Antigen In Cerebrospinal Fluid Research Articles

Changes in a CSF antigen associated with dementia.

An 85-kDa antigen was detected in cerebrospinal fluid (CSF) using a monoclonal antibody, 11.57, raised against a fraction of paired helical filaments extracted from Alzheimer's disease (AD) brain tissues. The antigen is a thermostable protein that is unrelated either to tau or amyloid beta-protein precursor. Its level was measured in lumbar and post-mortem CSF samples and found to be decreased significantly in patients with dementia as compared with non-demented controls. There was no difference in its level between patients with AD and those with non-Alzheimer type dementia. In AD, however, there was a significant relationship between disease progression and the amount of the 85-kDa antigen.

Evaluation of new monoclonal antibody-based latex agglutination test for detection of cryptococcal polysaccharide antigen in serum and cerebrospinal fluid

We evaluated the performance of CRYPTO-LEX (Trinity Laboratories, Inc., Raleigh, N. C.), a new mouse immunoglobulin M monoclonal antibody latex agglutination reagent which reacts with the capsular polysaccharide of the four serogroups of Cryptococcus neoformans. This test was compared with CALAS (Meridian Diagnostics, Cincinnati, Ohio) for the ability to detect cryptococcal antigen in serum and cerebrospinal fluid (CSF). A total of 580 clinical specimens (327 serum and 253 CSF samples), primarily from human immunodeficiency virus-infected patients, were tested in this study. Sixty-seven specimens (44 serum and 23 CSF samples) were positive for cryptococcal antigen with both tests, and 511 (282 serum and 229 CSF samples) were negative. The two latex reagents agreed for 326 of 327 serum specimens (44 positives and 282 negatives). One serum specimen with a titer of 1:2 was CALAS positive but CRYPTO-LEX negative. The titer correlation coefficient for the two tests was 0.884 when two highly discordant serum specimens were eliminated from analysis of the data. The two latex tests agreed for 252 of 253 CSF specimens (23 positives and 229 negatives). One specimen with a titer of 1:2 was positive with CALAS and negative by CRYPTO-LEX. The correlation coefficient of the two tests for CSF titers was 0.886. The sensitivity and specificity of CRYPTO-LEX were 97 and 100%, respectively, with a 99.6% correlation with CALAS. These data show that the performance of CRYPTO-LEX is comparable to that of CALAS for detection of cryptococcal antigen in serum and CSF.

The Effects of Nonclassic Pediatric Bacterial Pathogens on the Usefulness of the Directigen Latex Agglutination Test

Haemophilus influenzae type b, Escherichia coli, Neisseria meningitis, Streptococcus agalactiae, and Streptococcus pneumoniae are classically the predominant meningeal pathogens of children. The Directigen latex agglutination test identifies these pathogens by detecting specific antigens in cerebrospinal fluid (CSF) and urine. The authors tested 1151 specimens from 791 children with suspected meningeal infections. They found that the sensitivity of the Directigen test for detecting the five classic CSF pathogens of children was 83.3% with CSF and 60% with urine specimens. In detecting all pathogens, however, the sensitivity was only 50% with CSF and 37.5% with urine. Thus, an increased prevalence of nonclassic pathogens in a pediatric population adversely affects the efficacy of the Directigen test for confirming a diagnosis of meningitis and emphasizes the diagnostic importance of the clinical history and other routine CSF tests.

Herpes Simplex Encephalitis in a Pregnant Woman: Successful Outcome for the Mother and her Baby

Herpes Simplex Encephalitis in a Pregnant Woman: Successful Outcome for the Mother and her Baby

Cerebrospinal Fluid lnterleukin-6, Prostaglandin E2 and Autoantibodies in Patients with Neuropsychiatric Systemic Lupus Erythematosus and Central Nervous System Infections

Cerebrospinal fluid (CSF) from patients with a variety of central nervous system (CNS) disorders was assayed for cytokines, prostaglandins, and autoantibodies. CSF interleukin-6 (IL-6) in patients with CNS infection (374.24 +/- 92.61 pg/mL) and neuropsychiatric systemic lupus erythematosus (NP-SLE) (71.40 +/- 5.89 pg/mL) were significantly higher than in patients with CNS inflammation (33.92 +/- 29.36 pg/mL) or controls (non-inflammatory CNS diseases) (4.35 +/- 3.00 pg/mL). Interleukin-1 beta, interferon alpha, and tumor necrosis factor alpha were undetectable in these samples: CSF prostaglandin E2 (PGE2) also exhibited similar patterns as IL-6. CSF immunoglobulin G (IgG) in patients with NP-SLE (8.84 +/- 1.80 mg/dL) was much higher than in patients with CNS infection (4.65 +/- 3.09 mg/dL), CNS inflammation (2.54 +/- 1.24 mg/dL), or controls (2.11 +/- 1.03 mg/dL). CSF autoantibodies against calf thymus antigens were present in patients with NP-SLE but not in patients with CNS infection as demonstrated by immunoblot. These results suggest that high IL-6 and PGE2 in CSF favors the diagnosis of CNS infection, while modestly elevated IL-6, high IgG, and autoantibodies against calf thymus antigens in CSF are the features of NP-SLE.

Diagnosis of tuberculous meningitis by detection of immunoglobulin G antibodies to purified protein derivative and lipoarabinomannan antigen in cerebrospinal fluid

Enzyme-linked immunosorbent assay of immunoglobulin G (IgG) activity in cerebrospinal fluid (CSF) and sera was conducted prospectively in 27 patients with tuberculous meningitis (TBM) by using purified protein derivative (PPD) and lipoarabinomannan (LAM) antigens, from January 1989 to August 1990. 29 patients with aseptic meningitis and 49 patients with non-inflammatory neurological illnesses served as controls. All patients had a computed tomography (CT) scan of the head before a lumbar puncture. The IgG antibodies to the antigens were significantly elevated in TBM, and the reactivity was more frequently positive in the CSF than in the sera, suggesting a local synthesis of IgG in the central nervous system (CNS). The sensitivity and the specificity for the diagnosis of TBM were 59.2% and 93.9% for PPD antigen, and 85.2% and 95.9% for LAM antigen, respectively. Assay of IgG reactivity to LAM antigen was clinically very useful for the early diagnosis of TBM and was superior to PPD for detecting the serological evidence of TBM.

Eosinophilic pleocytosis in coccidioidal meningitis: Frequency and significance

purpose: Coccidioidal meningitis (CM) is a major source of. morbidity and mortality in endemic regions. The diagnosis of CM is a clinical challenge. Eosinophilic pleocytosis (EP) is an uncommon finding and present in a relatively limited number of conditions. In order to determine the frequency and the prognostic significance of EP in CM, we conducted the present study. patients and methods: Retrospective chart review of all patients diagnosed as having CM between 1986 and 1991 at Kern Medical Center. All patients had clinical and cerebrospinal fluid (CSF) findings confirmatory of CM. results: Nineteen patients (70%) in the study group had EP, and of these, 8 patients (30%) met the criteria for eosinophilic meningitis (greater than or equal to 10 eosinophils/mm 3). No correlation was found between EP and age, sex, race, results of complement fixation test for coccidioidal antigen in CSF or serum, peripheral eosinophilia, or outcome. conclusion: The presence of EP is a frequent observation in CM. Although we did not demonstrate any prognostic correlation with EP, this finding is of major diagnostic significance and its presence should bring attention to the diagnosis of CM.

Laboratory diagnosis of bacterial meningitis.

Bacterial meningitis is relatively common, can progress rapidly, and can result in death or permanent debilitation. This infection justifiably elicits strong emotional reactions and, hopefully, immediate medical intervention. This review is a brief presentation of the pathogenesis of bacterial meningitis and a review of current knowledge, literature, and recommendations on the subject of laboratory diagnosis of bacterial meningitis. Those who work in clinical microbiology laboratories should be familiar with the tests used in detecting bacteria and bacterial antigens in cerebrospinal fluid (CSF) and should always have the utmost appreciation for the fact that results of such tests must always be reported immediately. Academic and practical aspects of the laboratory diagnosis of bacterial meningitis presented in this review include the following: anatomy of the meninges; pathogenesis; changes in the composition of CSF; etiological agents; processing CSF; microscopic examination of CSF; culturing CSF; methods of detecting bacterial antigens and bacterial components in CSF (counter-immunoelectrophoresis, coagglutination, latex agglutination, enzyme-linked immunosorbent assay, Limulus amebocyte lysate assay, and gas-liquid chromatography); use of the polymerase chain reaction; and practical considerations for testing CSF for bacterial antigens.

Diagnosis of Trypanosoma brucei gambiense sleeping sickness using an antigen detection enzyme-linked immunosorbent assay

A monoclonal antibody-based enzyme-linked immunosorbent assay (antigen elisa) developed for detection of trypanosome antigens in the serum and cerebrospinal fluid (CSF) of patients as a means for diagnosis of Trypanosoma brucei gambiense sleeping sickness was evaluated at the Bureau Central de la Trypanosomiase, Kinshasa, Zaire. Sixty-nine (89·6%) of 77 parasitologically confirmed cases examined at the Daloa clinic had antigens in serum; 35 (45·5%) had antigens in CSF and, in 4 of these, the antigens were detected in CSF only. Taking the serum and CSF results together, 73 (94·8%) of the 77 patients were positive in the assay. In the Kinshasa series, 168 (89·4%) of 188 parasitologically confirmed cases were positive by antigen elisa. The controls, who included 165 blood donors and 40 patients with malaria, 2 with hydatidosis and 12 with leishmaniasis, were negative by antigen elisa. Analysis of CSF results for 35 patients who had antigens in CSF revealed that 34 (97·1%) had elevated CSF white cell counts, 29 (82·9%) had elevated protein levels, and 23 (65·7%) had trypanosomes in their CSF. Moreover, analysis of results for 34 patients whose CSF had been shown to harbour trypanosomes by the double centrifugation technique showed that 24 (70·6%) had antigens in CSF, 28 (82·6%) had elevated protein levels, and 33 (97·1%) had elevated CSF white cell counts. Antigens were rapidly cleared from peripheral circulation following institution of treatment. Antigen clearance was accompanied by a rapid fall in CSF protein levels and white cell counts. These results demonstrate the potential of antigen elisa, not only as a tool for diagnosis, but also for clinical staging and treatment follow-up of patients with T. b. gambiense sleeping sickness.

Detection of Mycobacterium tuberculosis Antigen 5 in Cerebrospinal Fluid by Inhibition ELISA and Its Diagnostic Potential in Tuberculous Meningitis

Inhibition ELISA was used to quantitate Mycobacterium tuberculosis antigen 5 in cerebrospinal fluid (CSF) specimens of 40 patients with a clinical diagnosis of tuberculous meningitis. In all 10 culture-proven patients, the assay was positive; in 30 culture-negative patients, the assay yielded positive results for 21. CSF antigen 5 concentrations ranged from 9 to 82 ng/ml (mean +/- SD, 45.5 +/- 6.2). In 40 patients with nontuberculous neurologic diseases, mean concentration was 1.45 ng/ml. Thus, inhibition ELISA for the detection of M. tuberculosis antigen 5 in CSF has definite diagnostic potential during the active phase of the disease and should be a routine diagnostic test, particularly when bacteriologic cultures in CSF are negative for M. tuberculosis.

Neisseria lactamica Meningitis Following Skull Trauma

A woman developed meningitis due to Neisseria lactamica in association with a cribriform plate fracture. Cerebrospinal fluid antigen tests for Neisseria meningitidis were negative. The patient recovered with intravenous penicillin therapy. N. lactamica can be rapidly distinguished from N. meningitidis by the hydrolysis of ONPG (o-nitrophenyl-beta-D-galactopyranoside). In contrast to N. meningitidis and Neisseria gonorrhoeae, N. lactamica lacks virulence properties. As 100% of N. lactamica strains are susceptible to penicillin and all three previously described patients with N. lactamica meningitis have recovered with penicillin treatment, the reason for distinguishing the organisms in this context is primarily to prevent unnecessary anxiety and prophylaxis among contacts.

Diagnosis of tuberculous meningitis by enzyme-linked immunosorbent assay to detect mycobacterial antigen and antibody in cerebrospinal fluid

Enzymed-linked immunosorbent assay (ELISA) was used to detect mycobacterial antigen and antimycobacterial antibody in cerebrospinal fluid (CSF) specimens of 50 patients with tuberculous meningitis (TBM) and 50 patients with non-tuberculous neurological diseases (control group). The assay gave no false negative results in 10 culture-positive patients with TBM. Detection of mycobacterial antigen in CSF is more sensitive and specific for the diagnosis of TBM than detection of antibody, ELISA should be considered as one of the alternative methods in the laboratory diagnosis of TBM, particularly in culture-negative patients with TBM.

Detection and characterisation of circulating cysticercal antigens in human cerebrospinal fluid

With biotin labelled and unlabelled immunoglobulin fraction of anticysticercal antibodies raised in rabbits, tandem-enzyme linked immunosorbent assay (T-ELISA), capture-dot immunobinding assay (C-DIA) and reverse passive haemagglutination (RPHA) tests were developed for the detection of cysticercal antigens. The sensitivity levels were respectively, 9 ng ml −1, 2 ng ml −1 and 45 ng ml −1. All three methods were of equal specificity as none of the antigens of Mycobacterium tuberculosis, Japanese encephalitis virus and Echinococcus granulosus reacted with anticysticercal IgG. Cysticercal antigens were detected in the cerebrospinal fluid (CSF) of confirmed neurocysticercosis at sensitivity levels of 91·6% by T-ELISA, 83·33% by C-DIA and 75% by RPHA and specificity levels of >93%. Western analysis of these antigens in CSF showed mainly antigens of 64–68 kDa and 24–28 kDA. By crossed immunoelectrophoresis (CIE) with an intermediate gel technique, five circulating antigens were found to be released from scolex and fluid.

Correlation between culture of Mycobacterium tuberculosis and detection of mycobacterial antigens in cerebrospinal fluid of patients with tuberculous meningitis

A retrospective study was done to correlate culture of Mycobacterium tuberculosis and detection of mycobacterial antigen in cerebrospinal fluid (CSF) by an inhibition enzyme-linked immunosorbent assay (ELISA). M. tuberculosis was cultured from CSF of 14 out of 70 patients with a clinical diagnosis of tuberculous meningitis (TBM). Mycobacterial antigens were demonstrated in CSF specimens by inhibition ELISA in all 14 culture-positive patients with antigen concentrations of 14.5-295 ng/ml (mean 158.8 ng/ml). Thus there was positive correlation between the detection of mycobacterial antigen and isolation of M. tuberculosis. Based on this observation, 56 CSF specimens from culture-negative patients with clinically diagnosed TBM were examined for mycobacterial antigen and the data were compared with those from culture positive patients. ELISA gave positive results in 38 specimens, with antigen levels of 12.5-280 ng/ml (mean 152.6 ng/ml). In 70 CSF specimens from patients with non-tuberculous neurological disease (control group), ELISA results were negative. Thus, detection of mycobacterial antigen in CSF specimens by inhibition ELISA had a specificity of 100% and a sensitivity of 67.8% for the diagnosis of TBM and is of potential value in the laboratory diagnosis of TBM.

Detection of mycobacterial antigen in cerebrospinal fluid: diagnostic and prognostic significance

Inhibition enzyme-linked immunosorbent assay (ELISA) was standardised to quantitate circulating mycobacterial antigens in cerebrospinal fluid (CSF) specimens. Of the 40 patients with clinical diagnosis of tuberculous meningitis, the assay was found to be positive in 26 patients. In a control group of 42 patients with non-tuberculous neurological diseases the assay was negative. The assay showed a sensitivity of 65 and 100% specificity for tuberculous meningitis. In 8 patients with tuberculous meningitis receiving chemotherapy, multiple CSF examinations were subjected to this assay. The antigen concentration showed a gradual decrease between 3 and 4 weeks after the commencement of antituberculosis chemotherapy. There was a positive correlation between clinical recovery and antigen concentration. Detection of mycobacterial antigen in CSF specimen by inhibition ELISA has not only diagnostic utility but also could be applied to monitor antituberculosis chemotherapy in patients with tuberculous meningitis. The assay is reproducible and feasible for routine immunology laboratory. It also could be considered as a diagnostic aid when repeated bacteriological cultures are negative in CSF specimens of patients with tuberculous meningitis.

Shedding of CD9 antigen into cerebrospinal fluid by acute lymphoblastic leukemia cells

The accurate identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of acute lymphoblastic leukemia (ALL). We demonstrated that soluble CD9 antigen was shed into CSF obtained from children with ALL, using enzyme-linked immunosorbent assay (ELISA), which used the activity of CD9 antigen to bind the Ricinus communis agglutinin (RCA1) and a monoclonal antibody, SJ-9A4, simultaneously. Using RCA1/SJ-9A4 ELISA, CD9 antigen was detectable in CSF but not in plasma from 12 cases of CD9+ ALL in central nervous system (CNS) relapse. However, CD9 antigen was not released into CSF from 11 cases of CD9- ALL with CNS involvement, 136 cases of CD9+ ALL in complete remission (CR), 29 cases of CD9- ALL in CR, or 21 cases of aseptic meningitis. Interestingly, the levels of CD9 antigen were elevated in CSF from 7 of 10 CD9+ ALL patients without cytologically proven CNS involvement at diagnosis, with subsequent return to undetectable levels after initial induction chemotherapy was begun. In addition, sequential analysis of CSF from a 5-year-old boy with CD9+ ALL in CNS relapse showed that levels of CD9 antigen correlated well with the number of leukemic cells in CSF. Serial quantitative analysis of CD9 antigen in CSF could be useful to detect the proliferation of residual leukemic cells before the clinical manifestation.

Shedding of CD9 Antigen Into Cerebrospinal Fluid by Acute Lymphoblastic Leukemia Cells

The accurate identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of acute lymphoblastic leukemia (ALL). We demonstrated that soluble CD9 antigen was shed into CSF obtained from children with ALL, using enzyme-linked immunosorbent assay (ELISA), which used the activity of CD9 antigen to bind the Ricinus communis agglutinin (RCA1) and a monoclonal antibody, SJ-9A4, simultaneously. Using RCA1/SJ-9A4 ELISA, CD9 antigen was detectable in CSF but not in plasma from 12 cases of CD9+ ALL in central nervous system (CNS) relapse. However, CD9 antigen was not released into CSF from 11 cases of CD9- ALL with CNS involvement, 136 cases of CD9+ ALL in complete remission (CR), 29 cases of CD9- ALL in CR, or 21 cases of aseptic meningitis. Interestingly, the levels of CD9 antigen were elevated in CSF from 7 of 10 CD9+ ALL patients without cytologically proven CNS involvement at diagnosis, with subsequent return to undetectable levels after initial induction chemotherapy was begun. In addition, sequential analysis of CSF from a 5-year-old boy with CD9+ ALL in CNS relapse showed that levels of CD9 antigen correlated well with the number of leukemic cells in CSF. Serial quantitative analysis of CD9 antigen in CSF could be useful to detect the proliferation of residual leukemic cells before the clinical manifestation.

Throat culture from patients with meningococcal meningitis.

Abstract : Throat culture from patients with meningococcal meningitis: Cartwright and Jones suggest that throat culture can be useful in the diagnosis of meningococcal meningitis when the patients have taken antibiotics before admission into hospital. This approach seems valid in the light of the inability of most of the antibiotics that are used for the treatment of meningococcal infections to serve as prophylactic agents. We performed throat cultures on various populations in Cairo, Egypt, where group A meningococcal disease in endemic. Most cases occur in school-age children, a population that we found had a 3.8% carrier rate. Only one of the 58 patients positive by culture of cerebrospinal fluid for agents other than Neisseria was a group A meningococci carrier. Group A meningococci, however, were isolated from 55% of 380 patients who were culture positive for this organism and from 30% of 46 patients who were culture negative but shown to have meningococcal meningitis by stain and detection of specific antigen in cerebrospinal fluid.

Cerebral Granuloma and Meningitis Caused by Candida albicans: Useful Monitoring of Mannan Antigen in Cerebrospinal Fluid

Abstract The authors report the case of a previously healthy patient who had recurrent cerebral granulomas and meningitis caused by Candida albicans 15 years after the first onset. A combination of external drainage of cerebrospinal fluid (CSF) and intraventricular and intravenous chemotherapy with antifungal agents resulted in a favorable outcome. Investigation of this patient revealed no immunological dysfunction, lymphoproliferative disorder, or candidicidal defect of peripheral blood leukocytes. Sequential measurement of Candida mannan antigen in CSF was useful for establishing the early diagnosis of cerebral candidiasis and for judging the effect of our antifungal chemotherapy. In determining the surgical indications and timing of placement of a ventriculoperitoneal or ventriculoatrial shunt for meningitis subsequent to hydrocephalus after candidal infection, it is better to confirm normal concentrations of the mannan antigen in the CSF repeatedly for more than a week and to determine that cultures of the CSF are negative for Candida albicans.

Cerebral granuloma and meningitis caused by Candida albicans

The authors report the case of a previously healthy patient who had recurrent cerebral granulomas and meningitis caused by Candida albicans 15 years after the first onset. A combination of external drainage of cerebrospinal fluid (CSF) and intraventricular and intravenous chemotherapy with antifungal agents resulted in a favorable outcome. Investigation of this patient revealed no immunological dysfunction, lymphoproliferative disorder, or candidicidal defect of peripheral blood leukocytes. Sequential measurement of Candida mannan antigen in CSF was useful for establishing the early diagnosis of cerebral candidiasis and for judging the effect of our antifungal chemotherapy. In determining the surgical indications and timing of placement of a ventriculoperitoneal or ventriculoatrial shunt for meningitis subsequent to hydrocephalus after candidal infection, it is better to confirm normal concentrations of the mannan antigen in the CSF repeatedly for more than a week and to determine that cultures of the CSF are negative for Candida albicans.