Nuclear magnetic resonance immunoassay of tetanus antibodies based on the displacement of magnetic nanoparticles.

A nuclear magnetic resonance (NMR) immunoassay based on the application of carbon-coated iron nanoparticles conjugated with recognition molecules was designed. The principle of the assay is that ELISA plates are coated with a capture element, and then an analyte is added and detected by conjugating the magnetic nanoparticles with recognition molecules. Afterwards, the elution solution (0.1-M sodium hydroxide) is added to displace the magnetic nanoparticles from the well surfaces into the solution. The detached magnetic nanoparticles reduce transverse relaxation time (T2) values of protons from the surrounding solution. A portable NMR relaxometer is used to measure the T2. Magnetic nanoparticles conjugated with streptavidin, monoclonal antibodies, and protein G were applied for the detection of biotinylated albumin, prostate-specific antigen, and IgG specific to tetanus toxoid (TT). The limit of detection of anti-TT IgG was 0.08-0.12 mIU/mL. The reproducibility of the assay was within the acceptable range (CV < 7.4%). The key novelty of the immunoassay is that the displacement of the nanoparticles from the solid support by the elution solution allows the advantages of the solid phase assay to be combined with the sensitive detection of the T2 changes in a volume of liquid.

Evaluating the effects between metal mixtures and serum vaccine antibody concentrations in children: a prospective birth cohort study.

BACKGROUND: Many populations are exposed to arsenic, lead, and manganese. These metals influence immune function. We evaluated the association between exposure to single and multiple metals, including arsenic, lead, and manganese, to humoral immunity as measured by antibody concentrations to diphtheria and tetanus toxoid among vaccinated Bangladeshi children. Additionally, we examined if this association was potentially mediated by nutritional status. METHODS: Antibody concentrations to diphtheria and tetanus were measured in children's serum at age 5 (n = 502). Household drinking water was sampled to quantify arsenic (W-As) and manganese (W-Mn), whereas lead was measured in blood (B-Pb). Exposure samples were taken during pregnancy, toddlerhood, and early childhood. Multiple linear regression models (MLRs) with single or combined metal predictors were used to determine the association with antibody outcomes. MLR results were transformed to units of percent change in outcome per doubling of exposure to improve interpretability. Structural equation models (SEMs) were used to further assess exposure to metal mixtures. SEMs regressed a latent exposure variable (Metals), informed by all measured metal variables (W-As, W-Mn, and B-Pb), on a latent outcome variable (Antibody), informed by measured antibody variables (diphtheria and tetanus). Weight-for-age z-score (WFA) at age 5 was evaluated as a mediator. RESULTS: Diphtheria antibody was negatively associated with W-As during pregnancy in MLR, but associations were attenuated after adjusting for W-Mn and B-Pb (- 2.9% change in diphtheria antibody per doubling in W-As, 95% confidence interval [CI]: - 7%, 1.5%). Conversely, pregnancy levels of B-Pb were positively associated with tetanus antibody, even after adjusting for W-As and W-Mn (13.3%, 95% CI: 1.7%, 26.3%). Overall, null associations were observed between W-Mn and antibody outcomes. Analysis by SEMs showed that the latent Metals mixture was significantly associated with the latent Antibody outcome (ß = - 0.16, 95% CI: - 0.26, - 0.05), but the Metals variable was characterized by positive and negative loadings of W-As and B-Pb, respectively. Sex-stratified MLR and SEM analyses showed W-As and B-Pb associations were exclusive to females. Mediation by WFA was null, indicating Metals only had direct effects on Antibody. CONCLUSIONS: We observed significant modulation of vaccine antibody concentrations among children with pregnancy and early life exposures to drinking water arsenic and blood lead. We found distinct differences by child sex, as only females were susceptible to metal-related modulations in antibody levels. Weight-for-age, a nutritional status proxy, did not mediate the association between the metal mixture and vaccine antibody.

Tetanus vaccination, antibody persistence and decennial booster: a serosurvey of university students and at-risk workers.

The aim of the present research is to verify the immune status against tetanus in students and workers exposed to risk and to ascertain whether a decennial booster is necessary. Antibodies against tetanus were measured in 1433 workers and students of Padua University (Italy). The enrolment criterion was the ability to provide a booklet of vaccinations released by a public health office. The influence of age, gender, the number of vaccine doses, and the interval since the last dose was determined. Ten years after the last dose, the majority of subjects (95·0%) displayed an antibody titre above the protective level (⩾0·10 IU/ml), and half of these (49·1%) had a long-term protective level (⩾1·0 IU/ml). According to our data, titre depends on both the number of vaccine doses and the interval since the last dose (P < 0·0001). Five vaccine doses and an interval of at least 10 years since the last dose are predictive of a long-term protective titre in absence of a booster (1·97 IU/ml). These data suggest that when primary series are completed, a decennial booster is unnecessary for up to 20 years. Furthermore, we recommend measuring the antibody level before a new booster is given to prevent problems related to over-immunisation.

An Advance in Prescription Opioid Vaccines: Overdose Mortality Reduction and Extraordinary Alteration of Drug Half-Life.

Prescription opioids (POs) such as oxycodone and hydrocodone are highly effective medications for pain management, yet they also present a substantial risk for abuse and addiction. The consumption of POs has been escalating worldwide, resulting in tens of thousands of deaths due to overdose each year. Pharmacokinetic strategies based upon vaccination present an attractive avenue to suppress PO abuse. Herein, the preparation of two active PO vaccines is described that were found to elicit high-affinity antiopioid antibodies through a structurally congruent drug-hapten design. Administration of these vaccines resulted in a significant blockade of opioid analgesic activity, along with an unprecedented increase in drug serum half-life and protection against lethal overdose.

Morbidity and nutrition status of rural drug-naïve Kenyan women living with HIV.

This paper describes morbidity in a group of HIV-positive drug-naïve rural women in western Kenya. A total of 226 drug-naïve HIV-positive women were evaluated for baseline morbidity, immune function, and anthropometry before a food-based nutrition intervention. Kenyan nurses visited women in their homes and conducted semi-structured interviews regarding symptoms and physical signs experienced at the time of the visit and during the previous week and physical inspection. Blood and urine samples were examined for determination of immune function (CD4, CD8, and total lymphocyte counts), anaemia, malaria, and pregnancy status. Intradermal skin testing with tuberculin (PPD), candida, and tetanus toxoid antigens was also performed to evaluate cell-mediated immunity. Anthropometry was measured, and body mass index (BMI) was calculated. Seventy-six per cent of the women reported being sick on the day of the interview or within the previous week. Illnesses considered serious were reported by 13.7% of women. The most frequent morbidity episodes reported were upper respiratory tract infections (13.3%), suspected malaria (5.85%), skeletal pain (4.87%), and stomach pain (4.42%). The most common morbidity signs on physical inspection were respiratory symptoms, most commonly rhinorrhea and coughing. Confirmed malaria and severe diarrhea were significantly associated with a higher BMI.

Low specificity of 2 tetanus rapid tests in Cambodia.

OBJECTIVES: Rapid testing for tetanus on serum or blood allows for an immediate evaluation of individual protection against tetanus in developed countries, using a "single step" immunochromatographic technique using tetanus toxoid. The specificity of these tests, compared to the reference method for tetanus, mouse serum neutralization testing, has however never been assessed in these countries, due to the difficulty to perform serum neutralization titration in mice, because of animal testing bioethical regulations. POPULATION AND METHODS: A collection of sera from adult volunteers in Cambodia, living in rural environment, was tested for tetanus antibodies by ELISA in France, and by mouse serum neutralization in Vietnam. This allowed estimating the sensitivity and specificity of 2 rapid tetanus tests, available on the market: TQS™ and Tetanotop™. RESULTS: The sensitivity of these tests was adequate, compared to mice serum neutralization test, for a test threshold of 0.01 IU/mL, (100% for TQS™, 91% for Tetanotop™), but their specificity was very low (1% for TQS™ and 13% for Tetanotop™). CONCLUSION: The results prove that these rapid tests for the assessment of individual protection against tetanus should not be used in the adult rural Cambodian population.

Seroprotection against tetanus in patients attending an emergency department in Belgium and evaluation of a bedside immunotest.

BACKGROUND: In most emergency departments, tetanus prophylaxis currently relies on vaccination history. Bedside evaluation of tetanus immunity may improve this process. OBJECTIVES: (i) To determine the seroprevalence of tetanus immunity; (ii) to evaluate the accuracy of vaccination history in assessing tetanus immunity; (iii) to identify factors predictive of seroprotection and incorrect history. METHOD: In a prospective observational study, tetanus immunity was assessed in 784 adults using Tétanos Quick Stick (TQS). A questionnaire was completed to obtain vaccination and general histories. Immunity assessed by TQS and by vaccination history were compared with anti-tetanus antibody levels measured by the enzyme-linked immunosorbent assay (seroprotection threshold >0.15 IU/ml). RESULTS: Overall, 64.2% of patients were protected according to TQS results. Four independent predictors of seroprotection were identified: young age, birthplace in Belgium, male sex and occupational medicine consultation. TQS performance was good: kappa=0.71, sensitivity 85.3%, specificity 87.2%, positive predictive value 92.1% and negative predictive value 77.2%. Seven hundred and sixty-two participants responded to the vaccination history: 23.4% said they were protected, 22.1% that they were not and 54.5% did not know. History performance was poor: kappa=0.27, sensitivity 60.3%, specificity 73.3%, positive predictive value 81.8% and negative predictive value 45.8%. Compared with history, TQS offered a significantly better sensitivity, negative and positive predictive values, but specificity was similar. No predictor of an incorrect history was identified. CONCLUSION: Lack of protective immunity against tetanus is frequent but poorly evaluated by history taking. Several demographic characteristics are good predictors of seroprotection. TQS could be a valuable tool in selected patients to improve tetanus prophylaxis in the emergency department.

Nasal immunization studies using liposomes loaded with tetanus toxoid and CpG-ODN.

To increase the systemic and mucosal immune responses against the nasally administered tetanus toxoid, liposomes as a drug delivery system and CpG-ODN as an adjuvant were evaluated. Rabbits were nasally immunized with entrapped tetanus toxoid (TT) and CpG-ODN in neutral liposomes and systemic and mucosal immune responses were determined. Liposomes containing TT and CpG-ODN were prepared by dehydration-rehydration method. The volume mean diameter of liposomes was 2.3+/-0.6 microm. Encapsulation efficiency of TT and CpG-ODN was determined as 54.0+/-8.8 and 60.1+/-7.4, respectively. The leakage of the encapsulated TT from liposomes reached 7.38% after 3 months. Encapsulated TT kept its intact structure, and its immunoreactivity was also completely preserved, as shown by SDS-PAGE and ELISA methods. The highest serum IgG and antitoxin titers were observed in groups immunized with solution formulations (P < 0.001). However the highest mucosal sIgA titers were achieved by liposomes encapsulated with TT. CpG-ODN as an adjuvant was able to increase the serum IgG and antitoxin titers when co-administered with TT solution (P < 0.05) or co-encapsulated with TT in liposomes (P < 0.01), but failed to increase the sIgA titers in nasal lavages. No hemolysis occurred on incubation of liposomes and human RBCs. Also after nasal administration of plain liposomes to human volunteers, no local irritation was seen. Intranasal administration of liposomes encapsulated with vaccines showed to be an effective way for inducing the mucosal immune responses.

Diagnosis of tetanus immunization status: multicenter assessment of a rapid biological test.

Diagnosis of tetanus immunization status by medical interview of patients with wounds is poor. Many protected patients receive unnecessary vaccine or immunoglobulin, and unprotected patients may receive nothing. The aim of this study is to evaluate the feasibility and accuracy of the Tetanos Quick Stick (TQS) rapid finger prick stick test in the emergency department for determining immunization status. We designed a prospective multicenter study for blinded comparison of TQS with an enzyme-linked immunosorbent assay (ELISA). Adults referred for open wounds in 37 French hospital emergency departments had the TQS after receiving standard care (emergency-TQS). TQS was also performed in the hospital laboratory on total blood (blood/lab-TQS) and serum (serum/lab-TQS). ELISA was performed with the same blood sample at a central laboratory. We assessed concordance between emergency-TQS and blood/lab-TQS by the kappa test and the diagnostic accuracy (likelihood ratios) of medical interview, emergency-TQS, and lab-TQS. ELISA was positive in 94.6% of the 988 patients included. Concordance between blood/emergency-TQS and blood/lab-TQS results was moderate (kappa=0.6), with a high proportion of inconclusive blood/emergency-TQS tests (9.8%). Likelihood ratios for immunization were 3.0 (95% confidence interval [CI], 1.8 to 5.1), 36.6 (95% CI, 5.3 to 255.3), 89.1 (95% CI, 5.6 to 1,405.0), and 92.7 (95% CI, 5.9 to 1,462.0) for medical interview, blood/emergency-TQS, blood/lab-TQS, and serum/lab-TQS, respectively. The sensitivity of the blood/emergency-TQS was 76.7%, and the specificity was 98% by reference to the ELISA. TQS use in the emergency room could make tetanus prevention more accurate if its technical feasibility were improved, and our assessment will be supplemented by a cost effectiveness study.

Locally produced anti-phosphorylcholine and anti-oxidized low-density lipoprotein antibodies in gingival crevicular fluid from aggressive periodontitis patients.

BACKGROUND: Sera from patients with periodontal attachment loss contain higher concentrations of IgG anti-phosphorylcholine (anti-PC) than sera from healthy subjects. Furthermore, a large proportion of plaque bacteria bear PC-containing surface antigens, implicating the oral flora as a source of immunogen for anti-PC. Additionally, anti-PC is cross-reactive with a variety of oral bacterial antigens and human antigens such as oxidized low-density lipoprotein (oxLDL). We hypothesized that, if the oral flora is a source of PC antigens, then we should be able to detect local anti-PC and anti-oxLDL production in gingival crevicular fluid (GCF). METHODS: To test this, we collected 66 GCF samples from 15 patients with aggressive periodontitis and examined both the GCF samples and serum samples for their content of IgG anti-PC, IgG anti-LDL, and IgG anti-oxLDL by enzyme-linked immunosorbent assay. We also determined levels of anti-tetanus toxoid (anti-TT) as a non-oral antigen control. Serum and GCF concentrations of serum albumin (HSA) were also determined for use as a dilution marker. A conservative GCF:serum antibody ratio of greater than 1.5 was considered to be evidence of local antibody production. RESULTS: For the non-oral antigen TT, only one out of 62 samples contained locally produced antibody. Eight out of 64 samples (7 from a single subject) demonstrated local production of anti-LDL. In contrast, 28 out of 66 samples demonstrated local production of anti-PC, and 47 out of 66 samples contained locally produced anti-oxLDL. It was observed that A. actinomycetemcomitans strains containing or devoid of PC could absorb anti-oxLDL from human sera. Although there was a correlation between the ratios of anti-PC and anti-oxLDL (Spearman's rho = 0.35, P = 0.0037), local production of both antibodies was found in only 17 out of 65 samples, indicating that these antibodies are not always reflective of reactivity to the same antigens. CONCLUSION: The local production of anti-PC and anti-oxLDL further implicates the oral flora as a source of antigen that may mediate immune reactions of relevance to cardiovascular and other systemic diseases.

Antibodies to tetanus toxoid in women of childbearing age in Dar es Salaam and Bagamoyo, Tanzania.

Our aim was to determine tetanus immunity in women of childbearing age (15-44 years) with histories and/or documentation of having been vaccinated with Tetanus Toxoid (TT) under the Expanded Programme on Immunization in Dar es Salaam and Bagamoyo, Tanzania. Using an ELISA technique, serum levels of TT antibody, antibody avidity and distribution of TT IgG subclass antibodies were determined in 207 apparently healthy women. A TT antibody level of 0.1 IU/ml was considered protective. 99% and 100% of women in Dar es Salaam and Bagamoyo, respectively, had a TT antibody level > or = 0.1 IU/ml. Anti-toxin binding avidity was found to be high in most of the women. In addition to TT IgG3 subclass antibody, TT IgG1 subclass antibody was the most dominant subclass type. A substantial number of women also had TT IgG2 and TT IgG4 subclass antibody responses. A better recording system on TT immunization is recommended to avoid hyper-immunization of women and to optimize the cost-effectiveness of the immunization programme.

Titres of specific antibodies to poliovirus type 3 and tetanus toxoid in saliva and serum of children with recurrent upper respiratory tract infections.

A study of antibody levels (in saliva and blood) against common vaccine antigens was performed in a population of 32 children suffering from recurrent upper respiratory tract infections (URTI). None of the patients had primary or secondary immunodeficiency syndromes or other known predisposing factors for respiratory diseases. Titres of the isotype-specific antibodies immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) against two vaccine antigens--poliovirus type 3 (P3) and tetanus toxoid (TT), a viral antigen and a bacterial antigen, respectively--were measured in unstimulated saliva and serum, both in patients and in 24 healthy children (controls), by using a standard enzyme-linked immunosorbent assay (ELISA). In addition, levels of total IgA and avidity of IgA antibodies to both P3 and TT in saliva were evaluated. No difference was found between patients and controls as to levels of total IgA, or specific IgA and IgM antibodies against both P3 and TT in saliva. Furthermore, the avidity of salivary IgA antibodies against the two antigens did not differ between the two populations. However, the average concentrations of saliva-specific IgG antibodies to both the viral and the bacterial antigen were significantly lower (p <0.01 for P3 and p <0.05 for TT, respectively) in saliva of children with recurrent URTI, whereas no difference was found in serum for any immunoglobulin isotype determined compared with healthy individuals. The results of the present study provide suggestive evidence for the existence of subtle IgG-restricted defects in antibody responses at the mucosal level, but not at the serum level, in some children with undue susceptibility to URTI.

Tetanus antibody levels among adolescent girls in developing countries.

Neonatal and maternal tetanus infections remain an important cause of death in many countries. Few studies have reported tetanus toxoid antibody levels of adolescent girls. As part of the Expanded Programme on Immunization most girls receive up to 3 injections in early childhood, and many subsequently do not receive booster vaccinations until pregnant. We determined (by ELISA) tetanus antibody seropositivity in adolescent girls from Malawi (in 1996), Nigeria (in 1993) and Pakistan (in 1996), and response to tetanus vaccination in adolescent girls from Pakistan. Geometric mean titres (GMT, IU/mL) were 0.94 in 117 Malawian, 0.32 in 154 Nigerian and 1.08 in 162 Pakistani girls. In Nigeria, 54.7% of adolescents were seronegative, of whom 26.8% had a history of unsafe abortion. In Malawi and Pakistan all girls were seropositive and in Pakistan, following a booster vaccination, titres increased 3-fold, with a lower response in older girls. The results indicated that adequate childhood immunization is likely to provide protective levels through adolescence. Booster vaccination in late childhood/early adolescence should protect the majority of women throughout their reproductive lives. This practice would reduce the risks of girls exposed to infection through unsafe abortions, and may be the best option for countries seeking to improve their vaccination schedule, especially where tetanus vaccine coverage in pregnant women is unacceptably low.

Fatal tetanus in a drug abuser with "protective" antitetanus antibodies.

Tetanus is a rare disease in the United States. From 1995-1997, the average annual incidence of tetanus was 0.15/1,000,000 population. Injecting-drug users, particularly those who use heroin, are among the highest risk population for acquiring tetanus. We present a case of an injecting-drug user who was seen in the emergency department with worsening diffuse midthoracic back pain and spasms. He subsequently developed acute respiratory failure and central nervous system hypoxic injury. Serum obtained before administration of tetanus immune globulin showed a tetanus antibody titer greater than 16 times the level considered protective. Because of limited human data on the minimum protective level of neutralizing antibody, as well as reports of tetanus among individuals with "protective" antibody titers, the diagnosis of tetanus should not be excluded solely on the basis of antitetanus titers.

Levels and avidity of antibodies to tetanus toxoid in children aged 1-15 years in Dar es Salaam and Bagamoyo, Tanzania.

A study was undertaken to determine the serological response in children (aged 1-15 years) immunized with diphtheria-pertussis-tetanus vaccine (DPT) alone or with a tetanus toxoid (TT) booster dose under the Expanded Programme on Immunization in Dar es Salaam and Bagamoyo, Tanzania. Using an ELISA technique, serum levels of anti-TT antibody, antibody avidity and anti-TT IgG subclasses were determined in 138 apparently healthy children. Our findings revealed that 94.7% and 98% of children aged 1-5 years in Dar es Salaam and Bagamoyo, respectively, had anti-TT antibody levels above that considered protective (> or = 0.1 IU/ml). Among 6-15-year-old children, 53.3% in Dar es Salaam and 55% in Bagamoyo had anti-TT antibody levels > or = 0.1 IU/ml. The avidity index of anti-TT antibodies was high in most of the younger children, 84.2% in Dar es Salaam and 92% in Bagamoyo. Significantly fewer older children in Dar es Salaam and Bagamoyo (53.3% and 50%, respectively) had high avidity index antibodies. The predominant anti-TT IgG subclasses were IgG1 and IgG3. It is concluded that the current DPT immunization schedule provides adequate tetanus immunity for children under 5. However, about half of the older children had no protection against tetanus.

Transport of proteins across the human placenta.

PROBLEM: The transport of various proteins across the human placenta was investigated by comparing maternal and fetal concentrations of tetanus antigen (TT-AG), anti-tetanus (TT)-immunoglobulin G (IgG) (following maternal vaccination), IgA, human chorionic gonadotropin (hCG), human placental lactogen (hPL), and alpha-fetoprotein (AFP) at term. METHOD OF STUDY: The concentrations of the six proteins were determined using enzyme-linked immunosorbent assay in serum of maternal venous and umbilical (fetal) vein samples obtained at delivery from uncomplicated term pregnancies (n = 16). RESULTS: The ratios (mean +/- standard deviation) of fetal (umbilical) to maternal level were 1.41 +/- 0.33 (anti-TT-IgG), 0.91 +/- 0.37 (TT-AG), 0.002 +/- 0.001 (IgA), 0.003 +/- 0.001 (hCG), and 0.008 +/- 0.004 (hPL), while the maternal:fetal concentration ratio of AFP was 0.002 +/- 0.002. IgA, hCG, hPL, and AFP showed a close correlation between maternal and fetal levels varying between r2 = 0.47 to 0.73 (P < 0.004-0.0001). Because AFP is produced by the fetus while IgA originates in the mother, the appearance of small amounts of these two proteins in the maternal or fetal compartment, respectively, suggests a slow rate of diffusion following a high concentration gradient. The detection of hCG and hPL in fetal serum is also interpreted as diffusion from the maternal into the fetal blood. Anti-TT-IgG has a significantly higher concentration in the fetal as compared with the maternal serum, which is in line with the well-documented active transfer of IgG. Fetal TT-antigen levels were similar to maternal concentrations, showing a close correlation (r2 = 0.74, P < 0.0001) between the two proteins. CONCLUSIONS: The correlation between maternal and fetal concentrations of various proteins like IgA (150,000 Da), hCG (42,000 Da), and hPL (21,000 Da) suggests passive diffusion of these macromolecules across the placenta from the maternal to the fetal side, albeit at a slow rate. A similar process is postulated for AFP (70,000 Da) diffusing in the opposite direction from the fetus to the mother. There was no significant difference between the transplacental fetomaternal gradient of IgA and hCG and the maternal-fetal gradient of AFP. In view of the substantially larger volume of circulating maternal as compared with fetal blood, a significantly higher rate of crossing of AFP as compared with the other proteins must be assumed. It is uncertain whether a difference in the rate of transplacental transfer in the two directions or an additional source of AFP production in the maternal compartment explains the high maternal level. Anti-TT-IgG concentration is significantly higher in fetal than in maternal serum suggesting active transfer from the mother to the fetus. Furthermore, there is considerable transfer of TT-AG and a close correlation of fetal:maternal ratios of anti-TT-IgG (150,000 Da) and TT-AG (150,000 Da) could be an indication for a specific transfer of the antigen antibody complex.

Urinary loss of immunoglobulin G anti-F(ab)2 and anti-DNA antibody in systemic lupus erythematosus nephritis.

The objective of this study was to determine whether the low levels of serum immunoglobulin G (IgG) anti-F(ab)2 seen in some patients with active systemic lupus erythematosus (SLE) were directly related to the deposition of antibody with this specificity in the kidney or alternatively to the urinary loss of IgG anti-F(ab)2. Serum Levels of IgG anti-F(ab)2, anti-tetanus toxoid, and anti-ds DNA antibody were measured in parallel with urinary excretion of these same 3 antibodies in 28 patients with SLE nephritis and in 28 control patients with other forms of chronic kidney disease. Low levels of both serum IgG anti-F(ab)2 or anti-tetanus antibody appeared to correlate with increased levels of urinary loss of these same antibodies in some patients with SLE and in control subjects with kidney disease. However, urinary loss could not account for low serum levels of either IgG antibody in many subjects. Quantitative 24-hour urinary losses of IgG anti-F(ab)2 and anti-DNA were much higher in patients with SLE than in control subjects with kidney disease (P < .05), whereas amounts of IgG urinary loss of anti-tetanus were similar in patients with SLE and in control subjects. In nearly 1 third of SLE nephritis patients, 13% to 53% of total excreted urinary IgG showed anti-DNA enzyme-linked-immunosorbent assay reactivity. Urinary IgG in many patients with SLE showed both anti-DNA and anti-F(ab)2 reactivity, but dual anti-DNA/F(ab)2 specificity was more pronounced in affinity-isolated serum IgG anti-DNA or anti-F(ab)2 than in excreted urinary IgG molecules. The affinity of urinary IgG for either DNA or F(ab)2 was much lower than the same antibody activities measured either in serum or in kidney biopsy eluates. When the relative affinity of anti-DNA antibody in serum, urine, and kidney biopsy eluate was measured in parallel, the highest affinity antibody was found in kidney biopsy eluates, followed by serum antibody with urine antibody affinity showing the lowest values. These findings suggest a relative concentration of the highest affinity, doubly reactive IgG anti-DNA/F(ab)2 in SLE kidney tissues during SLE nephritis and implicate this process as an important factor in ongoing tissue damage.

[Permeability of sublingual mucosa to organic molecules. Limited role of sublingual absorption in aerosol vaccinations]. / La perméabilité de la mugueuse sub-linguale aux molécules organiques. Les limites du rôle de la voie sub-linguale dans la vaccination par aérosols

131I labelled tetanus anatoxin was placed in vivo, in the sublingual area in the rat. The radioactivity appearing in blood was insignificant, even after that the disappearance rate in reference animal had been taken into account. It is concluded that immunisation with aerosols is fundamentally carried out through the respiratory tract.