Frequency Of Positive Test Results Research Articles

The Problem of DNA/RNA Contamination in the Laboratory during PCR Testing for COVID-19

Introduction. When conducting PCR (polymerase chain reaction) testing of biospecimens for SARS-CoV-2 RNA at the beginning of the COVID-19 pandemic, the laboratory service in Russia and foreign countries encountered problems related to the accuracy of diagnostics and obtaining false negative, false positive, and dubious results. The objective of this work was to analyze current literature on the problem of false positive and dubious results of RT-PCR testing for COVID-19. Material and methods. We selected Russian and foreign English-language publications devoted to organization of laboratory diagnostics of the novel coronavirus disease, challenges of PCR testing for SARS and MERS, and general issues of DNA contamination in a PCR laboratory for 2012–2020. We also reviewed current regulations and guidelines for COVID-19 diagnostic testing. Results. The analysis of factors leading to contamination of specimens with nucleic acids in the laboratories performing massive COVID-19 PCR testing during the pandemic showed that the main reasons for contamination included a large number of tests, accumulation of samples in the laboratory, and the increased amount of wastes containing amplification products. Cross-contamination occurs due to technical errors in the course of laboratory manipulations at the stages of sample preparation and inactivation, RNA isolation, and addition of cDNA/RNA or positive control samples to the reaction mixture. Pollution of laboratory working areas with amplicons arising from the opening of tubes and plates containing PCR products is the main cause of total contamination in the laboratory. Signs of cross-contamination include the increase in the proportion of positive samples with low threshold cycle values and detection of a positive signal from negative control samples at RNA isolation and amplification stages. A positive result for all samples in a round, including negative control samples, is a marker of “total contamination” in the laboratory. In addition to contamination, formation of nonspecific PCR products at late reaction cycles and nonspecific fluorescence of the reaction mixture, which occurs when reagent storage temperatures are not observed, may also lead to false positive results. Conclusion. To prevent contamination in a PCR laboratory, strict control over the flow of test samples and medical wastes, regular analysis of the frequency of positive test results, and mandatory laboratory quality control of testing and DNA/RNA contamination are compulsory.

Anaplasma phagocytophilum in domestic cats from Germany, Austria and Switzerland and clinical/laboratory findings in 18 PCR-positive cats (2008-2020).

Anaplasma phagocytophilum is considered the most significant rickettsial pathogen affecting cats. The organism is transmitted by ticks of the species Ixodes ricinus in Central Europe and can cause granulocytic anaplasmosis in pets, wildlife and humans. The aims of this study were to assess the frequency of positive test results for A phagocytophilum in cats in Germany, Austria and Switzerland, as well as to evaluate clinical and laboratory findings in cats with positive PCR results. This study included the results of direct (PCR) and indirect detection methods (immunofluorescence antibody tests [IFAT]) requested by veterinarians in Germany, Austria and Switzerland between 2008 and 2020 from the LABOKLIN laboratory (Bad Kissingen, Germany). The veterinarians treating the PCR-positive cats were contacted by telephone to enquire about their clinical signs, laboratory findings, management and outcomes. In total, 244/1636 cats (15%) tested positive by direct (PCR: n = 27/725 [4%]) and/or indirect detection methods (IFAT: n = 221/956 [23%]). In 18/26 cats with PCR results positive for A phagocytophilum, additional information about clinical signs, laboratory findings, treatment and outcome was obtained. Of these 18 cats, five had comorbidities independent of their infection with A phagocytophilum. The most common clinical signs in PCR-positive cats (total/without comorbidities) were lethargy (83%/92%), fever (83%/85%) and thrombocytopenia (61%/62%). Overall, more than half (57%) of the cats with and without comorbidities recovered clinically. Infections with A phagocytophilum should be considered as differential diagnoses in cats with tick infestation, lethargy, fever and thrombocytopenia. The clinical signs and laboratory findings are consistent with published case reports in cats. Ectoparasite prophylaxis in cats is recommended throughout the entire year.

Sexually Transmitted Disease Testing of Human Immunodeficiency Virus-Infected Men Who Have Sex With Men: Room for Improvement.

In the United States, sexually transmitted infection (STI) testing is recommended at least annually for sexually active men who have sex with men (MSM). We evaluated human immunodeficiency virus (HIV) providers' STI testing practices and frequency of positive test results. We analyzed data from HIV Outpatient Study (HOPS) participants who, from 2007 to 2014, completed a confidential survey about risk behaviors. Using medical records data, we assessed the frequency of gonorrhea, chlamydia, and syphilis testing and positive results during the year after the survey for MSM who reported sex without a condom in the prior 6 months. We compared testing frequency and positivity for men having 1, 2 to 3, and 4 or more sexual partners. Correlates of STI testing were assessed using general linear model to derive relative risks (RR) with associated 95% confidence intervals (CI). Among 719 MSM, testing frequency was 74.5%, 74.3%, and 82.9% for gonorrhea, chlamydia, and syphilis, respectively, and was higher in those men who reported more sexual partners (P < 0.001 for all). In multivariable analysis, testing for gonorrhea was significantly more likely among non-Hispanic black versus white men (RR, 1.17; 95% CI, 1.03-1.33), among men seen in private versus public clinics (RR, 1.16; 95% CI, 1.05-1.28), and among men with 2 to 3 and 4 or more sexual partners versus 1 partner (RR, 1.12; 95% CI, 1.02-1.23, and RR, 1.18; 95% CI, 1.08-1.30, respectively). Correlates of chlamydia and syphilis testing were similar. Test positivity was higher among men with more sexual partners: for gonorrhea 0.0%, 3.0%, and 6.7% for men with 1, 2 to 3, and 4 or more partners, respectively (P < 0.001, syphilis 3.7%, 3.8% and 12.5%, P < 0.001). Among HIV-infected MSM patients in HIV care who reported sex without a condom, subsequent testing was not documented in clinic records during the following year for up to a quarter of patients. Exploring why STI testing did not occur may improve patient care.

Development of a multisystem surveillance database for transfusion-transmitted infections among blood donors in the United States.

The frequency of positive test results for transfusion-transmitted infections (TTIs) among blood donors is an important index of safety; thus, appropriate monitoring is critical, particularly when there are changes in policies affecting donor suitability. Testing algorithms from three large blood systems were reviewed and consensus definitions for a surveillance-positive result for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV) established. In addition, information on each donation, including donor demographics and location, was collected. Combined data were analyzed to characterize the epidemiology of TTIs by person, place, and time. Data from 14.8 million donations were collected for 2011 to 2012, representing more than 50% of the US blood supply. Surveillance-positive rates per 10,000 donations were as follows: HBV, 0.76; HCV, 2.0; HIV, 0.28; and HTLV 0.34. Rates did not vary between the 2 years, although there was variation within a year. With the exception of HTLV, rates were higher among males, and all rates were higher among first-time donations. Window-period donations (those positive only in nucleic acid tests) were infrequent (HBV, 13; HCV, 60; HIV, 14) during the 2-year period. Frequencies of surveillance-positive results varied by donor age and residence location. We demonstrated that standardized data from multiple major US blood systems can be combined and analyzed for change. However, TTI frequencies are low, impacting their sensitivity to change. Furthermore, observed fluctuations in TTI frequencies may be secondary to changes in blood donor demographics rather than necessarily reflecting the immediate impact of policy modification.

Prevalence and Associated Clinical Characteristics of Exercise-Induced ST-Segment Elevation in Lead aVR

BackgroundExercise-induced ST-segment elevation (STE) in lead aVR may be an important indicator of prognostically important coronary artery disease (CAD). However, the prevalence and associated clinical features of exercise-induced STE in lead aVR among consecutive patients referred for exercise stress electrocardiography (ExECG) is unknown.MethodsAll consecutive patients receiving a Bruce protocol ExECG for the diagnosis of CAD at a tertiary care academic center were included over a two-year period. Clinical characteristics, including results of coronary angiography, were compared between patients with and without exercise-induced STE in lead aVR.ResultsAmong 2227 patients undergoing ExECG, exercise-induced STE ≥1.0mm in lead aVR occurred in 3.4% of patients. Patients with STE in lead aVR had significantly lower Duke Treadmill Scores (DTS) (-0.5 vs. 7.0, p<0.01) and a higher frequency of positive test results (60.2% vs. 7.3%, p<0.01). Furthermore, patients with STE in lead aVR were more likely to undergo subsequent cardiac catheterization than those without STE in lead aVR (p<0.01, odds ratio = 4.2).ConclusionsAmong patients referred for ExECG for suspected CAD, exercise-induced STE in lead aVR was associated with a higher risk DTS, an increased likelihood of a positive ExECG, and referral for subsequent coronary angiography. These results suggest that exercise-induced STE in lead aVR may represent a useful ECG feature among patients undergoing ExECG in the risk stratification of patients.

Cloning and expression of candidate allergens from Culicoides obsoletus for diagnosis of insect bite hypersensitivity in horses

Insect bite hypersensitivity (IBH) is an IgE-mediated (Type I) hypersensitivity reaction induced by allergens from biting midges of the Culicoides spp. The aim of the present study was to identify, clone and express recombinant allergens from C. obsoletus, the main species found feeding on horses in the Netherlands, by sequence homology searches on the C. obsoletus specific RNA database, with previously described allergens from C. nubeculosus and C. sonorensis. BLAST searches with these described allergens resulted in similarity hits with 7 genes coding for C. obsoletus allergens. These allergens were expressed as hexahistidine tagged recombinant proteins in E. coli. Allergens were termed Cul o 1–Cul o 7. A maltase (Cul o 1) plus Cul s 1 (maltase of C. sonorensis) were additionally expressed in insect cells using the baculovirus expression system to compare homologous allergens from different species produced with different expression systems in diagnostic in vitro and in vivo tests.We demonstrate that IBH affected horses in the Netherlands show higher IgE levels to Cul o 1 than to Cul s 1, as determined by an IgE ELISA. Furthermore, we show that Cul o 1 produced in E. coli is at least as suitable for in vitro diagnosis of IBH affected horses as Cul o 1 produced in the baculovirus/insect cell expression system.The resulting proteins were evaluated for their ability to discriminate IBH affected and healthy horses by ELISA and intradermal testing. The frequency of positive test results by ELISA within IBH affected horses ranged from 38% to 67% for the different allergens. When results of IgE-binding to Cul o 1–Cul o 7 were combined the test had a sensitivity of 92% and specificity of 85%. The capability of the allergens to induce Type I hypersensitivity reaction in IBH affected horses was demonstrated by an intradermal test.The results show that E. coli expressed recombinant allergens from C. obsoletus are valuable tools to determine the allergen specific sensitisation profile (component resolved diagnosis) in horses with IBH in countries were C. obsoletus is the most abundant species and may facilitate in the development of future immunotherapy.

Using the Rate of Positive High-Risk HPV Test Results for ASC-US Together With the ASC-US/SIL Ratio in Evaluating the Performance of Cytopathologists

We reviewed our experience with 2 indicators of cytopathologist performance: the relative frequency of the interpretations atypical squamous cells of undetermined significance (ASC-US) and squamous intraepithelial lesion (SIL) and the frequency of positive test results for high-risk human papillomavirus (HR-HPV) DNA associated with a cytologic interpretation of ASC-US. Data derived for 9 cytopathologists were reviewed. ASC-US/SIL ranged from 0.99 to 4.02 (mean, 1.77) in 2005 and from 0.82 to 3.68 (mean, 1.81) in 2006. The HR-HPV+ rate for ASC-US ranged from 31.5% to 54.6% for individual cytopathologists (mean, 46.1%) in 2005 and from 29.6% to 61.8% (mean, 45.8%) in 2006. Combined data from both years showed only a slight negative correlation for these 2 variables. Both indicators together provide useful feedback to cytopathologists. We provide a working schema for interpreting perturbations in these indicators to assist in improving the quality of gynecologic cytology interpretations.

Peanut and hazelnut traces in cookies and chocolates: Relationship between analytical results and declaration of food allergens on product labels

Accidental exposure to hazelnut or peanut constitutes a real threat to the health of allergic consumers. Correct information regarding food product ingredients is of paramount importance for the consumer, thereby reducing exposure to food allergens. In this study, 569 cookies and chocolates on the European market were purchased. All products were analysed to determine peanut and hazelnut content, allowing a comparison of the analytical results with information provided on the product label. Compared to cookies, chocolates are more likely to contain undeclared allergens, while, in both food categories, hazelnut traces were detected at higher frequencies than peanut. The presence of a precautionary label was found to be related to a higher frequency of positive test results. The majority of chocolates carrying a precautionary label tested positive for hazelnut, whereas peanut traces were not be detected in 75% of the cookies carrying a precautionary label.

Vergleich der unspezifischen bronchialen Provokation mit Methacholin unter kontrollierter und freier Inhalation

Using controlled breathing patterns during inhalation of drugs is characterized by a high dose reproducibility which may be of advantage for bronchial provocation testing. In this study 30 healthy subjects with an anamnesis of atopy underwent in a randomized cross-over design bronchial provocation testing with methacholine either with the Viasys-Jäger-APS system or with controlled inhalations (AKITA-System) (controlled inhalation volume and flow). Measured was the frequency of positive test results. Positive test results were defined by a 20 % decline of FEV (1) or a 100 % increase of specific airway resistance (sRaw). There were no significant differences in the prevalence of positive test results obtained with both techniques: APS-FEV (1) : 8, AKITA-FEV (1) : 9; APS-sRaw: 18, AKITA-sRaw: 17. More subjects showed a 100 % increase of sRaw as compared to a 20 % decrease of FEV (1), which may be interesting in order to understand differences in the diagnostic information given by both parameters. However, there were some discrepancies: only in 25 of 30 cases (sRaw: 21 of 30 cases) the results (positive or negative) agreed between both techniques. Although the two techniques for bronchial provocation test showed some discrepancies, these data suggest that controlled inhalations may be an alternative to the APS-system.

HER2 Amplification Ratios by Fluorescence In Situ Hybridization and Correlation with Immunohistochemistry in a Cohort of 6556 Breast Cancer Tissues

To analyze HER2 amplification in a large cohort of diagnostic breast cancer specimens, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed on the same specimens with use of Food and Drug Administration—approved products. Procedures were standardized following the manufacturers' recommendations. Of 116,736 IHC specimens, 20% were positive for HER2. In 16,092 FISH specimens, 22.7% showed HER2 amplification. In the subset of 6556 tissues analyzed with IHC and FISH, however, 59% were positive on IHC and 23.6% were amplified on FISH. The increased frequency of positive test results is skewed by more frequent reflex FISH testing. In general, expression and amplification trended together, with the least amplification (4.1%) seen in IHC-negative cases, 7.4% amplification seen in IHC 1+ cases, 23.3% amplification seen in IHC 2+ cases, and 91.7% amplification seen in IHC 3+ cases. When FISH amplification ratios were stratified, the low FISH ratios (2.0-2.2) were most frequently seen in specimens with negative IHC results, high ratios (> 5.0) were seen in IHC 3+ specimens, and intermediate levels of amplification were similar for all levels of IHC. The effect of changing the cutoff point was analyzed: removing cases with a ratio of exactly 2.0 decreased the FISH positivity rate to 22.2% in the combined IHC and FISH cohort. Sequentially moving the cutoff point to 2.2 and 2.5 affected cases at all IHC expression levels. Each change removed approximately 2% from the apparent positivity. This large database provides the distribution frequency of HER2 protein expression and gene amplification in invasive ductal and lobular breast cancer. The relationship between level of HER2 amplification and clinical outcome will require reanalysis of pivotal trial data.

Hematogenous dissemination of lung cancer cells during surgery: quantitative detection by flow cytometry and prognostic significance

Shedding of neoplastic cells into the circulation is an essential event for the hematogenous metastasis of solid tumors. Recently, several studies reported that a high frequency of cancer cells could be detected in the bloodstream during surgery. The intraoperative detection of hematogenous dissemination of cancer cells was able to identify a subset of patients with malignant diseases at high risk for postoperative metastasis and to predict a poor prognosis. In order to evaluate the association between intraoperative dissemination of cancer cells and postsurgical survival of patients with non-small cell lung cancer (NSCLC), we developed a flow cytometric assay for specific detection of lung cancer cells in the blood. The monocyte-enriched population in the blood was separated by a modified Ficoll–Hypaque density centrifugation and then labeled with a combination of monoclonal antibodies specific for CD45, cytokeratin (CK) and two antigens expressed on lung cancer cells (2F7 and S5A). The assay could detect quantitatively lung cancer cells (defined as CD45 −1 CK + 2F7/S5A + cells), with the sensitivity limit of one cancer cell in 10 5 normal leukocytes. The specificity for lung cancer was 97%, which was calculated from the results of healthy subjects (20 cases) and patients affected with benign pulmonary diseases (26 cases) or esophageal cancer (14 cases). Blood samples of 31 NSCLC patients were collected from pulmonary vein during open thoracic surgery. Fifteen of them (48.4%) were found to have positive test results. The average cancer cell counts in these cases were 0.306×10 6/l. Patients under 55 years of age had a significantly higher percentage of positive findings than those over 55 years of age ( P<0.05). The positive rate increased over the stages and lymph node status, but the differences were not statistically significant. Moreover, patients with squamous cell carcinoma at later stages (stages III and IV) had an increased frequency of positive test results than those at earlier stages (stages I and II, P<0.05). In contrast, no such a difference was found in cases with adenocarcinoma. On the basis of 30-months follow-up date, the median survival time and 2-year survival rate for patients with positive and negative findings were 11 vs. 27 months, and 26.7 vs. 62.5%, respectively. There was a statistically significant difference between overall survival curves that favored the patients with negative test results ( P=0.023). Multivariate analysis indicated the stage of disease and the positive test results as two independent factors that affected survival time ( P=0.017 and 0.027). When a comparison was made within the patients at stages III and IV, the presence of cancer cells in blood was associated with a significantly shorter survival. These data indicate that the hematogenous dissemination of lung cancer cells during surgery would be one of the mechanisms of postoperative tumor metastasis. The detection of these cells may help to identify patients with poor prognosis.

Assessment of IgE allergen specificity among latex-allergic health care workers: review of IgE-binding components of various latex extracts.

Allergic reactions to natural rubber latex have increased during the past 10 years, especially in many health care workers who have high exposure to latex allergens both by direct skin contact and by inhalation of latex particles from powdered gloves. Development of satisfactory diagnostic methods to verify the presence of latex allergy in health care workers requires characterization of the immunoreactive proteins in latex products and identification of specific IgE antibodies in sensitized patients. A number of different latex preparations are now available for in vitro evaluations. Utilizing different in vitro methods, this study examines IgE sensitization to components of latex in a selected population of hospital employees, employing a raw natural latex glove extract and various commercial latex extracts. Two hundred hospital employees exposed to latex were evaluated using an allergy history questionnaire. To further identify sensitized patients, two different specific IgE tests and leukocyte histamine release tests were performed using a panel of latex extracts obtained from different manufacturers. Sodium dodecylsulfate polyacrylamide electrophoresis (SDS-PAGE) profiles were obtained. Sera from 34 subjects suspected to be latex-sensitized were IgE immunoblotted to assess the presence of IgE antibodies directed toward specific latex proteins. Thirty-four participants (17%) were considered sensitized to latex by a positive clinical history in conjunction with positive specific IgE tests (18 individuals) and/or positive histamine release tests (26 individuals). Significant extract differences in both the histamine release response profile and the frequency of positive test results were noted in the histamine release test. Significant individual differences in patients' latex epitope-specificity were found by IgE immunoblotting, substantiated by sodium dodecylsulfate polyacrylamide profiles revealing differences in protein band patterns among the various extracts. The IgE immunoblots indicated that the majority of patients reacted to proteins with molecular weights of 14, 21, 30 to 35, and 42 kD; the 30 to 35 kD protein being predominant. Seven subjects (22%) of the 34 considered to be latex-sensitized did not reveal binding of specific IgE in immunoblots. One latex extract (Stallergene) with the widest IgE-reacting protein repertoire identified the majority of subjects (63%) as latex sensitive by leukocyte histamine release and also provided the best quantitative histamine release test results. Only by testing with a combination of latex extracts were all sensitized individuals identified. This study demonstrates that currently several in vitro methods may be necessary to detect IgE sensitization to latex. Latex extracts to be employed in future skin tests must contain a wide epitope repertoire of IgE-binding proteins to identify all latex-sensitized individuals.

Efficacy and gastroprotective effects of tizanidine plus diclofenac versus placebo plus diclofenac in patients with painful muscle spasms

The efficacy and gastroprotective effects of tizanidine plus diclofenac were compared with placebo plus diclofenac in patients with acute local pain syndromes such as low-back pain. This multicenter, double-masked, placebo-controlled, parallel-group study included patients in the Asia-Pacific region who experienced local pain syndromes of recent onset and clinically discernible muscle spasms. Patients received either tizanidine 2 mg twice daily (BID) with diclofenac 50 mg BID or placebo BID with diclofenac 50 mg BID for 7 days. Efficacy variables (pain at rest, at night, on palpation, and during movement; hardness of muscles on palpation; restriction of body movement and disability due to pain; sleep quality; duration of daytime bed rest) and tolerability (including a questionnaire for gastrointestinal adverse effects) were assessed at baseline, and on days 4 and 8. Overall efficacy and tolerability were assessed and a test for occult blood in the stool was performed on day 8. A total of 405 patients were entered into the study in 12 centers in 6 countries; 361 were assessable. Results revealed that the combination of tizanidine with diclofenac was significantly more effective than diclofenac with placebo for most variables. Overall tolerability was better in patients who received tizanidine with diclofenac, although the difference between groups did not reach statistical significance. However, the frequency of gastrointestinal adverse effects was significantly less in patients who received tizanidine plus diclofenac (12%) compared with patients who received placebo plus diclofenac (32%). The frequency of positive test results for occult blood in the stool was 5% in the former group and 11% in the latter group. The combination of tizanidine with diclofenac was more effective and better tolerated than diclofenac alone in patients with local pain syndromes. This study confirms and extends the results of previous studies suggesting increased efficacy and gastroprotective effects of tizanidine when combined with nonsteroidal anti-inflammatory drugs.

Evaluation of feline leukemia virus diagnostic tests available for in-office use by veterinarians

Summary Blood samples from cats were tested for FeLV group-specific antigen by use of an indirect immunojluorescent antibody (ifa) test, elisa, or both. Several elisa kits were evaluated as they would be used in a veterinary clinic, and some elisa kits were compared with an ifa test for agreement of results. Good agreement of results was evident among the commercially available elisa kits; results for most blood samples were clearly negative or decidely positive. Occasionally, test results were equivocal and retesting was necessary to obtain clear interpretation. Negative results are highly reliable, which makes elisa valuable screening tests for FeLV in healthy cats. Results of tests on blood from healthy cats in Alabama indicated positivity rate of 4.0% in 1978 with an ifa test and 4.8% with elisa in 1988 through 1989. Infection rate in sick cats ranged from 11.6 to 35.8%. The frequency of positive test results for FeLV in cats tested at Auburn University decreased from a 5-year average of 27.7% during 1980 through 1984 to a 5-year average of 14.9% during 1986 through 1990; the rate in 1990 was 11.6%.

Association of psychiatric manifestations with antibodies to ribosomal p proteins in systemic lupus erythematosus

purpose: The goal of this study was to determine whether elevated serum levels of antibodies to ribosomal P proteins (anti-P antibodies) are associated with neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE). Additional experiments examined characteristics of these antibodies that might be associated with pathogenicity. patients and methods: A large number of serum samples were collected from patients with SLE, control subjects with other rheumatic diseases, and normal individuals. At the time serum samples were obtained, patients with SLE were categorized according to the presence of psychosis, depression, and other manifestations of central nervous system (CNS) involvement. Serum anti-P antibody activity was quantitated by an enzyme-linked immunosorbent assay utilizing a synthetic peptide corresponding to the major P protein epitope. results: In a group of 79 normal individuals, mean (± SE) IgG anti-P activity was 0.01 ± 0.003 and no individuals had values greater than 3 SD above the mean. Similar results were obtained measuring IgM anti-P activity. Normal levels were found in all sera from 21 patients with rheumatoid arthritis. Of 119 patients demonstrating various patterns of antinuclear and anticytoplasmic antibody activity, elevated anti-P levels were found only in patients with SLE. Overall, 19% of 269 patients with SLE demonstrated elevated levels of IgG or IgM anti-P antibodies, including 14% of 187 patients without and 29% of 82 patients with neuropsychiatric manifestations. The frequency of positive test results varied greatly depending on the nature of the CNS involvement. The frequency in patients with severe depression (n = 8) and psychosis (n = 29) was 88% and 45%, respectively, compared with only 9% in patients with nonpsychiatric neurologic disease (n = 45). For the entire SLE group, the odds ratio for the association of anti-P antibodies and severe psychiatric manifestations was 7.63 with a 95% confidence interval of 3.61 to 16.14. In a review of 187 patients with SLE originally classified as not having severe psychiatric disease, seven of 10 patients being treated with antidepressant medications had elevated levels of anti-P antibodies. In serial studies, the serum level of anti-P antibodies appeared to correlate with the activity of psychiatric disease and did not correlate with the activity of other manifestations of SLE. Anti-P antibodies in nearly all patients were IgG and directed primarily to the C-terminal 11 amino acids of the P protein. No difference in these characteristics was observed when patients with and without psychiatric manifestations were compared. Paired serum and cerebrospinal fluid (CSF) samples were also obtained from eight patients with active neuropsychiatric disease. Even when expressed as a fraction of the total IgG present, anti-P activity was markedly lower in CSF than in serum. conclusions: Elevated levels of autoantibodies to the C-terminal region of ribosomal P proteins appear to be a specific marker for SLE, and are associated with both severe depression and psychosis in this disease. This assay is easily reproducible and may help distinguish SLE-induced psychiatric disease from that caused by other processes.