Lupus Erythematosus Cell Test Research Articles

Lupus Erythematosus Cell Test Magath And Winkle Method: A Diagnostic Test for Systemic Lupus Erythematosus

Lupus Erythematosus (LE) cells were first discovered in 1948 by American clinical hematologists, Malcolm Hargraves and Robert Morton and a laboratory technician, Helen Richmond. Named LE cells because they are typically found in patients with Systemic Lupus Erythematosus (SLE) disease and are one of the antinuclear autoantibodies found in autoimmune diseases. LE cells are easily recognized under a microscope in the form of polymorphonuclear leukocytes (PMNs), usually neutrophils containing a homogeneous mass (LE Body) that is spherical in shape and reddish-purple in color, the nuclear lobes are pushed to one side and thinned, appearing trapped around the LE body. The LE cell test is carried out by destroying leukocyte cells so that they release their nucleoprotein and react with Immunoglobulin (Ig) G and this complex is phagocytized by normal PMN cells that are still present. The LE cell test was first performed to diagnose SLE, but is now rarely used because it has been replaced by a better test, namely the antinuclear antibody test (ANA) to diagnose SLE. However, LE cells are still considered the most important cells by some rheumatologists in the medical world. The LE cell test can be done in several ways, namely: the Magath and Winkle method (a modification of Zimmer and Hargraves), the Zinkham and Conley method, and the Mudrick method. Samples that can be used in the LE Cell test are: Heparinized venous blood, Oxalated venous blood, Defibrinated venous blood, and Clotted venous blood.

Professional Insights from a Pioneer in Autoimmune Disease Testing: The Future of Antinuclear/Anticellular Antibody Testing.

Almost half a century has lapsed since I embarked on a career-long study of systemic autoimmune rheumatic diseases (SARDs)2 with a focus on their autoantibodies directed against an astounding spectrum of cellular antigens (1). The discovery of the lupus erythematosus cell and the development of the lupus erythematosus cell test serves as a historic reference point for the study of antinuclear antibodies (ANAs), or what today international consensus advocated should more correctly be referred to as anticellular antibodies (ACAs) (2, 3). Paralleling the explosion of the spectrum of ACAs was a remarkable transition in the technologies used to detect autoantibodies (1). Although some of the “octogenarian” assays such as double immunodiffusion, hemagglutination, complement fixation, and counterimmunoelectrophoresis are fading into oblivion, the ACA indirect immunofluorescence (IIF) test is increasingly used as a screening test and entry criterion for SARD. However, the emergence of newer multianalyte array technologies that have higher throughput, sensitivity, and specificity and detect a broader range of autoantibodies in comparatively miniscule serum samples may eventually replace the ACA …

The assessment of serum-mediated phagocytosis of necrotic material by polymorphonuclear leukocytes to diagnose and predict the clinical features of systemic lupus erythematosus: an observational longitudinal study.

BackgroundSerum-mediated phagocytosis of antibody- and complement-opsonized necrotic cell material (NCM) by polymorphonuclear leukocytes can be quantified by using a flow cytometry–based assay. The phagocytosis of necrotic cell material (PNC) assay parallels the well-known lupus erythematosus cell test. In this study, we aimed to investigate the diagnostic accuracy of the assay and the relationship with clinical manifestations and disease activity in systemic lupus erythematosus (SLE).MethodsThe diagnostic accuracy for SLE diagnosis of the PNC assay was studied by cross-sectional assessment of blood samples from 148 healthy control subjects and a multicenter rheumatic group (MRG) of 529 patients with different rheumatic symptoms. A cohort of 69 patients with an established SLE diagnosis (SLE cohort) underwent longitudinal clinical and laboratory follow-up for analysis of the temporal relationships between PNC positivity and specific clinical manifestations.ResultsIn 35 of 529 MRG patients, 13 of whom had SLE, the PNC assay result was positive. Combined positivity of the PNC assay and anti–double-stranded DNA antibodies increased specificity and positive predictive value for SLE diagnosis to 0.99 and 0.67, respectively. In the longitudinal study, 42 of 69 SLE cohort patients had positive results in the PNC assay at least once. PNC assay positivity was associated with current hematological manifestations and could predict mucocutaneous manifestations. When combined with hypocomplementemia, PNC positivity preceded increased Systemic Lupus Erythematosus Disease Activity Index 2000 score, glomerulonephritis, and alopecia.ConclusionsSerum-mediated PNC by polymorphonuclear leukocytes is commonly but not exclusively seen in patients with SLE. The PNC assay may be used in follow-up of patients with SLE and, especially in combination with other routinely assessed laboratory tests, may help to predict flares and different clinical manifestations, including glomerulonephritis. Our results encourage further development of the PNC assay as a complementary laboratory tool in management of patients with SLE.

Lupus erythematosus cells in vivo (pleural fluid): An unusual presentation of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes. In earlier times, the diagnosis of SLE included the lupus erythematosus (LE) cell assay. Though the LE cell test has now been declared obsolete, its presence carries importance especially when one finds LE cells in vivo. We report an unusual case of SLE in a 27-year-old female who presented with acute shortness of breath, fever, and cough. On initial outpatient basis investigations, the patient was detected with anemia, bilateral pleural effusion, synovitis, and juxta-articular swelling of the soft tissues. Her chest radiograph effusion was tapped and sent to the cytopathology laboratory. The cytological examination of the pleural fluid revealed numerous LE cells that prompted the diagnosis of SLE. Autoimmune serology techniques such as antinuclear antibody staining have replaced the LE cell assay. However, as presented in this report and found in a review of the literature, the in vivo finding of LE cells by cytopathology can provide an important clue to the diagnosis of SLE. This case is interesting because although pleural effusion is common, very rarely LE Cells are encountered in vivo. There are very few case reports of SLE diagnosed in a cytopathology laboratory. Moreover, our finding of LE cells in the pleural fluid of the patient led to swift diagnosis, helped rule out the differential diagnosis of rheumatoid arthritis and prompted the immediate initiation of treatment. Furthermore, our case highlights the fact that no matter the advances in diagnostic testing methods, practitioners must always keep an eye open for the basic pathognomonic findings of diseases.

Autoantibodies to protein transport and messenger RNA processing pathways: endosomes, lysosomes, Golgi complex, proteasomes, assemblyosomes, exosomes, and GW bodies

Over 50 years ago the lupus erythematosus (LE) cell phenomenon was described and this was quickly followed by the introduction of the LE cell test and indirect immunofluorescence (IIF) to detect antinuclear antibodies (ANA) in clinical laboratories. Recently, attention has turned to the identification of the autoantigens that bind to cytoplasmic organelles such as the Golgi complex, endosomes and other “cytoplasmic somes”. Three endosome autoantigens include early endosome antigen 1 (EEA1, 160 kDa), cytoplasmic linker protein-170 (CLIP-170, 170 kDa), and lysobisphosphatidic acid (LBPA). Antibodies to EEA1 were seen in a variety of conditions but approximately 40% of the patients had a neurological disease. Despite the prominence of lysosomes in cells and tissues, reports of autoantibodies are limited to the lysosomal antigen h-LAMP-2 and the cytoplasmic antineutrophil antibodies (cANCA). Autoantigens in the Golgi complex include giantin/macrogolgin, golgin-245, golgin 160, golgin-97, golgin 95/gm130, and golgin-67. More recently, there has been an interest in autoantibodies that bind components of the “SMN complex” or the “assemblyosome”. Arginine/glycine (RG)-rich domains in components of the SMN complex interact with Sm, like-Sm (LSm), fibrillarin, RNA helicase A (Gu), and coilin proteins, all of which are antigen targets in a variety of diseases. More recently, components of a novel cytoplasmic structure named GW bodies (GWBs) have been identified as targets of human autoantibodies. Components of GWBs include GW182, a unique mRNA-binding protein, like Sm proteins (LSms), and decapping (hDcp1) and exonuclease (Xrn) enzymes. Current evidence suggests that GWBs are involved in the cytoplasmic processing of mRNAs. Autoantibodies to the “cytoplasmic somes” are relatively uncommon and serological tests to detect most of them are not widely available.

'Rhupus' Syndrome

• Occasionally patients with overlapping features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), termed "rhupus," have been encountered. We wanted to ascertain the frequency of such patients and determine whether they represent a unique overlap syndrome. Of approximately 7000 new patients evaluated over 11 years, we identified six patients who had, on the average, 6.7 American Rheumatism Association criteria for RA and 4.2 criteria for SLE. Criteria for RA included chronic symmetric arthritis with morning stiffness (six patients); subcutaneous nodules (two patients); positive rheumatoid factors test (four patients); and radiologic erosions (four patients). The criteria for SLE included malar rash (three patients); discoid lupus erythematosus (two patients); biopsy-proved nephritis (one patient); photosensitivity (one patient); leukopenia/thrombocytopenia (four patients); positive antinuclear antibodies or lupus erythematosus cell test (six patients); hypocomplementemia (two patients); and abnormal results from skin biopsy (two patients). During observations of up to ten years, the conditions of three patients were stable or improved, one died, and two were unavailable for follow-up. Patients usually did not have conditions that evolved to classic rheumatic disease patterns. Rhupus was not common and did not occur more frequently (0.09% prevalence among our patients) than expected from chance concurrence of SLE and RA (calculated at 1.2%). These observations confirm that rhupus indeed exists as a syndrome manifested by patients sharing features of probable coincidental concurrence of RA and SLE, but not as a unique clinical pathologic or immunologic syndrome. Appreciation of these patients with rhupus is important since their therapy and outcome differ from those having RA or SLE alone. (<i>Arch Intern Med</i>1988;148:1633-1636)

Survival in Systemic Lupus Erythematosus-Reply

We agree that there are many improvements in diagnosis and therapy during the years that this study covered and mentioned specifically in the discussion: The notably improved survival rates we have observed may be due to several factors. One may be a generally better understanding of the disease and complications of therapy. Another may be the recent use of newer antibiotics. We do not believe we were diagnosing additional lupus cases because of the use of the antinuclear antibody, C3, or anti-DNA antibodies since all patients in both groups met the American Rheumatism Association's (ARA) Preliminary Criteria for the Diagnosis of SLE, which does not include any of these laboratory tests. Indeed, the lupus erythematosus cell test, which is included in the criteria, was positive in a higher percentage of the New York patients because this test was performed at every clinic visit in New York and was

Antinuclear antibodies in chronic psychotic patients treated with chlorpromazine.

The authors found a significantly higher incidence of antinuclear antibodies (ANA) and positive lupus erythematosus cell tests in chronic psychotic patients who received 400 mg a day or more of chlorpromazine (CPZ) for at least 7 weeks than in those who had taken 50 to 300 mg a day for varying periods or those who had received no CPZ for at least 3 months. Despite the high incidence of ANA, there was no observed development of lupuslike syndrome. The authors suggest that CPZ in high doses may induce ANA in humans.

SLE Latex Test Kit

To the Editor.— Dubois and Strain (225:637, 1973) have presented interesting and useful data on the high selectivity of the Lederle Systemic Lupus Erythematosus (SLE) latex test kit (no false-positives). Their data further suggest a sensitivity of only 19% (21 out of 121 positive tests in patients with SLE). Since the preliminary criteria for the classification of SLE 1 and most other published reports 2,3 indicate lupus erythematosus (LE) cell test positivity of greater than 70% in SLE and Dubois and Strain report only 38.8% (rotary LE cell test), one must inquire whether similar populations are being measured. Do the patients described meet the preliminary criteria for the classification of systemic lupus erythematosus? What is the sensitivity and selectivity of the Lederle test in patient groups with high incidence of positive LE cell tests? Until these questions are answered, the data of Dubois and Strain should not be accepted without

Canine systemic lupus erythematosus. Transmission of serologic abnormalities by cell-free filtrates.

The presence of viruses was sought in a colony of dogs bred from parents with systemic lupus crythematosus (SLE). Cell-free filtrates prepared from the spleens of these animals were injected into newborn dogs, mice, and rats. The canine recipients developed antinuclear antibody (ANA) and positive lupus erythematosus (LE) cell tests: ANA and, in some cases, antinative DNA antibodies were produced by the murine recipients: no abnormalities were detected in the rats. Serial passage of spleen cells or cell-free filtrates of spleen tissue in syngeneic mice reduced the time required for appearance of ANA from 9 to 4 mo. Some murine recipients of the canine filtrate developed malignant lymphomas. Murine leukemia viruses were identified in these tumors by electron microscopic, virologic, and serologic technics. These neoplasms, but not other tumors known to contain murine leukemia viruses, were associated with the production of ANA. Puppies inoculated with the canine filtrate-induced mouse lymphoma developed ANA and positive LE cell tests within 4 mo. THE RESULTS WERE INTERPRETED TO INDICATE THE PRESENCE IN CANINE SLE OF A VIRUS CAPABLE OF: (a) inducing the serologic abnormalities of SLE in normal dogs and mice: (b) activating latent murine leukemia viruses: and (c) spreading by both horizonal and vertical routes.

Endometrial cell imprints as a source of antigen for antinuclear antibody detection.

The indirect immunofluorescent imprint technic and the lupus erythematosus cell test were used to test 700 sera for antinuclear factors. Touch imprints of endometrium were employed as nuclear substrates for the indirect fluorescent antibody procedure. The results obtained were reproducible and reliable. Controls were consistent. Because of an abundant source of material, many slides can be prepared rapidly and stored for varying periods of time. The test procedure, easy to perform and interpret, is economical and less time consuming than the routine lupus erythematosus preparation.

"Lupoid" Hepatitis, a Nonentity in the Spectrum of Chronic Active Liver Disease

The hypothesis that lupoid hepatitis represents a specific entity in the range of chronic active liver diseases was tested by examining the clinical, biochemical, immunochemical, and histologic features of 88 consecutive patients with chronic active liver disease. All patients were selected by predefined criteria and regardless of the result of the lupus erythematosus (LE) test. Initially, the test was positive in 30 patients and negative in 58 patients. LE-positive patients were characterized by disease of shorter duration before symptoms developed and more frequent hepatosplenomegaly; higher levels of serum bilirubin, γ-globulin, and IgG; longer prothrombin time; and lower levels of serum albumin. The incidence of subacute hepatitis with bridging was greater in LE-positive patients. In contrast, the two groups could not be differentiated by sex, age, associated disease of an autoimmune type, most systemic manifestations of liver disease, responses to treatment, the presence of smooth muscle antibody, antinuclear antibody, or Australia antigen, and the degree of plasma cell infiltration on liver biopsy. The LE cell test became negative in 92% of those who responded to treatment, but in none who failed to respond. Discriminant analysis of numerous variables failed to distinguish characteristic features associated with the LE test in most patients. The data are interpreted as showing that a positive LE test indicates more active and severe liver disease rather than a different entity with a specific cause or prognosis.

Pathogenetic mechanisms of interstitial pulmonary fibrosis in patients with serum antinuclear factor: A histologic and clinical correlation

The clinical features and histologie findings in the lung biopsy specimens of six patients with idiopathic interstitial pulmonary fibrosis and serum antinuclear factor are presented. Patients with diseases commonly associated with interstitial pulmonary fibrosis and/or antinuclear factor, such as systemic lupus erythematosus, rheumatoid arthritis or scleroderma, as well as patients with arthritis or positive lupus erythematosus cell tests, were excluded. The histologic changes were characterized by the coexistence of well-established fibrosis in the alveolar walls and/or the peribronchiolovascular tissues and multiple foci of predominantly lymphocytic infiltrates with some plasma cells and eosinophils. The transition from the lymphocytic infiltrates into fibrosis was evident in most of the biopsy specimens, and the presence of lymphoid follicles with germinal center formation was one of the prominent features. These histologic findings, the presence of antinuclear antibodies, the history of preceding virus-like respiratory tract infections in three of the six patients, facial hyperpigmentation in one, discoid lupus lesions of the scalp in another and renal involvement in a third patient, suggest that the pulmonary lesions in these patients resulted from immune reactions to some agents not unlike those seen in systemic lupus erythematosus.

Organized Intraglomerular Deposits in NZB Mouse Disease

Mice of the inbred NZB strain develop a spontaneous disease characterized by autoimmune hemolytic anemia, positive lupus erythematosus cell tests and antinuclear antibodies and nephritis. This disease is analogous to human systemic lupus erythematosus. In ultrastructural studies of the glomerular lesion in NZB mice, intraglomerular dense deposits in mesangial, subepithelial and subendothelial locations were described. In common with the findings in many examples of human and experimental nephritis, including many cases of human lupus nephritis, these deposits were amorphous or slightly granular in appearance with no definable substructure.We have recently observed structured deposits in the glomeruli of NZB mice. They were uncommon and were found in older animals with severe glomerular lesions by morphologic criteria. They were seen most commonly as extracellular elements in subendothelial and mesangial regions. The deposits ranged up to 3 microns in greatest dimension and were often adjacent to deposits of lipid-like round particles of 30 to 250 millimicrons in diameter and with amorphous dense deposits.

Treatment of Lupus Nephritis With Azathioprine

Azathioprine (1.7 to 4.3 mg/kg/day) was administered to 11 patients with nephritis of systemic lupus erythematosus (LE) (positive LE cell test). Prior therapy with prednisone was ineffective, had toxic effects, or both. Sustained improvement in nephritis (hematuria, proteinuria, serum electrolytes, edema) occurred gradually in three patients, transient improvement occurred in two, immunologic improvement occurred in only one patient and five (three uremic) patients were not improved. Four patients died during or shortly after therapy of 7 to 53 days duration. Azathioprine-induced remissions of prednisone-resistant lupus nephritis were infrequent. Some remissions did not occur until after leukopenia and systemic infection had complicated therapy.

Abstracts of Papers Presented at the Third International Complement Workshop, Harvard Medical School, Boston, Massachusetts, June 3–5, 1968

Abstract A 6-year-old child gradually developed systemic lupus erythematosus (SLE). In the first titration 3 months after onset of the disease, a zero C′H50 titer was found, while SLE was not yet manifest. At that time, the lupus erythematosus (LE) cell test was still negative and there were no anti-nuclear factors (ANF) present. Immunoglobulins could not be demonstrated in the basal membrane of the skin. Fluorescence demonstrating immunoglobulin fixation in skin was for the first time positive 5 months after the beginning of the complaints, while the LE cell test and ANF fluorescence remained negative. ANF were first demonstrated at 10 months. The LE cell test remained negative. A C′H50 titer of 0 value was found throughout. Patient's sera were tested for C′1, C′2, C′4 and “C′3 complex” (EDTA serum); only absence of C′1 was consistently noted. The C′1 esterase inhibitor level of the serum was significantly increased varying from 150 to 300% above normal.

Renal disease associated with positive lupus erythematosus tests in a cross-bred strain of mice.

A STRAIN of mice NZB/BL suffering from an autoimmune type of haemolytic anaemia has been described1,2. Since then it has been shown that approximately 4 per cent of this strain have positive lupus erythematosus cell tests and that many of the animals show renal changes resembling those seen in human systemic lupus erythematosus2,3. In this paper it was also shown that F1 and F2 progeny derived from a cross between mice of the NZB/BL and the NZY/BL strains showed a low incidence of haemolytic anaemia but 25 per cent of the animals had positive lupus erythematosus cell tests and all had renal changes resembling lupus nephritis. These animals died from renal failure within 18–24 months of age.

Rheumatoid arthritis, leg ulceration and positive lupus erythematosus cell test: report of a case of successful grafting during cortisone therapy.

Rheumatoid arthritis, leg ulceration and positive lupus erythematosus cell test: report of a case of successful grafting during cortisone therapy.

Latex fixation test and lupus erythematosus cell test; studies on their diagnostic and etiological significance in primary chronic polyarthritis

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study