Paul Andersen

Bordetella pertussis and Chronic Cough in Adults

To evaluate Bordetella pertussis as a cause of persistent cough in adults, we examined 201 patients who had a cough for 2-12 weeks and no pulmonary disease. We obtained the following at presentation: medical history, chest radiograph, respiratory function measurement, nasopharyngeal aspirate for polymerase chain reaction (PCR), nasopharyngeal swab specimen for culture, and a blood sample (acute serum). Four weeks later a second blood sample (convalescent serum) was obtained. Control sera were obtained from 164 age-matched healthy blood donors with no history of cough during the previous 12 weeks. Four patients were B. pertussis culture-positive; 11 (including the culture-positive patients) were B. pertussis PCR-positive; and 33, including 10 of the 11 PCR-positive patients, had serological evidence of recent B. pertussis infection. Pertussis-positive and -negative patients could not be discriminated by a history of cough. We conclude that B. pertussis infection is a common cause of persistent cough in adults. This is of concern, because these patients may be B. pertussis reservoirs from which transmission may occur to infants, in whom the disease can be devastating.

Autoantibodies in untreated and treated essential hypertension. I.

Using the indirect immunofluorescence method, autoantibodies (AB) of IgG and IgM classes were investigated in sera from 161 consecutive patients with essential hypertension and compared with those from 78 healthy normotensive subjects of the same composition by age and sex, and without any family history of hypertension. The frequency of one or more AB was as high in 78 untreated (15.3%) as in 83 treated patients (13.0%) and was in the controls 9.0% (n.s.). In the treated patients, the AB were associated with heart involvement (p less than 0.02). In the untreated patients, antinuclear antibodies of IgG class were associated with BP (p less than 0.01) and fundus grading (p less than 0.005). A family history of hypertension was found in 23.5% of the hypertensive males with AB and in 9.0% of the normotensive males (p less than 0.10). These results are discussed in relation to reports of an association of AB with cardiovascular diseases. It is concluded that the presence of AB in essential hypertension is not necessarily due to drug induction.

Autoantibodies and vascular events in essential hypertension: a five-year longitudinal study.

The relationship between serum autoantibodies and vascular events was investigated in 140 patients with essential hypertension during a five-year period. The influence of time upon incidence of autoantibodies was assessed in 55 normotensive controls of roughly the same distribution of age and sex. Thirty-four patients experienced a vascular event, which was fatal in 10 cases (7.1%). Eight of these 10 patients had autoantibodies in serum before the events, and the presence of autoantibodies at entry to the study tripled the five-year relative risk for vascular events. Antinuclear antibodies (ANA) and smooth muscle antibodies (SMA) especially contributed to this increased risk. The vascular events were followed by a significantly increased occurrence of ANA. In the control subjects no events occurred and no significant increases in the presence of autoantibodies were found during the five years. ANA and SMA positive sera showed no significant complement fixing properties, and the autoantibodies studied seemed to be secondary to tissue damage. Despite this, they seemed to reflect an ongoing injury of the vascular bed.

An indirect immunofluorescence study of antibodies to Aspergillus fumigatus in sera from children and adults without aspergillosis

An indirect immunofluorescence (IF) method for detection of antibodies of Aspergillus fumigatus was developed: it used cryosections of formaldehyde-treated mycelium as antigen. Mycelial age was found to be of importance for titer determination, and growth in Czapek-Dox broth for 48 h at 37 degrees C was considered optimal. Fluorescein-conjugated rabbit antisera to human immunoglobulins reacted by direct IF with A. fumigatus but this staining could be abolished by absorption of conjugates with homogenized mycelium of A. fumigatus. Chessboard titrations revealed plateau end-points of conjugates in the range 0 . 05-0 . 2 antibody units ml -1, which is the same range as found in other systems. Sera from 54 adults and 69 children not suspected of having fungal disease were investigated for antibodies to A. fumigatus. IgG antibodies were present at birth and the prevalence and titers fell during the first half year. Through childhood the prevalence and titers of IgG and IgM as well as IgA antibodies increased towards adult levels. In adults IgG antibodies in titers of 40 to 5120 were present in all 54 subjects tested, IgM antibodies in titers 10 to 160 occurred in 91% and IgA antibodies in titers of 10 to 80 in 78%. These findings may be explained by continuous exposure through childhood and adult life to antigens of A. fumigatus or to cross-reacting antigens.

Activation of the respiratory burst by Pneumocystis carinii. Efficiency of different antibody isotypes, complement, lung surfactant protein D, and mannan-binding lectin

The effect of opsonization of Pneumocystis carinii with different antibody classes, complement, mannan‐binding lectin (MBL), and lung surfactant protein D (SP‐D) on respiratory burst activation was studied. Antibodies were obtained by affinity chromatography, complement from a hypogammaglobulinaemic patient, and phagocytic cells from blood donors. Respiratory burst activation was measured by chemiluminescence (CL). With freshly isolated neutrophils the combination of antibodies and complement but not antibody alone, had opsonizing properties. With neutrophils cultured for 20 h, however, IgG increased the CL response. In macrophages P. carinii opsonized with IgG alone induced a CL response proportional to the antibody titre used. With IgA an effect, albeit lower, was also seen, whereas IgM alone was inefficient. The combined effect of antibodies and complement increased the response significantly for all three antibody classes, IgG and complement giving the largest response. Binding of MBL to P. carinii and Candida albicans was demonstrated; however, only the former stimulated activation of the respiratory burst. SP‐D did not bind to either microorganism and had no effect on the respiratory burst. It is concluded that IgG, IgA and complement are important opsonizing factors in infections involving P. carinii. The relative importance varies with the type of phagocytic cell studied.

The C-Reactive Protein Responses in HIV-infected Patients with Pneumonia

The acute phase C-reactive protein (CRP) was measured in serum of HIV-infected patients suffering from Pneumocystis carinii pneumonia (PCP) (32 patients), bacterial pneumonia (10 patients), and in 19 immunocompetent patients with bacterial pneumonia. The HIV-infected patients with bacterial pneumonia had a significantly lower CRP level than the immunocompetent patients (50% versus 95% had an s-CRP level > 80 mg/l). No significant difference was found in the CRP response to P. carinii or bacteria in HIV-infected patients with pneumonia due to these microorganisms (20% versus 50% had s-CRP > 80 mg/l). In the group of PCP patients, a significantly lower CRP level was found in those with CD4 positive lymphocyte counts below 50 x 10(6)/l. There was no correlation between the CRP response and the severity of the PCP as estimated by the degree of hypoxia. We conclude that the CRP level cannot be used to discriminate between PCP and bacterial pneumonia in HIV-infected patients.

Variation of a 470000 daltons antigen complex and catalase antigen in clinical isolates of Aspergillus fumigatus

Antigens in ruptured mycelium of 18 Aspergillus strains including 14 clinical isolates of A. fumigatus were studied by immunoelectrophoresis. One antigenic component of molecular weight 470 000 previously characterized by hydrophobic interaction chromatography and gel filtration and a second component with catalase activity were detected in all A. fumigatus isolates but in varying quantities. The 470 000 antigen complex cross-reacted with antigens in A. flavus and A. nidulans but not in A. niger or A. terreus. A. fumigatus catalase antigen cross-reacted with catalase in A. flavus, A. nidulans and A. terreus, but not in A. niger. One A. fumigatus isolate produced two catalase antigens showing a reaction of partial identity. A. flavus also produced two catalase antigens, one of which was species-specific.

Serum antibodies to Aspergillus fumigatus in Danish farmers

182 Danish farmers and 105 city-dwelling control subjects were investigated for serum IgG antibodies to three purified Aspergillus fumigatus antigen fractions and unfractionated culture filtrate by enzyme-linked immunosorbent assay (ELISA). Farmers had higher levels of antibodies to all four ELISA antigens than non-farming controls. In farmers and controls high antibody activity was recorded with an antigen fraction of approximate molecular weight 470 000 daltons. Antibody levels to this fraction were higher in non-smokers than smokers in both study groups. Cattle farmers had higher antibody levels to the 470 000 daltons fraction than farmers with no animals on the farm. Farmers with higher antibody activity to any of the three fractionated ELISA antigens tended to have fewer respiratory symptoms than farmers with lower antibody activity. It was concluded that occupational exposure and smoking habits are the main determinants of the immune response to A. fumigatus in man.

Plaque-forming cell capability in the senescent.

The number of plaque-forming cells (PFC) developed in pokeweed mitogen (PWM)-activated unfractionated or T/B separated, 4:1 reconstituted cultures of peripheral blood lymphocytes (PBL) with well-characterized subpopulations obtained from healthy, aged subjects was compared to that of young blood donors. The absolute number of PBL in the aged was reduced by 36%, and the percentage of sheep erythrocyte-rosette-forming cells (E-RFC) by 27%, compared to the percentage obtained in young donors. The IgM-, IgG- and IgA-immunoglobulin (Ig) secretion was monitored with a protein A PFC assay. The number of PFC in PBL cultures of the aged was 58% of the number found in cultures of the young controls. The number of PFC generated in cultures of autologous irradiated T and untreated B cells showed a 104% increase in the aged whereas a 63% increase was obtained using cells from young individuals. Co-cultures of young B cells with untreated or irradiated young or aged T cells showed a significant rise in the PFC response in cultures with irradiated aged T cells, while an equal number of PFC was generated in cultures of young B cells with young or aged untreated T cells. Our results demonstrate a decreased number of PBL, especially T cells, an impaired B cell function and a pronounced enhancement of the PFC response in cultures of irradiated aged T cells and young or aged B cells, whereas the T helper function of untreated cells was found to be normal. The influence of monocytes on the PFC response did not differ in the two groups.

Serum antibodies to Aspergillus fumigatus in patients with rheumatic diseases

IgG and IgA serum antibodies to Aspergillus fumigatus were determined in 47 patients with rheumatic disorders, 4 patients with pulmonary aspergillosis associated with rheumatic disease, and in 36 healthy controls. Antibody titres determined by indirect immunofluorescence were comparable in patients with rheumatic diseases and in controls, except for 2 patients with IgG antibody titres within the upper range of patients with aspergillosis. IgG antibody levels to 2 partially purified A. fumigatus antigens (I and VIII), determined by enzyme-linked immunosorbent assay (ELISA), were higher in rheumatic patients than in controls and with antigen VIII the difference reached statistical significance for all subgroups of rheumatic patients. IgA antibody levels by ELISA were also increased in rheumatic patients compared with the control group: IgA levels against antigen I fell within the range of patients with aspergillosis in 7 patients with rheumatic disorders. This suggests that some rheumatic patients are more strongly sensitized to Aspergillus antigens than normal subjects.