Clinical experience with sperm antibody testing

Of the 724 patients examined for circulating spermagglutinating antibodies by the Kibrick spermagglutination test, 95 (13.1%) were found to be positive. Almost 20% of the 406 male patients demonstrated autoantibodies. This high incidence may be explained by the selected population studied. Of 50 males tested who demonstrated more than 10% agglutination in their semen, but otherwise were normospermic, 42% demonstrated autoantibodies. Of the 318 females examined, 14 (4.4%) demonstrated sperm-agglutinating antibodies. Of the 315 male and female patients examined for circulating sperm-immobilizing antibodies by the Isojima sperm-immobilization test, 14 (4.5%) were found to have antibodies. Of the 162 males treated, 10 (6%) were positive for antibodies by this technique, as were 4 (3%) of the 153 women tested.     

Family practice and the advancement of medical understanding. The first 50 years

BACKGROUND: Few data exist on the persistence of measles antibodies after vaccination of West African infants. Therefore we examined measles antibody titers 5 to 7 years after children in rural Senegal had received high titer Edmonston-Zagreb (EZ-HT), high titer Schwarz (SW-HT) or standard titer Schwarz (SW-STD) measles vaccines in infancy. METHODS: Children had received either high titer vaccines at 5 months of age or standard titer at 10 months of age. Finger prick blood samples were tested for measles antibody 5 to 7 years later by the hemagglutinin inhibition test. RESULTS: Persistence of antibody after high titer vaccines was poor with the result that 39 and 50% of the EZ-HT and the SW-HT groups had low titers of hemagglutinin inhibition measles antibodies (< or =125 mIU/ml). Nineteen percent of the children in the SW-STD group had low titers which is a lower prevalence than in the high titer groups [relative risk (95% confidence intervals), 0.05 (0.28 to 0.88) vs. EZ-HT; relative risk, 0.38 (0.22 to 0.66) vs. SW-HT]. Geometric mean (95% confidence interval) antibody titers in children with detectable values were 616 (435 to 871) in the EZ-HT, 1106 (616 to 1866) in the SW-HT and 1271 (871 to 1741) mIU/ml in the SW-STD groups, respectively. Multivariant regression analysis showed that mean titers were 2.00 (1.03 to 3.89) times higher for children with low prevaccination antibody titers (< or =125 mIU/ml) and 3.06 (1.90 to 4.94) times higher if blood was collected in the rainy season. INTERPRETATION: Given the rapid decline in antibody titers over a 5- to 6-year period in an area where measles vaccine coverage was high, it seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody concentrations (>125 mIU/ml) in West Africa. The role of subclinical boosting by exposure to natural measles and the possible role of malaria, which increases immunoglobulin turnover, in influencing long term antibody persistence after vaccination deserve further investigation.     

Serological response to in vitro-shed antigen(s) of Tritrichomonas foetus in cattle

We developed a serological assay for detection of (l) an erythrocyte-adhering molecule(s) shed by the bovine venereal pathogen Tritrichomonas foetus and (II) serum antibodies to this antigen(s) in exposed cattle. Sera from exposed and unexposed cattle were tested for their ability to induce complement-mediated lysis of bovine erythrocytes that had been previously incubated overnight at room temperature in pH-adjusted supernatants of T. foetus culture media. Eight of 180 serum specimens from six groups of presumably unexposed cows or heifers showed a positive (> or = 1:2) hemolytic titer (specificity = 95.6%). Thirteen of 14 females in two experimentally infected groups showed a positive hemolytic titer following infection (sensitivity = 94%). In experimentally infected heifers, there was little correlation (r2 = 0.33) between serum hemolytic titers with respect to shed antigen and titers obtained in serum enzyme-linked immunosorbent assays in which whole T. foetus served as the antigen. Serum hemolytic titers rose 3 to 4 weeks sooner than did previously described vaginal mucus immunoglobulin G1 or immunoglobulin A titers with respect to whole-cell antigen or TF1.17 subunit antigen, respectively. Among 14 chronically infected bulls, only 6 (43%) showed a positive hemolytic titer. This study is the first, to our knowledge, to show a specific serological response in the host to an in vitro-shed antigen(s) of T. foetus and suggests a useful diagnostic test for potentially exposed herds.     

Antibodies to chlamydia trachomatis in semen and relationship with parameters of male fertility

To screen for infection with Chlamydia trachomatis in semen samples from asymptomatic men in couples consulting for infertility and to determine the relationship of seminal chlamydial antibodies with clinically relevant parameters of male fertility, 197 randomly chosen patients were enrolled in a prospective study. The median duration of infertility was 4 years (range 1-18). Screening for C. trachomatis and chlamydial antibodies of the immunoglobulin (Ig) A and IgG classes were performed in ejaculates and, in parallel, endocervical material from the partners of the patients and serum samples from both partners were evaluated. A comprehensive examination of semen quality included sperm analyses, semen cultures, local antisperm antibody (ASA) testing, the determination of potential infection markers, and sperm-cervical mucus interaction testing in vitro (SCMPT) and in vivo (post-coital testing). Chlamydial IgA antibodies were found in the semen samples of 18.8% (37/197) of the patients, while chlamydial IgG antibodies were found in 8.1% (16/197) of the patients. Screening for C. trachomatis was negative in all semen and cervical specimens. Only 5.5% of men remembered a past genital infection. Chlamydia antibodies (IgA/Ig/G) in semen were significantly correlated with chlamydia IgG antibodies in serum samples (P < 0.001). No marked relationship was found between the presence of seminal chlamydial antibodies and the major parameters of sperm analysis, semen cultures, local ASA and sperm penetration testing as an indicator of functional capacity. Seminal chlamydial antibodies were not significantly associated with potential infection or inflammation markers in aliquots of the same ejaculates. However, a significant relationship of chlamydial antibodies in patients' semen with past genital infections of their female partners was found with clinical relevance for a tubal infertility factor. The results indicate that in asymptomatic patients the presence of chlamydial antibody IgA or IgG in semen is not associated with reduced semen quality, potential seminal infection markers or impaired functional capacity as important determinants of male fertility; however, seminal chlamydial antibodies suggesting a previous sexually transmitted disease are significantly related to a tubal infertility factor of female partners.     

Survey of antitrypanosome antibodies and studies of their specificity and autoimmunity

As a part of investigations to characterize trypanosome infections in Taiwan, sera collected from patients admitted to Veterans General Hospital, Taipei were tested for antitrypanosome antibodies. A Trypanosoma cruzi extract-based enzyme-linked immunosorbent assay (ELISA) was used to screen and titrate 1,297 patient sera. High antitrypanosome titers were detected in 166 (12.8%) of these sera. Retitration of random samples of the high titer (HT) sera indicated a 5.4% false positive. Thirteen donors with high antitrypanosome ELISA titers were followed up. Twelve of then remained high serum titers also showed high ELISA titers against an extract of Trypanosoma conorhini. Hemocultures conducted on freshly drawn blood specimens of the 13 subjects did not provide any evidence of trypanosome infections. Electrophoretic analyses of sera from HT and low titer (LT) patients suggested differences between serum proteins of the subjects in each of the groups. Atypical reactions were observed in immunodiffusion tests performed with HT and LT sera and trypanosome extracts, while western blot analyses revealed a complex pattern of binding by both sera. The qualitative and quantitative differences in these tests suggested interactions of T. cruzi antigens with donor antibodies against unrelated antigens and/or with autoantibodies. Subsequent analyses did not indicate any association between rheumatoid factor and the reactivities of the HT sera with the parasites. However, antinuclear antibodies were detected with an indirect fluorescent antibody test (IFAT) in 50% of the HT sera and 22% of the LT sera. No differences were found between the levels of antilaminin activity of the two groups. The IFAT employing T. cruzi epimastigotes was positive for 100% of the HT sera and 22% of the LT sera. The data indicate that the high seropositivity recognized in this study is due in part to the activities of cross-reacting antibodies and/or autoantibodies in the sample population.     

Altered platelet magnesium and plasma and urinary soluble form of intercellular adhesion molecule I (sICAM-1) concentrations in insulin dependent diabetes mellitus (IDDM) patients with microalbuminuria

To examine the association between anticardiolipin (aCL) antibodies and epilepsy, we investigated the serum titers of aCL antibodies in a total 252 systemic lupus erythematosus (SLE) patients recruited in a prospective study. Twenty-one cases with epilepsy which were not attributable to any causes other than SLE were identified after being followed-up for five years. The clinical manifestations were recorded and blood samples were tested for the presence of aCL antibodies (IgG, IgM and IgA isotypes). Among 21 patients with epilepsy, 12 (57.1%), 2 (9.5%) and 2 (9.5%), respectively, had elevated baseline serum levels of IgG, IgM and IgA aCL antibodies. There was a dose-response relationship between risk of seizure and the baseline serum level of aCL antibodies (P < 0.01). The odds ratio of developing seizure were 3.7 for those who had a high level of aCL antibodies compared with those without a detectable level of aCL antibodies as the referent. Our results indicate that epilepsy as a primary neuropsychiatric event among lupus patients is associated with a high titer of aCL antibodies.     

Clinical correlates of circulating immune complexes and antibody reactivity in squamous cell carcinoma of the head and neck. The Department of Veterans Affairs Laryngeal Cancer Study Group

PURPOSE: To evaluate the correlation between the presence and titer of host-derived antibody reactivity, circulating immune complexes, and clinical course and prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: Serum samples, obtained from untreated patients with squamous cell carcinoma of the larynx entered onto a multiinstitutional trial, were evaluated for the presence of elevated circulating immune complexes (221 patients) and host-derived antibody directed against two SCCHN cell lines (107 patients). RESULTS: Patients had significantly elevated levels of circulating immune complexes as measured by C1q binding compared with normal controls. Patients with higher levels of circulating immune complexes were less likely to respond to chemotherapy. No correlations were noted between immune complex levels and stage of disease, nodal status, site of disease, recurrence, or survival. Evaluation of native antibody titers for their relationship to clinical correlates showed no statistically significant associations. In sera subjected to immune complex dissociation, patients with moderately or poorly differentiated tumors had significantly higher antibody titers when compared with patients with well-differentiated tumors. Because marked variation in the increase of antibody titers following immune complex dissociation was noted, the ratio of immune complex-dissociated to native antibody titer was examined. Patients with a high ratio had a lower proportion of complete and partial responses to chemotherapy. CONCLUSION: Our results support the conclusion that the formation of tumor-associated immune complexes in patients with SCCHN is associated with a decreased response to chemotherapy.     

Anti-Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival

PURPOSE: Anti-Hu antibodies (HuAb) recognize antigens expressed by neurons and small-cell lung cancer (SCLC). High titers of HuAb were initially reported in serum from patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) and SCLC. Preliminary studies have indicated that some SCLC patients without PEM/SN harbor low titer of HuAb in their serum, and that the SCLC of these patients may grow more indolently. Based on these observations, we conducted a multicenter prospective study of SCLC patients without PEM/SN to determine the incidence and prognostic implications of HuAb. METHODS: Serum samples were collected at diagnosis of SCLC in 196 patients without PEM/SN. HuAb were determined by immunoblot of purified recombinant HuD antigen. RESULTS: HuAb were detected in 32 (16%) of the 196 patients. Of the 170 patients who received treatment for the tumor, 27 (16%) were HuAb positive. HuAb was associated with limited disease stage (59.3% v 38.6%; P = .047), complete response to therapy (55.6% v 19.6%; P < .001), and longer survival (14.9 v 10.2 months; P = .018). In a logistic regression analysis, HuAb status was an independent predictor of complete response induction. The probability of achieving a complete response was more than five times higher in HuAb-positive than in HuAb-negative patients (odds ratio, 5.4; 95% confidence interval, 1.71 to 16.89; P = .004). Cox multivariate analysis indicated that HuAb status was not independently associated with survival. CONCLUSION: The presence of HuAb at diagnosis of SCLC is a strong and independent predictor of complete response to treatment. This feature accounts for the association between HuAb and longer survival.     

Influence of adjuvants on the induction of autoantibodies to the thyrotropin receptor

To determine the influence of adjuvant on the induction of antibodies to thyrotropin receptor (TSHR), we immunized BALB/c mice with a extracellular domain of the TSHR (ETSHR) protein in complete Freund's adjuvant (CFA), Titer Max (TM) and Gerbu. Similarly, control groups of mice were immunized with bovine serum albumin (BSA) in each of the different adjuvants. As determined by ELISA, ETSHR given along with CFA elicited high titers of antibodies to ETSHR which were mainly restricted to the IgG1 subclass. Mice immunized with ETSHR in TM also developed high titers of anti-ETSHR antibodies but had higher levels of both IgG1 and IgG2a. However, immunization with ETSHR in Gerbu resulted in low titers of antibodies, restricted to IgG1 subclass. Immunization of mice with BSA in each of the three adjuvants induced higher antibody titers to BSA. The subclass of antibodies in mice immunized with BSA in CFA and TM were predominantly IgG1 and IgG2a with lower levels of IgG2b, whereas in Gerbu treated group, antibody to BSA was restricted to IgG1 subclass. Analysis of specificity of antibodies against ETSHR, in mice immunized with ETSHR, revealed that irrespective of the adjuvant used, the dominant reactivity was against peptide 1 (AA 22-41) with weaker reactivity against several other. peptides. The only exception was in mice immunized with ETSHR in TM which also showed significant reactivity against peptide 23 (AA 352-371). Mice immunized with the ETSHR in CFA or in TM showed elevated levels of serum TSH binding inhibitory immunoglobulins (TBII). However, mice immunized with ETSHR in Gerbu, which had lower titers of antibodies to ETSHR, showed normal TBII levels. These studies showed that adjuvant composition could influence the titer, subclass and fine specificity of antibodies to ETSHR which in turn could affect the development of TBII activity.     

Multifocal motor neuropathy. Serum IgM anti-GM1 ganglioside antibodies in most patients detected using covalent linkage of GM1 to ELISA plates

IgM anti-GM1 antibodies occur with increased frequency in the serum of patients with multifocal motor neuropathy (MMN). We tested the ability of serum IgM from patients with MMN to bind to GM1 ganglioside covalently bound to secondary amino groups on ELISA plates (Co-GM1). The Co-GM1 technique detected high titer (> 1,800), selective, serum IgM binding to GM1 ganglioside in 85% of our MMN patients (23/27), a significantly greater frequency compared with figures of 37% and 52% found using our previous testing methods. Selective IgM anti-GM1 antibodies showed disease specificity. The only other patients with selective, high-titer IgM anti-GM1 antibodies had either chronic motor neuropathy without conduction block or acute immune neuropathy in China. No patient from the amyotrophic lateral sclerosis, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré, or systemic immune disorder control groups had selective IgM anti-GM1 antibodies at titers greater than 1,800 detected using Co-GM1 ganglioside as ELISA antigen. Titers of IgM anti-GM1 antibodies in MMN (averaging 31,000 +/- 15,000) were more than fourfold higher with Co-GM1 than with previous anti-GM1 assay methods, using conventional ELISA plates with GM-1 antigen alone (7,200 +/- 4,400) or in a lipid environment (3,600 +/- 1,300). We conclude that using ELISA testing with Co-GM1 antigen, serum anti-GM1 autoantibodies are a useful marker for MMN, because they are present in 85% of MMN patients and, at titers greater than 1,800, have strong specificity for immune-mediated motor neuropathies.     

Probable antibody-mediated failure of two sequential ABO-compatible hepatic allografts in a single recipient

Two sequential ABO-compatible orthotopic liver allografts failed, despite excellent initial posttransplant function, in a patient with preformed donor-specific alloantibodies. There was no evidence of cell-mediated rejection. Retrospective crossmatching of recipient serum, obtained immediately prior to the first transplant, revealed the presence of lymphocytotoxic antibodies directed against donor class I HLA B17, at a titer of greater than 1:32,768. Similarly, lymphocytotoxic antibodies directed against the second donor's class I HLA A2 phenotype were detected on retrospective crossmatching utilizing both the three-wash Amos technique (TWA-CDC), and the anti-human immunoglobulin augmented technique (AHG-CDC), at a titer of greater than 1:32,768. Anti-class I specific alloantibodies were eluted from both failed liver grafts at titers of 1:256. The hepatic necrosis in zones 3 and 2 that were observed on histologic examination, and the profound refractory consumptive thrombocytopenia subsequent to each transplant may have been the result of antibody-mediated rejection by preformed lymphocytotoxic antibodies. Despite the liver's remarkable capacity to withstand antibody-mediated injury, primary humoral rejection following ABO compatible liver transplantation may occur if extremely high titers of performed allospecific lymphocytotoxic antibodies are present.     

The persistence of genetic homogeneity among Trypanosoma brucei rhodesiense isolates from patients in north-west Tanzania

The decrease in titer of PRV antibodies in serum was evaluated at 10, 37, 67, 109 and 173 days of age in 16 non-vaccinated pigs and 43 pigs vaccinated at 3, 67 and 80 days of age with a modified live TK/gIII gene deleted pseudorabies virus (PRV) vaccine. Serum samples were analyzed for antibodies to PRV by the serum-virus neutralization test (SN), a commercial competitive ELISA (CELISA), and the CELISA OMNIMARK PRV differential (OMD) diagnostic kit. At 10 days of age, all pigs had SN titers > or = 1:4 and were CELISA+/OMD+, indicating circulating antibodies to field strains of PRV. At 109 days, all non-vaccinated pigs had SN titers < 1:4. Forty-five percent of vaccinated pigs had SN titers > or = 1:4, 56% were CELISA positive and most were CELISA+/OMD-, indicating antibodies due to vaccination. At 24 weeks of age, all pigs had SN titers > or = 1:4 and were CELISA+/OMD+ due to exposure to field strains. Although circulating maternal antibodies interfere with the development of active immunity, vaccination at 3 days of age resulted in detectable antibodies by 67 days of age, and a limited immune response could be measured at 109 days of age.     

A microagglutination test for human Brucella canis antibodies

A microagglutination test for the detection of Brucella canis antibodies in humans is described. The use of safranin-dyed B. canis organisms as antigen gave easily interpretable settling patterns and reproducible endpoints. The finding of 18 of 1,147 sera with titers greater than or equal to 1:160 resulted in a presumed false-positive rate of 1.6%. Repeat testing of these positive sera in diluent to which 0.6 m NaCl had been added showed a decrease in titer to less than or equal to 1:40 in eight. Conversely, the increased salt concentration permitted detection of blocking antibodies in two sera which were originally thought to be negative. The test provided serologic evidence for B. canis infection in four patients with otherwise undiagnosed febrile illness. The disease is underdiagnosed due to general lack of serologic testing facilities and misconceptions concerning its prevalence.     

The autoantibody response to Ro/SSA in cutaneous lupus erythematosus

BACKGROUND AND DESIGN: Seventeen patients with subacute cutaneous lupus erythematosus (SCLE) were compared with 15 patients with discoid lupus erythematosus (DLE) to evaluate the relationship of 60- and 52-kd Ro/SSA autoantibodies to the clinical diagnosis and to evaluate assays for anti-Ro/SSA. RESULTS: All serum samples from patients with SCLE had precipitating anti-Ro/SSA antibodies in immunodiffusion, and all had high titer anti-60-kd Ro/SSA in enzyme-linked immunosorbent assay. Immunoblotting was inadequately sensitive for detecting anti-60-kd Ro/SSA. Fifteen patients with SCLE had anti-52-kd Ro/SSA (11 high titer, four low titer). Only one of the 15 patients with DLE had precipitating, high-titer anti-Ro/SSA. Nine other patients with DLE had low-titer anti-60-kd Ro/SSA, and four had low-titer anti-52-kd Ro-SSA. Low-titer anti-Ro/SSA did not confer an increased risk for photosensitivity in the DLE group. CONCLUSIONS: High-titer, precipitating antibodies to Ro/SSA are typical of SCLE and unusual in DLE. Low-titer, nonprecipitating antibodies to Ro/SSA are common in DLE and could be an indication of pathogenic factors shared with SCLE. However, low titers of anti-Ro/SSA do not confer a significant risk for SCLE skin lesions. For the purpose of clinical evaluation of skin disease, immunodiffusion assays for anti-Ro/SSA are cost-effective and informative.     

Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value

Elevated amounts of antibodies specific for acetylcholine receptors were detected in 87 percent of sera from 71 patients with myasthenia gravis but not in 175 sera from individuals without myasthenia gravis, including those with other neurologic or autoimmune diseases. Antireceptor antibodies were not directed at the acetylcholine binding site of the receptor. Presence or titer of antibody did not appear to correlate with age, sex, steroid therapy, or duration of symptoms. Myasthenia gravis patients with only ocular symptoms had lower antibody titers, while the majority of titers in myasthenia gravis patients with thymoma exceeded the median titer of the myasthenia gravis group as a whole. Assay of antireceptor antibody should prove a useful test in the diagnosis of myasthenia gravis.     

Bilateral diffuse hypoperfusion of posterior temporoparietals and occipitals in Tc-99m HMPAO brain SPECT in a patient with noncommunicating hydrocephalus

We measured class-specific antibodies to the mycobacterial hsp70 protein in 67 patients with diabetes mellitus (27 type 1 and 40 type 2) with or without vascular complications. Using ELISA, the levels of IgG and IgM antibodies in the sera of diabetic patients did not significantly differ either from those of healthy control subjects or between both types of diabetes, regardless of gender, disease duration, HbA1 level, or type of vascular complication. In patients with type 2 diabetes, the mean serum IgA levels were significantly higher than those in their matched controls [274(71) mg/dl vs 208(88) mg/dl; P < 0.01]. In this group of patients, the IgA antibody titer was significantly correlated to the serum IgA level (r = 0.334; P < 0.01). Serological autoimmunity (IgG or IgM type) to hsp70 protein is common in both the normal and the diabetic population. The increased IgA levels and anti-hsp70 IgA titers in the sera of diabetics suggest a possible role of IgA in the pathogenesis of the vascular complications of diabetes mellitus.     

Safety and immunogenicity of a respiratory syncytial virus subunit vaccine (PFP-2) in ambulatory adults over age 60

The safety and immunogenicity of purified fusion protein (PFP-2) respiratory syncytial virus (RSV) vaccine was evaluated in a randomized placebo-controlled, double-blind study of 64 healthy adults over age 60. Vaccination was well tolerated with no significant acute side-effects. Twenty-nine of 33 vaccinees (87%) showed a greater than or equal to fourfold rise in serum IgG to the F protein of RSV at 8 weeks post vaccination. Twenty of 33 vaccine recipients (61%) had a greater than or equal to fourfold rise in serum neutralizing titer to group A and/or group B RSV. Response to vaccination was inversely correlated with pre-immunization serum neutralizing titers. Active surveillance throughout the ensuring winter identified three RSV infections in the placebo group and none in the vaccine group. Thus, PFP-2 was found to be safe and immunogenic in healthy older adults.     

Reactivity of trypsin in reverse micelles: pH-effects on the W0 versus enzyme activity profiles

We have adapted the new MxA gene-induction bioassay to measure neutralizing antibodies to interferon-beta1b (IFN-beta1b, the active ingredient in Betaseron) in sera from patients treated with Betaseron. This antibody assay has been validated to quantify neutralizing titers of 1:20 and above, with a precision of +/- 0.20 in log10. We have used this MxA gene-induction antibody assay to reinvestigate serum samples from multiple sclerosis (MS) patients treated with Betaseron. The titers measured were closely comparable to those obtained in antiviral assays. Data obtained by both methods show that neutralizing antibodies may appear and subsequently disappear over time in the sera of some patients treated with Betaseron. Sera from some patients contain binding antibodies to IFN-beta1b. It was shown that binding antibody titers do not correlate quantitatively or qualitatively with neutralizing antibody titers, and indeed, a number of patients develop high levels of binding antibodies but never form measurable levels of neutralizing antibodies.     

Valproic acid in prophylactic treatment of migraine

AIM: To determine whether an oral tetravalent rotavirus vaccine (RV-TV) can be safely coadministered with a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP/Hib) and oral poliovirus vaccine (OPV) to healthy infants without interfering with the immune responses to any of the component antigens. METHODS: Two hundred sixty-seven infants ages 2 to 3 months were randomly assigned in a double blind fashion to receive three doses of either placebo or RV-TV, each containing 4 x 10(5) plaque-forming units, concurrently with DTP/ Hib (Tetramune) and OPV at approximately 2, 4 and 6 months of age. Infants were followed for 5 days after each dose for the occurrence of adverse events and subsequently until 3 to 6 weeks after the third dose of RV-TV or placebo. Immune responses were assessed by measuring the postvaccination serum antibody titers to each component of DTP/ Hib and OPV at 3 to 6 weeks after the third dose. RESULTS: The percentage of infants who attained protective antibody titers and the distribution of antibody titers against diphtheria toxoid, tetanus toxoid and H. influenzae type b were not statistically different between RV-TV and placebo recipients. The distribution of antibody titers against different antigens of Bordetella pertussis (agglutinins, pertussis toxoid, filamentous hemagglutinin, fimbriae antigens and the 69-kDa outer membrane protein) was compared and no significant differences were found. The percentage of infants with detectable neutralizing antibodies against the three serotypes of poliovirus and the distribution of antibody titers was not statistically different between RV-TV and placebo recipients. There were no clinically meaningful differences in postvaccination reactions between RV-TV and placebo recipients. CONCLUSIONS: Three doses of RV-TV can be safely coadministered with three doses of DTP/ Hib and OPV without diminishing an infant's serum antibody responses to each component of these vaccines. Therefore RV-TV can be given at the standard childhood visits at 2, 4 and 6 months of age.     

The platelet factor 3 assay and circulating immune complexes as studied on non-thrombocytopenic patients with systemic lupus erythematosus

Sera from 21 patients with systemic lupus erythematosus (SLE) were tested with a platelet factor 3 (PF3) assay. A control serum (pooled blood group AB serum) was always run in parallel with the test sera. The test and control sera were run in duplicate and for each patient the mean recalcification time was used for the calculation of the test serum: AB serum ratio. Concomitantly, the patients' serum concentrations of circulating immune complexes (CIC) were measured by using the Raji cell radioimmunoassay. 20 healthy hospital employees served as controls. In the latter subjects the mean test serum: AB serum ratio was 0.99 (range 0.92-1.09), their CIC concentrations being less than or equal to 16 micrograms/ml. 7 of the SLE patients had CIC values less than or equal to 16 micrograms/ml, and their test serum: AB serum ratios ranged 0.95-1.09. All the remaining SLE patients had elevated values for CIC. In the total material of SLE there was a highly significant (r = -0.87; P less than 0.001) negative correlation between the test serum: AB serum ratios and the values for CIC. It is widely held that the so-called PF3 immunoinjury test detects circulating antiplatelet antibodies. The present results, however, strongly suggest that the assay rather or also detects CIC which like antiplatelet antibodies may damage platelets as we and others have shown in prior publications.