CSF: diagnosis of neurosyphilis in a patient hospitalized for an acute brain stroke

We report the case of a sixty-eight years old patient, who was admitted to the emergency for paresthesis associated with dysarthra and speech complaints. Neuroimaging revealed the presence of stenosis caused by arteritis. The notion of history of syphilis infection led to diagnosis of neurosyphilis. Diagnosis is difficult due to its clinical polymorphism and requires using several tests in the cerebrospinal fluid (CSF) because infection involving the central nervous system. Neurosyphilis is diagnosed by finding elevated cell count (80 leukocytes/mm3), high protein level (1.07 g/L) and positive IgG oligoclonal bands. In addition CSF and blood should be titrated with the VDRL and TPHA tests which are difficult to interpret. The diagnosis of active neuro-syphilis requires positive, non specific and specific inflammatory tests.     

Neurosyphilis in HIV-infected patients

To determine the prevalence and the clinical and serological findings of neurosyphilis in HIV-infected patients,Treponema pallidum hemagglutination (TPHA) tests, CD4+ lymphocyte counts and determination of rapid plasma reagin (RPR) titers were performed in 972 HIV-infected patients over a period of 3.5 years. Patients were scored according to the Centers for Disease Control's classification for HIV infection. Reactive serum syphilis tests and positive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) tests, with or without clinical symptoms, were used as the criteria for diagnosis of neurosyphilis. The TPHA test was positive in 31 patients, representing 3.1 % of all HIV-infected patients included in the study. Of these, 13 were intravenous drug addicts, 14 were homosexuals and 4 were heterosexuals. Diagnosis of syphilis was concurrent with HIV infection in 19 patients, prior to HIV infection in 6 patients and after HIV infection in 6 patients. CSF examinations were performed in 28 of the 31 (90.3 %) patients with serologically evident syphilis. Four patients had positive CSF-VDRL tests with pleocytosis (23.5 % of untreated syphilis patients in whom CSF was examined), three of whom reported mild headache, which was considered a doubtful manifestation of neurosyphilis. Patients with syphilis diagnosed and treated prior to diagnosis of HIV infection did not have evidence of neurosyphilis. Seven patients had pleocytosis with a negative CSF-VDRL test, without any clinical manifestations of neurosyphilis. There was no significant difference in the mean CD4+ lymphocyte count between patients with and without neurosyphilis (p=0.5). RPR titers in neurosyphilis patients were greater than those in patients previously treated for syphilis and in those with pleocytosis only (p=0.046 and 0.036, respectively). All neurosyphilis patients had an RPR titer > 18. After therapy, neurosyphilis patients had negative CSF-VDRL tests with a lower level of pleocytosis. The prevalence of neurosyphilis was 0.4% in HIV-infected patients and 23.5% in HIV-infected patients with untreated syphilis. This high prevalence of neurosyphilis warrants CSF examination in HIV-infected patients with syphilis, regardless of the stage of syhilis.     

West Nile virus immunoglobulin A (WNV IgA) detection in cerebrospinal fluid in relation to WNV IgG and IgM reactivity.

BACKGROUND: Diagnostic criteria for neurologic involvement in WNV infection include WNV IgM detection in CSF; however, WNV IgM can persist in CSF >6 months. CSF IgA characterizes other flavivirus infections, but WNV IgA in CSF has not been evaluated. WNV IgM in CSF correlates with IgM in serum but the presence of WNV IgA in CSF compared to serum is unknown. OBJECTIVES: Evaluate WNV IgA detection in CSF as a marker of WNV neuroinvasive infection, initially with samples pre-selected based on WNV IgG and IgM reactivity and subsequently with all available CSF samples submitted for WNV antibody testing over an entire WNV season. STUDY DESIGN: Selected CSF samples and CSF/serum pairs previously tested for WNV IgG and IgM were assayed for WNV IgA. Subsequently, all available CSF samples tested for WNV antibodies during the 2005 season were tested for WNV IgA, including those where paired sera were available and tested for IgA, IgG and IgM. RESULTS: For most samples, including paired CSF and serum, the IgA result qualitatively agreed with the IgM result, regardless of the IgG result. CONCLUSION: IgA detection is equivalent to IgM detection as a marker of WNV infection in CSF.     

ELISA检测梅毒IgM抗体在早期梅毒诊断中的应用

为探讨ELISA法检测梅毒螺旋体IgM抗体（Tp-IgM)在早期梅毒诊断中的意义。本文对确诊的67例早期梅毒、3例早期神经梅毒,3例不定期潜伏梅毒患者与26名非梅毒对照。采用ELISA方法,进行血清/脑脊液的梅毒螺旋体IgM抗体检测,同时作RPR及TPPA检测,结果表明,ELISA,RPR及TPPA的特异性分别为100%、88.5%和100%;ELISA法对于早期梅毒的敏感性（95.5%)高于RPR和TPPA（均为83.6%),而在3例不定期潜伏梅毒血清和3例早期神经梅毒脑脊液中,ELISA各检出2例阳性,提示ELISA法检测Tp-IgM对早期梅毒的诊断价值优于RPR和TPPA,对早期神经梅毒和不定期潜伏梅毒的诊断不具优势。     

IgM, IgA and IgG producing cells in cerebrospinal fluid and peripheral blood in multiple sclerosis.

The protein A plaque assay was used to enumerate IgM, IgA and IgG producing cells per 20 X 10(3) lymphocytes in cerebrospinal fluid (CSF) and peripheral blood (PB) from 37 patients with multiple sclerosis (MS) and in PB from healthy controls. Fifty-seven percent of the MS patients displayed in CSF cells producing IgM, 70% IgA and 89% IgG. IgM or IgA producing cells predominated in CSF from 10 patients, IgG in 27. Immunoglobulin producing cells were often present when the corresponding CSF Ig index was normal, confirming that enumeration of Ig producing cells is a more sensitive variable of the intrathecal immune status. No Ig producing cells were found in CSF from four patients with tension headache, indicating absence of intrathecal Ig synthesis in healthy individuals. The patients with MS had higher numbers of IgM, IgA and IgG producing cells in PB than healthy controls, confirming occurrence of an extrathecal B cell response in MS. Active and stable MS patients did not differ regarding Ig producing cells in CSF nor in PB, which speaks in favour of continuous immune activity within as well as outside the CNS independent of clinical symptoms.     

Serodiagnosis of smear and culture-negative neurotuberculosis with enzyme linked immunosorbent assay for anti A-60 immunoglobulins

Early diagnosis of neurotuberculosis (NTB), useful in prevention of mortality and morbidity, remains a challenge despite availability of several tests. An ELISA test to detect IgG and IgM antibodies against Mycobacterial antigen A-60 (Anda Biologicals, France) was done in 677 specimens; group 1 (NTB): 373 sera and 167 cerebrospinal fluid (CSF), group 2: 100 sera from healthy subjects, group 3: 17 CSF from patients undergoing neurosurgical operations for non-tubercular diseases. Anti-A 60 IgA estimation was done in 99 sera from group 1 and all 100 from group 2. Working dilutions were 1:200 for serum and 1:10 for CSF. Serum IgM and IgG anti-A 60 antibodies were more often detected in group 1 than in 2 (50% Vs 10%, p<.001). Anti-IgG and IgM antibody were detected more often in group 1 than in group 3 (33% Vs 6%, p<.001). In serum and CSF both IgM positivity was more than IgG in 2 subgroups of NTB and these are tubercular meningitis, spinal tuberculosis whereas in tuberculoma IgG positivity was more as compared to other 2 groups. Sera were more often positive than CSF (50% Vs 33%, p<.001). Of 32 patients, in whom magnetic resonance imaging (MRI) was done, 15/18 (83%) patients with suggestive findings in MRI had a positive ELISA (IgG or IgM). AntiA-60 antibody is a useful aid in the diagnosis of NTB, especially in smear and culture negative NTB where one does not have much diagnostic opportunities to choose from.     

Origin of immunoglobulins in respiratory tract secretion and saliva of sheep.

The origin of the immunoglobulins in the upper respiratory tract secretion of sheep was determined by measuring the distribution between plasma and secretion of radiolabelled purified immunoglobulins and albumin. By calculation of the ratio of specific activity for each immunoglobulin between plasma and secretion, it was estimated that about 81% of IgA in secretion was of local origin, whereas IgM, IgG1, IgG2 and albumin were wholly derived from plasma. Estimates of the selectivity of transport of IgA and IgM into both respiratory tract secretion and saliva were obtained by calculation of a selective index relative to IgG1 or IgG2, which do not bind secretory component (SC). This was based on radioactivity ratios after the simultaneous injection of immunoglobulin labelled with different isotopes (IgA or IgM injected with either IgG1 or IgG2). These calculations revealed that both IgA and IgM were selectively transported into respiratory tract secretion and saliva. This provides further support for the proposition that SC-binding immunoglobulins may be transported from serum into secretions at a variety of mucosal sites dependent on SC availability. Since the IgA in serum of sheep is predominantly of gut origin, this provides an opportunity, in addition to relocation of gut-derived plasma cell precursors, by which the gut may contribute to extraintestinal mucosal responses.     

Development and persistence of West Nile virus-specific immunoglobulin M (IgM), IgA, and IgG in viremic blood donors

West Nile Virus (WNV) antibody development and persistence were investigated in blood donors who made WNV RNA-positive (viremic) donations in 2003. Plasma samples from the index donations and follow-up serum or plasma samples were tested for WNV immunoglobulin M (IgM), IgA, and IgG by using enzyme-linked immunosorbent assays. Antibody development was investigated with 154 samples collected from 84 donors 1 to 21 days after their RNA-positive, antibody-negative, index donation. WNV IgM and IgA were first detected on day 3, and all samples collected after day 9 were WNV IgM and IgA positive; WNV IgG was first detected on day 4, and all samples collected after day 16 were positive. Antibody persistence in this donor group (index donations antibody negative) was evaluated by using 128 samples collected from 89 donors on days 22 to 440 of follow-up; 88% of samples were WNV IgM positive, 86% were WNV IgA positive, and 100% were WNV IgG positive. In linear regression analysis, trendlines for WNV IgM and IgA reached the value discriminating positive from negative results at 218 days and 232 days of follow-up, respectively. Similar WNV IgM and IgA persistence trends characterized 27 donors whose index samples were positive for WNV IgM and IgA, as well as 14 donors whose index samples were positive for WNV IgG but negative for WNV IgM. These findings show that WNV IgG emerges after WNV IgM and IgA and that both WNV IgM and IgA typically persist for at least 6 months after infection. Thus, unlike some other flavivirus infections, WNV infection is not characterized by a relatively rapid disappearance of virus-specific IgA.     

The diagnostic value of serological studies in pediatric patients with acute Mycoplasma pneumoniae infection

BackgroundMycoplasma pneumoniae is a common pathogen of respiratory tract infections in pediatric patients. Serological studies are traditional methods for the diagnosis. However, early diagnosis of M. pneumoniae infections remains problematic. We investigate the value of early serum immunoglobulin A (IgA), in addition to immunoglobulin G (IgG), and immunoglobulin M (IgM) levels, in children infected with M. pneumoniae.MethodsFrom August 2016 to February 2017, we enrolled pediatric patients based on both clinical symptoms and chest x-ray, and confirmed by positive throat culture for M. pneumoniae. Serum titers of M. pneumoniae IgM, IgG, and IgA during the acute phase were checked. All respiratory samples were further analyzed by polymerase chain reaction (PCR). Diagnostic values of different tests were evaluated.ResultsFifty-six patients fulfilled the diagnostic criteria, with a median age of 4.84 years. Most of them (89.3%) were enrolled within 7 days of disease onset. PCR was positive in 71.4% of the study population. Early IgG samples were of limited value in diagnosing M. pneumoniae infection, of which 89.3% showed a negative result. Positive rates of early serum IgA and IgM were 48.2% and 46.4%, respectively. In combination with IgA and/or IgM, the sensitivity increased to 71.4% during their early clinical course.ConclusionsIn the pediatric population, combined serological tests of M. pneumoniae IgA and IgM, offer an accurate method of early diagnosis comparable to that of PCR, and can be an alternative choice for prompt detection of mycoplasma infections when PCR and culture are not available.     

Immunologic diagnosis of the cerebrospinal fluid and serum in developing brain cysticercosis

ELISA detection of specific antibodies in the serum (IgG) and cerebrospinal fluid (IgG, IgM and IgA) was evaluated in 28 patients. Diagnosis of cerebral cysticercosis and evaluation of disease activity was based on CT scan findings. Specific IgG antibodies were found in the serum in 83.3% of patients with active disease and 10% of those with inactive disease. Cerebrospinal fluid tests evidenced specific antibodies in all patients with active disease and none of the patients with inactive disease. The specific CSF antibodies were IgG (94.4%), IgM (66.6%) or IgA (66.6%). Antibody titers were significantly higher in patients with an intraventricular vesicle or cyst.     

Immunoglobulin G, A, and M--clonal restriction in multiple sclerosis cerebrospinal fluid and serum--analysis by two-dimensional electrophoresis

Immunoglobulin G, A, and M (IgG, IgA, and IgM) were purified from multiple sclerosis (MS) cerebrospinal fluid (CSF) and sera and analyzed by two-dimensional electrophoresis. The light (L)-chains of MS CSF IgG were of limited diversity and dominated by about 30 major spots and many less intense spots. CSF IgG of patients with subacute sclerosing panencephalitis (SSPE) was dominated by 10 to 20 intense L-chain spots. L-chains from patients with fungal, syphilitic, and tuberculous infections of the central nervous system (CNS) ranged from 70 to in excess of 300 spots. The patterns of L-chains in MS CSF and autologous sera were different, indicating amplified synthesis of particular L-chains in MS CNS. Cathodic IgG fractions differing in isoelectric point by 0.1 to 0.3 pH units were isolated. SSPE CSF IgG fractions were dominated by a few L-chain spots, MS CSF fractions contained less than 20 spots, and MS serum fractions contained about 200 spots. MS CSF mu-chains were similar in isoelectric point range to serum but fractionated into discrete spots compared with a diffuse pattern in serum. MS CSF IgA alpha-chain spot overlapped in mobility with serum alpha-chains except a portion of the alpha-chain complex in CSF was shifted cathodically forming discrete spots. The CSF L-chains of both IgM and IgA were completely dissimilar to serum. These studies indicate major limited diversity and compartmentalized CNS synthesis of IgG, IgA, and IgM in MS. The restricted clonal pattern is proposed as consequent to B-cell stimulation by disease-related antigen(s) with limited epitope complexity. The dominance of a small number of L-chains supports results from idiotypic analysis suggesting finite clonal complexity of MS CSF IgG and indicates the feasibility of structural analysis of MS CSF L-chains, particularly amino acid sequence determinations.     

Expression of CXCL2 in the Serum and Cerebrospinal Fluid of Patients with HIV and Syphilis or Neurosyphilis

The potential mechanisms for blood–brain barrier damage and the diagnosis of neurosyphilis in HIV patients co-infected with syphilis (HIV-S) are unclear. The aim of the study was to determine the expression of CXCL2 in the serum and cerebrospinal fluid (CSF) of HIV-S patients. A total of 34 HIV patients and 7 controls were enrolled in a HIV clinical cohort for diagnosis of neurosyphilis in Taiwan. Serum and CSF concentrations of CXCL2 were determined by ELISA. Neurosyphilis was defined as a CSF white blood cell count of ≧20 cells/μl or a reactive CSF Venereal Disease Research Laboratory (VDRL). Demographics and medical histories were collected. All the patients with HIV-S were males. Most (80 %) had sex with men (MSM) and serum rapid plasma reagin (RPR) titers of ≧1:32. The medium age was 37 (range 21–68)?years. The medium CD4 T cell counts at the time of the diagnosis of syphilis were 299 (range 92–434)?cells/μl. Eight patients (24 %) had neurosyphilis based on a reactive CSF VDRL test (n?=?5) or increased CSF white blood cell counts of ≧20 cells/μl (n?=?3). The concentrations of CSF CXCL2 were significantly higher in patients with HIV and neurosyphilis as compared to HIV with syphilis, HIV, and controls (p?=?0.012). There were no significant differences in serum concentrations between the four groups. There was a correlation between CSF CXCL2 concentrations with neurosyphilis (p?=?0.017), CSF white blood cell count (p?=?0.001), and CSF protein levels (p?=?0.005). The CSF level of CXCL2 can be used to distinguish those with or without neurosyphilis in HIV infected patients.     

ELISA versus routine tests in the diagnosis of patients with systemic and neurobrucellosis

Sera from patients in different stages of brucellosis as well as sera and cerebrospinal fluid (CSF) from patients with central nervous system (CNS) brucellosis and controls, were tested by ELISA for Brucella-specific IgG, IgM and IgA. The results were compared with culture findings, micro-agglutination (MA), slide agglutination with Rose Bengal (RB), and Brucella melitensis stained antigens (SA). In sera of patients with acute brucellosis (296), ELISA was positive for IgM (100%), IgG (97%) and IgA (98%), and comparable results were found in sera of patients with subacute brucellosis (44): IgG (100%), IgM (86%) and IgA (100%). However, in patients with chronic brucellosis (40), IgG and IgA were consistently positive (100%) while IgM was only positive in 33% of their sera. The MA and RB showed similar results, being more positive in patients with acute (98%) and subacute (84%) than in chronic (61%) brucellosis. The SA and culture showed significantly lower positive results. In the CSF of patients with CNS brucellosis (45), ELISA was positive in 100%, 20% and 85% for IgG, IgM and IgA, respectively, compared to 13% positive by culture, 25% by MA and 22% by RB. ELISA was negative in the CSF specimens from patients with brucellosis without CNS involvement (66), or meningitis other than Brucella (62), and no meningitis (144). Thus, ELISA with its IgG, IgM and IgA profiles is the test of choice in the diagnosis of patients with brucellosis, especially those with chronic or CNS infection.     

癫痫患者血液和脑脊液免疫异常在其发病机制中的作用

对７２例癫痫患者血液中的ＩｇＧ，ＩｇＡ，ＩｇＭ，Ｃ３，ＣＩＣ，白蛋白，ＣＤ４＾＋细胞，ＣＤ８＾＋细胞和脑脊液中的ＩｇＧ进行检测，并计算ＣＤ４＾＋／ＣＤ８＾＋比值，ＣＳＦ－ＩｇＧ／Ｓ－ＩｇＧ比率，ＣＳＦ－ＡＬＢ／Ｓ－ＡＬＢ比率和ＩｇＧ指数。结果表明癫痫组血液中的５项参数对比照组低，尤其是原发性和末治疗亚组。而ＣＳＦ呈现病理性的免疫增强反应，表现为原发性亚组ＩｇＧ合成，而继发性亚组患者存在血脑屏障功能     

Monoclonal antibody-based capture enzyme immunoassays for specific serum immunoglobulin G (IgG), IgA, and IgM antibodies to respiratory syncytial virus

Monoclonal antibodies (MAbs) to the fusion protein (F), attachment protein (G), and nucleoprotein (N) of respiratory syncytial (RS) virus were evaluated for use as detector antibodies in immunoglobulin G (IgG), IgA, and IgM capture enzyme immunoassays. MAb assays were tested against assays using polyclonal antibodies (PAbs) with serum specimens from patients with and without evidence of recent RS virus infection. Assays developed with N MAbs were comparable to or better than PAb assays for detecting specific IgG and IgM antibodies but were somewhat less sensitive for IgA. F MAb assays were less sensitive for IgG and IgM antibodies but identified specific IgA in some specimens negative by N MAb assay. G MAb assays were insensitive for IgG and IgM antibodies but did detect about 50% of the IgA antibodies identified by the PAb assay. The basis for the low sensitivity of the G MAb assays is unclear, since many of these specimens were positive for IgG antibodies to G by Western immunoblot. The sensitivity of MAb assays varied with patient age: N MAb assays detected specific antibody responses to RS virus in all immunoglobulin classes in both adults and infants less than 1 year of age, F MAb assays detected specific IgG responses in adults and IgA responses in both adults and infants, and G MAb assays only detected IgA responses in adults. A mixture of N and F MAbs was complementary overall, identifying 54 of 55 (IgG), 51 of 52 (IgA), and 16 of 17 (IgM) serum specimens positive by PAb assay. These MAb assays were also specific with specimens tested from persons without a history of recent RS virus infection. The availability of these MAb-based assays offers other laboratories the opportunity to have long-term, standardized reagents and tests for serological diagnosis of RS virus infection.     

Specific absorption of human serum albumin, immunoglobulin A, and immunoglobulin G with selected strains of group A and G streptococci.

Five gram-positive bacterial strains were selected for absorption studies of human serum samples. Strain AR1 (group A, M-type 1) and G148 (group G), with strong immunoglobulin G (IgG) binding capacities, and strain AW43 (group A, M-type 60), binding both IgA1 and IgA2, were compared with Staphylococcus aureus Cowan I and with Staphylococcus epidermidis L603. Both AR1 and G148 were capable of completely absorbing out serum IgG. In contrast, S. aureus Cowan I left a fraction unabsorbed, as expected from its known lack of IgG3 binding. Strain AW43 absorbed out all serum IgA, using a 10-microliter bacterial pellet for 20 microliter of serum. Serum IgM levels were slightly reduced by S. aureus Cowan I absorption. On the basis of the experiments, a bacterial mixture was designed consisting of S. aureus Cowan I and group A streptococcus strains AR1 and AW43, with absorption characteristics suitable for use in discriminating between early IgM and late IgG and IgA immune responses in routine serological work. A new type of bacteria-mammalian protein binding was discovered. Human serum albumin was completely absorbed out by strain G148 and to a lesser extent by strain AR1 and AW43. S. aureus Cowan I and S. epidermidis were negative. The binding capacity of G148 for albumin equalled that of Cowan I for IgG. The binding pattern of albumin to the strains was different from those of IgG, IgA, IgM, fibrinogen, haptoglobin, or aggregated beta 2-microglobulin and therefore seems to represent another type of bacterial-mammalian interaction with a specific albumin receptor on the surface of streptococci.     

The role of mesangial complement in the hematuria of experimental IgA nephropathy

We sought to determine if codeposits of IgG and IgM and glomerular complement, observed in most cases of human IgA nephropathy, might be important for inducing hematuria. All combinations of three binary variables, the protein immunogen, the duration of oral immunization, and the protein used for intravenous challenge, were accommodated by eight groups of BALB/c mice in an active model of IgA nephropathy. Mice drank 0.1% solutions of either of two proteins for either 6 or 14 weeks, and then were challenged intravenously with either the same protein or the alternate protein. After 6 weeks, all mice had significant increases of serum IgA, IgG, and IgM antibody to the oral immunogen. At 14 weeks, IgG and IgM antibodies were reduced, presumably due to the onset of oral tolerance, but IgA titers persisted. Nearly all mice had mesangial deposits of IgA and oral immunogen. However, only mice immunized for 6 weeks and challenged with the same protein had significant IgG and IgM deposits (100%), C3 deposits (76%), and significant microhematuria. To distinguish between the role of IgG/IgM codeposits and C3 in the pathogenesis of the hematuria, we induced passive IgA nephropathy with immune complexes of monoclonal IgA anti-dinitrophenyl antibody, dinitrophenyl-bovine albumin as antigen, and one of two monoclonal IgG antibodies specific for dinitrophenyl; one of the IgGs fixes complement, the other does not. Despite comparable mesangial deposits of IgA, IgG, and antigen, only mice given immune complexes containing the complement-fixing IgG had glomerular C3 and hematuria. Furthermore, when mice depleted of serum complement via cobra venom factor were given immune complexes containing the complement-fixing IgG, no glomerular complement was observed and no hematuria ensued. We conclude that IgG/IgM codeposits in murine IgA nephropathy do not directly cause hematuria but do induce the deposition of complement, which is in turn required for glomerular injury.     

Testing for antiphospholipid antibody (aPL) specificities in retrospective "normal" cerebral spinal fluid (CSF)

Antiphospholipid antibodies (aPL) have been found in the blood of patients with systemic and neurological disease. The rare reports of aPL in cerebral spinal fluid (CSF) have been limited mostly to IgG and IgM anticardiolipin (aCL). Our published finding of IgA aPE in the CSF of a young stroke victim prompted us to establish "normal" CSF aPL values for a panel of aPL, which included aCL, antiphosphatidylserine (aPS), antiphosphatidylethanolamine (aPE) and antiphosphatidylcholine (aPC). CSF samples were tested by ELISA for IgG, IgM and IgA aPL. In addition, the CSF samples were tested for activity in the presence and absence of phospholipid (PL) binding plasma-proteins. A total of 24 data points were obtained for each CSF sample. We tested 59 CSF samples obtained from 59 patients who were undergoing evaluation for systemic or neurologic diseases. All CSF samples had normal protein, glucose and cell counts. Ten of the 59 CSF samples (17%) had elevated aPL optical density (OD) values an order of magnitude higher than the other 49 CSF samples for one or more aPL specificity and/or isotype. One CSF sample had both PL-binding protein dependent and independent IgG aPE activity. Another CSF sample showed both IgG aPE and aPC reactivity. The remaining eight CSF samples showed single aPL findings; IgG aPE (5), IgG aPC (1), IgG aCL (1) and IgM aPC (1). Seven of 10 patients with elevated CSF values were females. As expected, most "normal" aPL OD values were substantially lower in CSF than those we have reported in blood samples from volunteer blood donors.     

Cells producing antibody to measles and herpes simplex virus in cerebrospinal fluid and blood of patients with multiple sclerosis and controls.

The B cell response against measles and herpes simplex virus (HSV) was evaluated in cerebrospinal fluid (CSF) and peripheral blood from patients with multiple sclerosis (MS) and controls by enumeration of cells secreting anti-measles and anti-HSV antibodies of IgG, IgA and IgM isotypes. We used a nitrocellulose immunospot assay which enables parallel enumeration of numbers of cells secreting total IgG, IgA and IgM. Anti-measles IgG antibody-secreting cells were present in CSF from 21 of 24 MS patients (mean 24 cells/10(4) mononuclear cells), and against HSV in CSF from seven of eight patients (mean 23/10(4) cells). No antibody-secreting cells were detectable in the patients' blood. Ten MS patients examined were negative for cells in CSF and blood producing anti-measles antibodies of IgA and IgM isotypes. Anti-measles IgG antibody secreting cells were also found in CSF from four of 18 controls, and anti-HSV IgG antibody-secreting cells in six of 13, especially in patients with subacute or chronic inflammatory nervous system diseases. Our results confirm that viral antibodies in MS are produced within CSF and that this B cell response is preferentially sequestered to this compartment. Whether this viral B cell response in MS reflects specific activation due to persistence of viral antigens or an epiphenomenon remains to be clarified.