IgG subclasses and neonatal infections with group B streptococci.
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Biomedical subjects
Publications and source records attributed to P Christensen.
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Previous work has shown that IgG rheumatoid factors (RF) bind to the C gamma 2-C gamma 3 interface region of human IgG in the same area that binds staphylococcal protein A (SPA). Group A, C, and G strains of Streptococci possess Fc receptors that bind to IgG but not to fragments containing only the C gamma 2 or C gamma 3 domains. This work describes the binding site location on human IgG for the binding of the isolated Fc receptor from the T15 strain of a Group A streptococcus and its relationship to the site that binds SPA and the IgG RF. The isolated T15 Fc receptor (T15) with a molecular mass of 29.5 kD inhibited the binding of IgG RF to IgG. The binding of T15 itself to IgG was strongly inhibited by SPA (42.0 kD) and its monovalent fragment D (7 kD). Human IgG fragments consisting of the C gamma 3 domains did not inhibit the binding of T15 to IgG, whereas those with both domains were effective inhibitors. T15 did not bind to rabbit IgG fragments consisting of either the C gamma 2 or C gamma 3 domains, but did bind to those with both domains. An IgG3 myeloma protein was a poor inhibitor and has been shown to bind poorly to the IgG RF. Most IgG3 myeloma proteins did not bind to SPA. The substitution of Arg and Phe for His 435 and Tyr 436 is responsible for the poor binding of IgG3 to SPA and to the IgG RF. Chemical modification of His or Tyr on IgG reduced its ability to inhibit the binding of T15 to IgG. Reversal of the chemical modifications with hydroxylamine resulted in near complete restoration of inhibitory capacity. This information, collectively, coupled with the known positions in space of the His and Tyr residues in the C gamma 2-C gamma 3 interface region, verified that both His 435 and Tyr 436, and possibly His 310 and 433, are involved. These residues are also involved in binding SPA and the IgG RF. These data therefore indicate that the T15 Group A Streptococcal Fc receptor binds to the same location on the Fc of IgG as SPA and the IgG RF. The biologic relevance of these similarities between bacterial cell wall Fc receptors and IgG RF are not yet apparent, but suggest that RF could bear the internal image of these bacterial structures.
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PGE2 and LTC4 syntheses in Ehrlich ascites cells were measured by radioimmunoassay. Hypotonic swelling results in stimulation of the leukotriene synthesis and a concomitant reduction in the prostaglandin synthesis. If the cells have access to sufficient arachidonic acid there is a parallel increase in the synthesis of both leukotrienes and prostaglandins following hypotonic exposure. PGE2 significantly inhibits regulatory volume decrease (RVD) following hypotonic swelling in Na-containing medium but not in Na-free media, supporting the hypothesis that the effect of PGE2 is on the Na permeability. PGE2 also had no effect on RVD in Na-free media in the presence of the cation ionophore gramicidin. Since the Cl permeability becomes rate limiting for RVD in the presence of gramicidin, whereas the K permeability is rate limiting in its absence, it is concluded that PGE2 neither affects Cl nor K permeability. Addition of LTD4 accelerates RVD and since the K permeability is rate limiting for RVD this shows that LTD4 stimulates the K permeability. Inhibition of the leukotriene synthesis by nordihydroguaiaretic acid inhibits RVD even when a high K conductance has been ensured by the presence of gramicidin. It is, therefore, proposed that an increase in leukotriene synthesis after hypotonic swelling is involved also in the activation of the Cl transport pathway.
The effect of vaginal washing with chlorhexidine acetate, 2 g/l at delivery, on the colonization of the urogenital tract with group B streptococci (GBS) 4 days later was investigated. Patients who were culture-positive for GBS in urethra and/or cervix in pregnancy weeks 32 and 36 as well as at delivery were included in a prospective study. The washing procedure was performed in 31 parturients, and 10 (32%) were culture-negative at day 4 after delivery. In contrast, only 7/47 (15%) non-washed controls were negative at day 4 (p = 0.044). The results demonstrate a prolonged suppressive effect of vaginal washing with chlorhexidine on the recovery of GBS from the urogenital tract in this highly selected patient group.
A commercial kit for the detection of group B streptococci (GBS-Test) is described. The test is based on orange pigment production after 2 days' incubation at 37 degrees C. It showed a 100% specificity and a sensitivity superior to that of a conventional selective broth method.
Urinary excretion of prostaglandin E2 (PGE2 and F2 alpha (PGF2 alpha) and plasma concentration of arginine vasopressin (AVP) were determined during urinary concentrating and diluting tests in renal transplant recipients and control subjects. During the concentrating test PGE2 and PGF2 alpha remained unchanged in the renal transplant recipients, whereas both PGE2 and PGF2 alpha were significantly reduced in the control subjects. During the diluting test PGE2 and PGF2 alpha increased in both groups but, contrary to PGF2 alpha, PGE2 was significantly higher in all periods in the transplant recipients compared to the controls. However, the prostaglandin excretion rates per kidney were significantly higher in the renal transplant recipients than control subjects, for all periods during both the concentrating and the diluting test. Arginine vasopressin was significantly higher in renal transplant recipients than control subjects during basal conditions, increased to a significantly higher level in the transplant recipients after thirst, but was reduced to the same levels in the two groups during the diluting test. It is concluded that the increased excretion of prostaglandins in renal transplant recipients may be a compensatory phenomenon representing an adaptation to a reduced renal mass in order to maintain adequate renal water excretion. Although a direct relationship between the prostaglandin excretions of PGE2 and PGF2 alpha and AVP does not seem to exist, it is possible that the higher prostaglandin excretion in the renal transplant recipients may be a counterbalancing mechanism to the higher AVP level, which most likely is secondary to a decreased responsiveness to vasopressin of the renal collecting ducts in the transplanted kidney.
Radiolabelled monoclonal IgM rheumatoid factors, four from patients with type II essential cryoglobulinaemia and one originating from a patient with rheumatoid arthritis, were tested for binding to group A, B, C and G streptococci and Escherichia coli. Two of the preparations exhibited different binding patterns for the streptococci, whereas the remaining three were not reactive. The binding of one of the factors to group A streptococci type 15 was inhibited by F(ab')2-fragments of anti-idiotypic antibodies but not anti-IgM Fc or F(ab')2 of normal rabbit IgG, indicating that the reaction was mediated via the antibody combining sites.
A new commercially available method (UROBACT, AB Dermaci, Sweden) for detection of bacteriuria was compared to a conventional semiquantitative bacteriological method. The kit consisted of two tubes, which were inoculated with urine in two different dilutions. Positive tests were recorded as a colour change from red to yellow in both tubes, and the test was considered negative if one or both tubes remained red. When studying 556 urine samples, the test detected 153 of 163 samples with greater than or equal to 10(5) colony forming units (CFU) of bacteria per ml, i.e. the sensitivity was 93.9%. Among the samples containing less than 10(5) CFU/ml, 347 of 357 were recorded as negative, giving a specificity of 97.2%. Although relatively few urine samples containing Staphylococcus saprophyticus and Pseudomonas pyoceanea were tested the results indicated that the method was less reliable for these species. However, compared to dip-slides, which also give poor results with S. saprophyticus, the new test has several advantages, including a more simple interpretation, i.e. a distinct colour change.
The single-breath method of Kim et al. for noninvasive estimation of pulmonary blood flow utilizes the PCO2 vs. PO2 curve recorded during a prolonged expiration. The calculation of pulmonary blood flow is complicated by the nonlinearity of the expression for the PCO2 vs. PO2 curve. In previous studies of the single-breath method, this problem has been solved by using a data reduction procedure which includes transformation of the nonlinear expression into a linear plot. The disadvantage of this data reduction procedure is that the transformation utilizes the first derivative of the PCO2 vs. PO2 curve, which is very sensitive to experimental noise. In the present study, we have examined an alternative data reduction procedure in which the nonlinear expression was fitted directly to the experimental curve. At an expiration length of 15 s, the two data reduction procedures gave almost identical standard deviations of 0.57 L.min-1 on repeated determinations of the pulmonary blood flow. However, the linear data reduction procedure was much more sensitive to omission of the PCO2 vs. PO2 curve segments obtained in the last part of the prolonged expiration.
The interaction between living groups A, C and G streptococci and IgG Fc was studied using human IgG, IgG Fc and IgG Fc-intermediate (Fci) fragments, chemically modified human IgG and fragment D of staphylococcal protein A (SPA). Diethylpyrocarbonate modification of His or N-acetylimidazole modification of Tyr of human IgG resulted in the loss of its capacity to inhibit the binding of radiolabelled human IgG Fc to the group A streptococci types M1 and M55, and to the group C strain SC-1, indicating that the amino acids His and Tyr are involved in the binding. Lys seems not to participate in the binding of IgG to these bacteria, however, since reductive methylation of Lys did not reduce its inhibitory capacity. Fragment D of SPA also inhibited the binding of radiolabelled human IgG Fc to strains M1, M55 and SC-1. We have previously shown that these bacteria do not bind to IgG fragments consisting of only the C gamma 2 or C gamma 3 domains. On the basis of these results, and the known relative positions in space of the His and Tyr residues on IgG Fc, it is speculated whether streptococci with IgG Fc receptors, like SPA and rheumatoid factors, interact with IgG in the interface between the C gamma 2 and C gamma 3 domains and involve His 435 and one or more of Tyr 436, His 433 and His 310. The similarities in binding sites on IgG for RFs and these bacterial Fc binding proteins suggest structural similarities between them that may be relevant to the production of rheumatoid factors in rheumatoid arthritis.
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A rat model was used to evaluate the possible effect on experimental postsplenectomy sepsis of a human gamma-globulin preparation for intravenous use (Sandoglobulin). Sixty splenectomized male Sprague-Dawley rats were given 3 X 10(3) Streptococcus pneumoniae type 1 intravenously. Twelve of the animals received no treatment and all died, in contrast to 12 sham-operated controls which all survived the challenge. The remaining splenectomized rats were divided into four groups, each consisting of 12 animals. One group was given 120 mg human gamma-globulin twice intraperitoneally (0.3 g/kg body wt), at 18 and 42 hr, after challenge; 10 of the 12 survived, in contrast to none of the 12 in the second group receiving 120 mg human albumin instead of gamma-globulin (P = 0.00003). When the injections were delayed to 24 and 48 hr, 9/12 gamma-globulin-treated animals still survived, in contrast to 0/12 in the albumin group. These findings point to new possibilities for treatment and perhaps prevention of overwhelming postsplenectomy sepsis by administration of high doses of gamma-globulins.