Lung-reactive antibodies in sera of patients with farmer's lung disease

Lung-reactive antibodies were detected in sera of patients with farmer's lung disease and in sera of healthy persons. A solid-phase radioimmunoassay was adapted for measurement of titers of human antibodies to sodium-dodecyl-sulfate-solubilized lung proteins. The titers of antilung antibodies in patients sera were 2-5 times as much as those of healthy persons. Using the immunoblotting technique, antibodies to individual lung polypeptides could be detected. Although the specificity patterns of antibodies to lung polypeptides differed from one serum to another, patients sera contained, in general, antibodies to larger numbers of lung polypeptides as compared to sera of healthy persons. The relationship between antilung antibodies and hypersensitivity pneumonitis is discussed.     

Neutralizing antibodies against two HIV-1 strains in consecutively collected serum samples: cross neutralization and association to HIV-1 related disease.

97 sera collected during a 10-year period from 10 HIV-1 infected individuals were tested for neutralizing capacity against a virus isolate FICPH-22 obtained from a Danish AIDS patient, and the laboratory strain HTLV-IIIB. Three patterns of serum neutralizing activity were demonstrated: (a) patients developing high neutralizing activity against both HIV strains; (b) patients developing high neutralizing activity against the Danish virus isolate; and (c) patients developing only low titers of neutralizing antibodies (NA) against both HIV strains. The HTLV-IIIB strain was less sensitive to serum neutralization than the FICPH-22 isolate and the appearance of NA against HTLV-IIIB was typically lacking several years behind that against FICPH-22 indicating a broadening of the NA response over time. No difference in clinical outcome was observed comparing patients reaching high titers of NA and patients with low titers. Development of AIDS among patients reaching high titers of NA was preceded by a decline in NA titers, indicating an association of high titers of NA with the healthy carrier state and of declining or low titers of NA with disease progression. The majority of the neutralizing activity was mediated by IgG, but some neutralizing activity was demonstrated in the IgG depleted serum, indicating the presence of additional neutralizing substances in serum.     

Characterization of serum neutralization response to the human immunodeficiency virus (HIV)

To determine the clinical significance of human neutralizing antibodies to the human immunodeficiency virus (HIV), we measured serum neutralization in patients with different clinical outcomes following HIV infection. Serum neutralization titers ranged from less than 1:5 to 1:100. The neutralization response after HIV infection appeared slow, with neutralization titers remaining low, at or below 1:5, at 7 months following seroconversion. Comparison of 78 HIV seropositive subjects with AIDS, AIDS-related complex, or no symptoms failed to reveal any significant differences in titer which correlated with clinical status. However, a greater proportion of AIDS patients with Kaposi's sarcoma (11/12) had neutralization titers of 1:20 or greater than did AIDS patients with opportunistic infections (2/11). Serum samples were analyzed by Western blot for their reactivity to specific viral proteins. Clinical status could not be predicted by a particular serological profile. However, sera which reacted with the HIV major envelope glycoprotein gp120 tended to have higher neutralization titers, suggesting that gp120 may be a target of anti-HIV neutralizing antibody in man.     

Dual antibody rises to cytomegalovirus and human herpesvirus type 6: frequency of occurrence in CMV infections and evidence for genuine reactivity to both viruses

The frequency of high (greater than 256) IgG anti-human herpesvirus type 6 (HHV-6) titers in sera known to be positive for IgM anti-cytomegalovirus (CMV) or IgM anti-Epstein Barr virus (EBV) was significantly greater than in sera from healthy controls or from a group of ill patients who were CMV and EBV IgM-negative (15/25 and 17/25 vs. 1/25 and 2/25, respectively, P less than .001). There was serologic evidence of simultaneous HHV-6 infection or reactivation (a rise in IgG anti-HHV-6 titer or the presence of IgM anti-HHV-6) in sera from 14 of 17 primary CMV infections. In 5 of the 10 patients with concurrent rises in IgG titers to both viruses, the rise in IgG anti-HHV-6 preceded that of IgG anti-CMV. Complete removal of IgG anti-CMV reactivity from 5 sera from patients who had a primary CMV infection with a rise in IgG anti-HHV-6 titer had no effect on the IgG anti-HHV-6 titer of those sera, demonstrating that the rise in HHV-6 IgG titer was not a consequence of anti-CMV antibodies cross-reacting in the HHV-6 IgG assay.     

Detection of specific IgM antibodies for the diagnosis of Mycoplasma pneumoniae infections: a clinical evaluation

The diagnostic value of detection of specific IgM antibodies was analysed in Mycoplasma pneumoniae infections. In a retrospective clinical and serological study, M. pneumoniae IgM antibodies were determined by a mu-capture ELISA using enzyme-labelled antigen. The study group consisted of 91 patients with significantly raised titers in paired sera or a single high titer of complement fixation antibodies. About 40% of the patients had been treated with antibiotics ineffective against M. pneumoniae infections prior to admission to hospital. Treatment with erythromycin or tetracycline was shown to give a shorter period of fever compared to if no or ineffective therapy was given. Specific IgM antibodies were detected in about 80% of sera sampled 9 days or more after onset of symptoms. In sera sampled at 7-8 days after onset IgM antibodies were found in about 40% of the sera but only occasionally in sera sampled earlier. In the age group 0-20 years 88% of the patients developed an IgM response. In the higher ages (greater than 60 years) a significantly lower rate of IgM responders was observed.     

Secretory immunity in influenza

The dynamics of secretory antibody formation, the duration of secretory antibody preservation, and changes in the concentration of secretory antibodies to antigens other than influenza virus were studied in 64 patients with influenza A, 105 patients with influenza B, and 23 persons who had had influenza A. Severe forms of influenza A were accompanied by antibody accumulation in sera and nasal secretions; in some cases of mild forms of this infection, this process was limited by the humoral immunity system. In the first days of severe forms, transudation of antibodies from sera to nasal secretions was noted. Secretory antibodies to influenza A virus were preserved at titers of greater than or equal to 1:4 for four to eight months in persons with mild forms of the disease and for more than eight months in those with severe influenza A complicated with pneumonia. Decreases in the titer of antibodies to agents other than influenza A virus, including influenza B virus, respiratory syncytial virus, adenovirus, and staphylococcus toxin, were demonstrated in association with rises in titers of antibody to influenza A virus. Among patients with influenza B, who were infected with a new influenza virus variant, the formation of circulating antibodies was more intensely stimulated than was the formation of secretory antibodies. No correlation between the level of IgA and the antibody titer in nasal secretions was found.     

The prevalence of antibodies to Rickettsia rickettsii in an area endemic for Rocky Mountain spotted fever

A study of Rickettsia rickettsii was conducted in Rowan, Cabarrus, and Granville counties, North Carolina in an attempt to define the prevalence of endemic infection in this area. Serum samples were obtained from 1,976 healthy persons and tested by indirect hemagglutination for detectable antibodies to R. rickettsii. Of this group, 568 (28.7%) had detectable antibody (greater than or equal to 1:8), 80 (4%) had titers greater than or equal to 1:64, and 1,408 (70%) had no detectable antibody (less than or equal 1:8). Indirect immunofluorescence testing for antibody was also performed for 315 (15%) of the serum samples, of which 301 (95%) had undetectable titers and 14 (5%) had detectable titers ranging from 1:8 to greater than or equal to 1:64. Serological reactivity by indirect hemagglutination was detected in persons in the absence of known Rocky Mountain spotted fever. The study failed to show a good correlation of either the height of the geometric mean titer or percentage of seropositive persons with the previously determined age-related rates of acquisition of the disease. These data suggest that the antibodies measured may not be specific for R. rickettsii or that the antibody levels wane with time or both. It is probable that unrecognized infection occurs, but the true incidence or prevalence cannot be determined by available serological tests.     

High levels of antibodies against Clq are associated with disease activity and nephritis but not with other organ manifestations in SLE patients.

OBJECTIVE: Serum concentration of antibodies to C1q (C1qAb) has been reported to be elevated in a high percentage of patients with systemic lupus erythematosus (SLE). The associations of high C1qAb levels with different clinical manifestations and the activity of the disease, however, are not definitely understood. METHODS: We measured the levels of IgG type C1qAb in the sera of 137 patients with SLE using an ELISA method. RESULTS: Serum concentrations of C1qAb were found to be higher (p < 0.0001) in SLE patients than in healthy controls. High titer (> 66 AU/ml) C1qAb was found in 40/137 (29.2%) SLE patients, and 4/192 (2.1%) healthy controls (p < 0.0001). A strong negative correlation (R = -0.4, p < 0.0001) between the age of the patients and the C1qAb titers could be detected. C1qAb levels in clinically active SLE patients significantly (p < 0.0001) exceeded those measured in the sera of patients in the inactive stage of the disease. A significant positive correlation was detected between C1qAb levels and the laboratory activity markers (anti-DNA, low C3 level) of the disease. We found a significant negative correlation between levels of C1qAb and a negative acute phase protein, alpha2-HS-glycoprotein. Renal involvement was present in 11/40 (27.5%) and 11/97 (11%) of the patients with high and low titers of C1qAb, respectively (p = 0.038). The prevalence of other organ manifestations was, however, the same in the patients with or without high titer C1qAb. CONCLUSION: These findings indicate that C1qAb measurement is a useful method for detecting the activity of SLE and predicting renal manifestations, but not other organ involvement in the disease.     

Prevalence of antibodies to Legionnaires' disease. A seroepidemiologic survey of Michigan residents using the hemagglutination test.

The indirect fluorescent antibody test and a microhemagglutination technique detected antibodies in human sera to Legionnaires' disease antigen about equally. Since the hemagglutination technique was simpler, more rapid, and less expensive, we used it to ascertain the prevalence of antibody in 1200 sera from apparently healthy, nonhospitalized Michigan residents. Prevalence was analyzed by age, sex, geographic location (county or residence), and season of the year. There was a significant difference in prevalence between seasons: 91 of 600 sera (15.2%) from February to March 1978 had a titer equal to or greater than 1.16, contrasted with 179 of 600 sera (29.8%) from August to September 1978. This difference was independent of age and sex. There was no significant difference by geographic location, sex, or age except for decreased prevalence for persons 60 years or older.     

Frequency of antibody to hepatitis C virus in asymptomatic HBsAg-negative chronic active hepatitis.

To determine the frequency of antibodies to hepatitis C virus in asymptomatic patients with HBsAg-negative chronic active hepatitis, sera from 30 consecutive patients with few or no symptoms of liver disease were tested by an enzyme immunoassay. The reactivity of antibodies detected by enzyme immunoassay against hepatitis C virus encoded antigens was determined by recombinant immunoblot assay. Antibodies were detected in 11 of the 30 patients (37%) and eight of the seropositive sera (73%) were reactive by recombinant immunoblot assay. Nonreactive patients were weakly positive by enzyme immunoassay (sample/cutoff ratio, less than or equal to 1.9) in contrast to reactive patients (sample/cutoff ratio, greater than or equal to 6.3). The prevalence of immunoserologic markers was similar in patients with and without antibodies (78 vs. 87%) but high titers (greater than or equal to 1:160) were more common in seronegative patients (53 vs. 11%). Additionally, seronegative patients had smooth muscle antibodies (83 vs. 25%, p less than 0.05) and concurrent extrahepatic immunologic diseases (37 vs. 9%) more commonly than seropositive counterparts. We conclude that asymptomatic patients with HBsAg-negative chronic active hepatitis frequently have antibodies to hepatitis C virus. These antibodies commonly react to specific viral antigens, especially if the enzyme immunoassay is strongly positive. Seropositive patients infrequently have concurrent immunologic disorders or smooth muscle antibodies. Immunoserologic markers lack diagnostic specificity except in higher titer.     

Evaluation of serological response to Bartonella henselae by enzyme immunoassay in cat scratch disease

The IgG and IgM titers to Bartonella henselae were determined by an enzyme immunoassay (EIA). The EIA test for detection of IgG and IgM antibodies to B. henselae concerning CSD showed that 8 (40%) of 20 patients with CSD had a serum IgG antibody titer of 12 EIA unit or more and that 5 (25%) patients had a serum IgM titer of 12 EIA unit or more. Totally 12 (60%) of the 20 patients with CSD were seropositive for B. henselae. The mean age of IgG positive patients were higher than IgM positive patients. The IgM antibodies to B. henselae disappeared within 4 to 12 weeks after onset of disease. The IgG antibodies to B. henselae disappeared within 3 to 8 weeks after onset of the symptoms in 2 cases of CSD. Another 2 cases CSD produced high levels of IgG antibodies in the acute phase of the disease. Different course of IgG and IgM antibody titers were found in sera from patients.     

Effects of passive immunization in patients with the acquired immunodeficiency syndrome-related complex and acquired immunodeficiency syndrome.

Infection with the human immunodeficiency virus type 1 (HIV-1) is usually followed by a vigorous immune response that temporarily protects against disease progression. After a variable asymptomatic period, acquired immunodeficiency syndrome (AIDS)-related complex (ARC) and AIDS develop in most infected individuals. We have demonstrated that healthy HIV-1-infected individuals have neutralizing antibodies and a high titer of antiviral antibodies. In contrast, AIDS patients have undetectable levels of neutralizing antibodies, low titers of antiviral antibodies, and, frequently, HIV p24 antigenemia. These observations prompted us to attempt passive immunization in ARC and AIDS patients. Ten consistently viral-antigen-positive patients (mean, greater than 6 months) were treated, resulting in sustained clearance of p24 antigen. Patients either maintained or increased their antiviral antibody titers. The raised titers result from increased antibody synthesis by the recipients. Circulating CD4+ cell counts were unchanged after 2 months. By the third month none of these patients remained in hospital. As this treatment was of minimal toxicity, it merits wider evaluation in ARC and AIDS patients.     

Assay of specific anti-Chlamydia pneumoniae antibodies by ELISA method. 3. Setting of serological criteria]

"HITAZYME C. pneumoniae" (or "HITAZYME CPN", for short) is a diagnostic reagent that has been recently developed by adopting an ELISA method for detection of anti-Chlamydia pneumoniae (C. pneumoniae) antibodies. When this reagent is used under a current diagnostic standard that has been set as a provisional standard, however, high antibody positive rates are often produced for both IgG and IgA even using the specimens of healthy persons. So, it is difficult to distinguish C. pneumoniae-infected patients from healthy persons. Therefore, this time, we tried to establish a new diagnostic standard by setting up of special cut-off values for a single serum and rise rates of antibody titers for paired sera to improve the accuracy for diagnosis of C. pneumoniae infection. For a single serum testing, we set a special cut-off value at ID 3.00 for both IgG and IgA, so that most healthy persons fall within the range of the "negative" zone. This value was based on the calculation of "Mean+2SD" using measurement results (or IDs) of healthy persons. When this cut-off value was applied, the rate of > or = ID 3.00 for either IgG or IgA was 7.6% for healthy persons, and 64.9% for infected patients. (The rate reached 76.4% when the highest IDs of multiple specimens taken from each patient for this test were used in calculation) As a diagnostic standard for a single serum, therefore, it was defined that: "If ID is 3.00 or greater for IgG and/or IgA, it is highly likely that the case has an acute or a present infection." Using paired sera, we could confirm almost a linear relationship between the results by HITAZYME CPN and those by micro-IF method. Under micro-If method, if the antibody titer increases four times or greater using paired sera, acute infection is diagnosed. As it was found that the four-fold increase in antibody titer corresponds to the increase of 1.35 in ID for IgG and 1.00 for IgA, we defined a diagnostic standard for paired sera as follows: "If ID increases by 1.35 or greater for IgG, and/or if ID increases by 1.00 or greater for IgA, the case may be diagnosed as acute infection."     

Presence of antibodies to a putatively immunosuppressive part of human immunodeficiency virus (HIV) envelope glycoprotein gp41 is strongly associated with health among HIV-positive subjects.

The IgG response to gp41 (envelope glycoprotein of Mr 41,000) of the human immunodeficiency virus (HIV) was studied with eight synthetic peptides derived from three different regions of the protein. We tested sera from 17 HIV-seronegative and 68 HIV-seropositive subjects in an enzyme immunoassay. No HIV antibody-negative serum reacted with any of the peptides. The peptide HIV-env 583-599 has a sequence similarity with immunosuppressive peptides derived from the transmembrane proteins of other retroviruses. Antibodies to this 17-mer (HIV-env 583-599; hereafter also referred to as pHIVIS, putative HIV immunosuppressive sequence) were detected in 27 of the 35 sera from healthy HIV-positive persons but only in 1 of the 33 sera from patients with HIV-related disease. Another 17-mer, displaced four amino acids N-terminally from pHIVIS, reacted with fewer of the sera from healthy seropositive subjects than pHIVIS but with no serum from ill seropositive patients. HIV-env 586-603, which shares two-thirds of its sequence with pHIVIS, reacted with the sera from nearly all subjects, regardless of clinical status. The remaining five peptides did not discriminate between healthy and ill seropositive subjects either but gave lower reactivity rates. HIV-positive sera thus exhibited distinct patterns of reactivity with subsequences of gp41. We have mapped two overlapping epitopes within a narrow part of gp41; antibodies to the most N-terminally located of the two--i.e., the pHIVIS-reactive antibodies--might counteract a possible immunosuppressive effect of gp41.     

Antibody response in Lyme disease: evaluation of diagnostic tests

The antibody response to the Ixodes dammini spirochete was determined in 41 serial serum samples from 12 patients with Lyme disease. By enzyme-linked immunosorbent assay (ELISA), 11 of the 12 patients had higher titers of specific IgM antibody (greater than 1:200) during early disease than did 40 control subjects. Specific IgM antibody titers, which correlated with total amounts of IgM antibody (P less than .001), sometimes remained elevated throughout the illness. During neuritis, nine of 10 patients had higher specific IgG antibody titers (greater than 1:200) than did controls, and when arthritis was present, all had such titers, which remained elevated after months of remission. In the ELISA, antibody responses determined by single or serial dilutions were similar, but the ELISA was more sensitive and specific than was immunofluorescence. Adsorption of sera with Borrelia hermsii generally resulted in a fourfold decrease in titers of cross-reactive antibodies, but the titers of sera from patients with Lyme disease were also reduced. Currently, the ELISA, without adsorption, is the best diagnostic test for Lyme disease.     

Seroepidemiologic evaluation of antibodies to rotavirus as correlates of the risk of clinically significant rotavirus diarrhea in rural Bangladesh.

A case-control study was conducted among children and adult women in rural Bangladesh to evaluate whether serologic immunity to rotavirus was associated with a lower risk of rotavirus diarrhea of sufficient severity to cause patients to seek medical care. Acute-phase sera from 219 cases of rotavirus diarrhea, detected among patients treated in three diarrheal treatment centers, were compared with sera from 477 contemporaneously selected community controls. Overall, serum IgG antirotavirus antibody titers were nearly one-fourth as high in cases as in controls (107 vs. 417 units/ml; P less than .001). Among persons aged greater than or equal to 8 months, in whom titers of maternal antirotavirus antibodies should have been negligible, even the lowest range of detectable titers (100-200 units/ml) was associated with a substantial (75%, P less than .05) reduction of the risk of rotavirus diarrhea. We conclude that titers of serum IgG antirotavirus antibodies induced by earlier infection were inversely related to the risk of clinically significant rotavirus diarrhea.     

斑点免疫金银染色法诊断囊虫病的研究

用斑点免疫金银染色法(Dot-IGSS)和Dot-ELISA检测40份确诊为囊虫病患者的血清。两种方法检测的阳性率均为100％,用Dot-IGSS检测,40份血清的平均滴度为1:27470,显著高于用Dot-ELISA检测的平均滴度1:9069(P<0.01)。检测50份义务献血员血清,假阳性率分别为2％和4％。10份日本血吸虫病人血清分别有1份和2份出现假阳性。与肝吸虫病人血清无交叉反应,与包虫病人血清有明显的交叉反应。     

Antibodies to cardiac tissue in acute ischemic heart disease

Serially collected sera of 117 patients with acute ischemic heart disease were studied for the presence of antibodies to cardiac tissue by the passive hemagglutination technic. The average titer of these antibodies in 71 patients with acute myocardial infarction increased severalfold from admission to a peak after two to four weeks of hospitalization, and then declined. Sera of 46 patients with acute coronary insufficiency showed on the average a less pronounced rise and an earlier peak.

Of 50 patients with acute myocardial infarction, 23 (46%) showed a fourfold or more increase in titer during the first month, while of the 33 patients with acute coronary insufficiency, 14 (42%) showed a similar rise. Maximum titers of 80 or higher were found in 20 of the 50 patients (40%) with acute myocardial infarction and 9 of 33 patients (27%) with acute coronary insufficiency. Many patients showed low titers at all times.

Only 1 patient in the series had clinical features suggesting the postmyocardial infarction syndrome. He had high titers during the acute stage of his infarct, but no sera were obtained during the convalescent period. The postmyocardial infarction syndrome did not develop in any of the 11 patients who had titers of 80 beyond the first month.

The observation of the development of circulating antibodies to cardiac tissue in acute ischemic heart disease does not in itself permit conclusions regarding the pathogenetic significance of such antibodies.     

Racial difference in mortality among U.S. veterans with HCV/HIV coinfection

OBJECTIVES: This study was performed to examine the impact of viral coinfections and race on clinical and virological outcome of hepatitis C virus (HCV) infection. METHODS: Three groups of patients (265 HCV/HIV coinfected, 251 HCV monoinfected, 227 HIV monoinfected) were identified between 2000 and 2002 from the computerized patient record system at the Philadelphia VA Medical Center and analyzed for clinical and virological parameters. RESULTS: HCV/HIV coinfection was associated with higher frequency of liver function abnormalities (37% vs 21% vs 20%; p < 0.0003) and greater mortality (17% vs 6% vs 9% over 3 yr period, p = 0.0003, p = 0.027) compared to HCV or HIV monoinfection, respectively. However, HCV/HIV coinfection was not associated with worsened HIV-related parameters (CD4 count, HIV titer, and use of antiretroviral therapy) or increased HCV titers compared to HIV or HCV monoinfection in our population, respectively. Interestingly, mortality among HCV/HIV coinfected patients was significantly greater in white than in black patients (31% vs 15%, p = 0.011). This racial disparity in mortality was not apparent in the monoinfected groups and not explained by HBV coinfection or history of alcohol use disorder. CONCLUSIONS: We conclude that HCV/HIV coinfection is associated with worsened liver disease and higher mortality than HCV- or HIV-monoinfection without directly influencing CD4 count and HCV or HIV titers. Furthermore, we demonstrated a racial disparity in survival of HCV/HIV-coinfected patients that needs further investigation.     

Electrophoretic analysis of human herpesvirus 6 polypeptides immunoprecipitated from infected cells with human sera.

Proteins of human herpesvirus 6 (HHV-6) eliciting human antibody responses were examined in serum from healthy adults and patients with AIDS, chronic fatigue syndrome, Hodgkin's disease, and Sj?gren's syndrome. HHV-6 IgG antibody titers measured by immunofluorescence (IF) ranged from 1:10 to 1:1280. Lysates of HHV-6-infected and uninfected cells labeled with [35S]methionine, [3H]glucosamine, and 125I were immunoprecipitated with sera and analyzed electophoretically. Sera with IF titers greater than or equal to 1:20 immunoprecipitated greater than 20 [35S]methionine-labeled HHV-6 polypeptides of approximately 26-180 kDa. At least 10 HHV-6 glycoproteins and 8 HHV-6 polypeptides associated with the surfaces of infected cells were recognized by human sera. The approximate molecular masses of glycoproteins immunoprecipitated by human sera were similar to those immunoprecipitated by monoclonal antibodies. The labeling intensity of HHV-6 protein bands increased with increasing IF titer, and the effect was most prominent for HHV-6 glycopolypeptides. No reactivities with specific HHV-6 polypeptide(s) were characteristic of a given patient group. These findings suggest that HHV-6 glycoproteins are good targets for human antibody responses.