a modified Farr assay, an increased level of antibody to native DNA was associated with active systemic lupus erythematosus, particularly active nephritis. The avidity of antinative DNA estimated from plots of the reciprocals of bound and free antigen according to the Sips distribution formula was significanly lower in active glomerulonephritis sera than in sera from patients with active systemic lupus erythematosus without nephritis. However, antinative DNA of uniformly high avidity was found in the glomerular eluates. Avidity of single-strand DNA antibodies did not differ in the various patient groups. The data stronly supprot a major role for high avidity antinative-DNA in DNA/antiDNA immune complex-induced glomerular injury in systemic lupus erythematosus.