Streptococcal Antibodies Research Articles

Epitopes of streptococcal M proteins that evoke antibodies that cross-react with human brain.

There is evidence suggesting that Sydenham's chorea, which is a major manifestation of acute rheumatic fever, may be mediated by streptococcal antibodies that cross-react with the brain. Our studies were undertaken to determine whether streptococcal M protein, the major virulence factor of group A streptococci, evoked antibodies that cross-react with human brain. Rabbits were immunized with pepsin-extracted M protein from rheumatogenic type 6 streptococci. Immune sera were screened for the presence of antibodies that cross-reacted with human brain by indirect immunofluorescence tests and immunoblot analyses. Type 6 M protein evoked antibodies that cross-reacted with several brain proteins and antibody binding to these proteins was completely inhibited by type 6 M protein and partially inhibited by types 5 and 19 M proteins, suggesting that these heterologous M proteins contain conserved brain-cross-reactive epitopes. Using synthetic peptides from several serotypes of M proteins, the conserved brain-cross-reactive epitopes were localized to a decapeptide contained within the covalent structure of the B repeat region of type 6 M protein. These peptides also inhibited brain-cross-reactive antibodies in the serum of a patient with active Sydenham's chorea. Our data indicate that streptococcal M proteins contain brain-cross-reactive epitopes that could potentially be involved in the pathogenesis of Sydenham's chorea.

Purpuric pityriasis rosea

An ll-year-old girl noticed several asymptomatic spots on her abdomen. The eruption spread to the remainder of her trunk and proximal extremities during the next 3 weeks. Physical examination revealed multiple, nonscaling petechiae and ecchymoses oriented along Langer's lines on the neck, trunk, and proximal extremities. Complete blood cell count, prothrombin time, partial thromboplastin! time, 16-variable automated chemistry panel and urinalysis were all normal. Antinuclear antibody, rapid plasma reagin, rickettsial profile, and streptococcal antibody titers were unremarkable. A skin biopsy specimen demonstrated a superficial and mid-dermal perivascular mononuclear cell infiltrate with erythrocyte extravasation, No foci of parakeratosis or spongiosis were seen, and there was no evidence ofvascu-

Role of heavy chain constant domains in antibody-antigen interaction. Apparent specificity differences among streptococcal IgG antibodies expressing identical variable domains.

In this report, we examine the influence of CH domains on antibody specificity, in the context of variable epitope density on bacteria and synthetic glycoconjugates. Hybridomas secreting IgG1 and IgG2b mAb, specific for the N-acetyl-glucosamine (GlcNAc) residues of streptococcal group A carbohydrate, were previously generated from a hybridoma secreting a mouse IgG3 mAb. We show that these three mAb have identical H and L chain V domains, as determined by 1) cDNA sequencing, 2) binding to soluble Ag, and 3) binding to nine monoclonal anti-idiotopes. Nevertheless, the IgG3 mAb binds more effectively than the V region-identical IgG1 or IgG2b mAb to each of three strains of group A streptococci that display different amounts of terminal GlcNAc residues on their cell walls. The magnitude of the subclass-associated differential in binding varies with the target strain, and, whereas the IgG3 mAb binds best to the strain expressing an intermediate amount of GlcNAc, the IgG1 and IgG2b mAb and IgG3-derived F(ab')2 fragments bind best to the strain expressing the highest amount of GlcNAc. The IgG3 mAb also binds better than the IgG1 and IgG2b mAb to solid-phase GlcNAc50-BSA, but the IgG2b mAb binds best to otherwise identical conjugates with lower ratios of GlcNAc to BSA (20:1, 10:1, 5:1, and 1:1). These results suggest that epitope density can significantly influence the magnitude of IgG subclass-associated binding differences, and that structural differences in the CH regions, particularly the CH2 and CH3 domains, can influence the apparent specificities of IgG molecules for multivalent Ag.

Group A streptococcal infection in an aboriginal community.

To determine whether group A streptococcal infection and poststreptococcal sequelae are still a significant health issue for Aboriginal communities. A cross-sectional survey of streptococcal carriage, infection and antibody levels. A north Queensland Aboriginal community. One hundred and twenty preschool and school-aged children (2 to 12 years of age) living in the Lockhart River Community on Cape York Peninsula. Pyoderma was present in 43% of the children and in 76% of these culture of skin lesions grew group A streptococci. Group A streptococci also grew from 13% of throat swabs, making a total of 36% of children culture positive. Anti-streptolysin O and anti-DNAase B levels were remarkably high and increased with age. The evidence presented confirms a high level of group A streptococcal carriage and infection in children of the Lockhart River Community. Further investigation of this problem is warranted in other Aboriginal communities with a view to instituting appropriate control programs.

Mycoplasma Hyosynoviae in Joints with Arthritis in Abattoir Baconers

The occurrence of Mycoplasma hyosynoviae in synovial fluid of baconers with chronic arthritis was studied at an abattoir. Cultural examination of synovial fluid samples from diseased tarsal joints of 50 animals from 42 herds yielded M. hyosynoviae in 10 cases from 8 herds. Streptococci were found in 6 cases from 6 other herds. M. hyosynoviae antigen was found in 1 of 47 of the samples, and antibody to the mycoplasma was found in 14 of 40 of the samples by ELISA test. The presence of M. hyosynoviae in a joint was usually accompanied by the corresponding antibody. In joints with streptococcal infection antibody to M. hyosynoviae could not be found.

Evidence for an immunodeficiency syndrome related to beta‐haemolytic streptococci in patients with psoriasis

AbstractInfection with beta‐haemolytic streptococci is accepted as one of the triggering factors leading to exacerbation of psoriasis. In a long‐term study lasting nine years (1982–1991) we investigated whether there is any evidence of dysfunction of humoral and cellular immune factors, and what part is played by microbial infection in this connection, with specific reference to streptococcal antigens. 110 patients with chronic psoriasis, either clinically inactive (stage 1) or active with eruptions (stage 2) and 70 healthy controls underwent the following immunologic investigations: streptococcal antibody titres, serum immunoglobulins IgM, IgA, IgG, total serum IgE, complement factors C3, C4, B and T cells, and subpopulations. The findings demonstrate that phases of inactivity are associated with a mechanism described as “Immunologic Regulation”‐activated antibacterial titres and unremarkable findings for humoral and cellular parameters. Eruptions of psoriasis are with phases of humoral and cellular deficiency; antibacterial titres are significantly elevated, serum IgM or IgA or IgG show deficient levels, C3 is activated, C4 is decreased, as are serum IgE and T4:T8 ratio. Shift in T‐cell subpopulations may depend on serum IgE concentration.The question for consideration is whether antigen‐eliminating inflammatory lesions present in immunodeficiency phases trigger the formation of circulating immune complexes. It seems probable that the pathogenicity of these immune complexes is controlled by serum factors and that they are involved in the initiation of keratinocyte hyperproliferation.

Equine glomerulonephritis and renal failure associated with complexes of Group-C streptococcal antigen and IgG antibody

A 12-year-old thoroughbred gelding died from diffuse global glomerulonephritis, 3 months after a lower respiratory infection from which Streptococcus zooepidemicus was isolated. Immunopathological studies (immunofluorescence, immunodiffusion, immunoperoxidase testing and immunoblotting) indicated the presence of an immune reactant renal disease associated with IgG antibody and streptococcal antigens.

Streptococcal infections and cytotoxic antibody cross-reactivity with HLA antigens

Streptococcal infections and cytotoxic antibody cross-reactivity with HLA antigens

Rheumatic Fever Is Back—Don't Miss It

In brief Three times in 7 weeks an active 13-year-old girl came to a sports medicine clinic complaining of joint pain. Because of a low index of suspicion, diagnosis was delayed. It was not until her third visit that a complete medical history, a high streptococcal antibody titer, and a throat culture positive for beta-hemolytic streptococci indicated a surprising diagnosis—rheumatic fever. Often elusive, the diagnosis of rheumatic fever is based on criteria proposed by Jones. Treatment is aimed at eradicating the streptococci and treating the inflammatory response and is usually followed by long-term prophylaxis.

Human Immunoglobulins for Intravenous Use: Comparison of Available Preparations for Group B Streptococcal Antibody Levels, Opsonic Activity, and Efficacy in Animal Models

Currently available human immunoglobulin preparations for intravenous use (IVIGs) are being used (with antibiotics) by some physicians for therapy of sepsis in newborns. Most neonatal sepsis and/or meningitis in this country is caused by group B Streptococcus (GBS), and most of these cases are due to type III GBS (III-GBS). The killing of III-GBS in vitro is dependent on specific IgG antibody. Adequate serum levels of specific III-GBS antibody protect the exposed newborn from the development of invasive disease. Therefore, III-GBS was used as a model to evaluate the activity of three IVIG preparations available for clinical use. Specific antibody levels, in vitro opsonophagocytic killing, and protective efficacy in animal models revealed differences in activity for III-GBS between the three IVIG preparations as well as between IVIG lots from the same manufacturer. Furthermore, it was found that the effect of IVIG using one of the assay methods may not reliably predict activity obtained using the other assays. These data document the inability to predict functional activity against a specific pathogen such as GBS on the part of a lot of IVIG chosen at random. In view of these findings and of the limited data evaluating clinical efficacy, IVIG cannot be recommended at this time for use in the therapy of infectious diseases such as neonatal sepsis.

Quantitative Measurement of Group B Streptococcal Antibodies (Serotypes la, Ib, II and III) in Human Cord Sera by the Indirect Enzyme-Linked Immunosorbent Assay

Cervical and vaginal carriage of group B streptococci (GBS) is normally associated with an appropriate immune response confining these organisms to a commensal state in this human habitat. A newly developed indirect enzyme-linked immunosorbent assay compares the antibody responses against two antigen preparations of GBS-serotypes Ia, Ib, II and III in the cord sera of cervico-vaginal GBS-carriers and non-carriers during pregnancy. Antibody responses in GBS-positive women against both antigen preparations were found to be significantly higher than in GBS-negative women (p less than 0.005). Antibody levels towards the EDTA-antigen were markedly lower than levels for the HCl-antigen thus indicating two different antibody responses.

Immunoglobulin therapy for neonatal sepsis: An overview of animal and clinical studies

Bacteria such as Escherichia coli and group B streptococci are common neonatal pathogens. Neonates infected perinatally often develop overwhelming sepsis which may rapidly progress to shock and death in just a few hours. This fulminant course suggests that immunity to these bacteria is deficient. Studies from several laboratories have shown that antibody is important in immunity to group B streptococcus. In vitro studies have demonstrated that efficient phagocytosis and killing of these bacteria by neutrophils or monocytes requires opsonic antibody. Many premature babies have decreased amounts of total serum immunoglobulin G and term babies may not have sufficient levels of group B streptococcal antibodies to be protected. Immune globulin that contains adequate opsonic antibody to group B streptococcus may therefore be of value as adjunctive therapy for treating infections with these bacteria and may reduce the morbidity and mortality associated with group B streptococcal infection in high-risk neonates. Although intravenous immune globulin has been used to both prevent and treat infections in neonates, only limited efficacy data are available. Several large, blinded, and controlled studies that are being completed and analyzed will be important to determine the role of immune globulin therapy in neonates.

A new heart-cross-reactive antigen in Streptococcus pyogenes is not M protein.

To identify tissue-cross-reactive antigens other than M protein in Streptococcus pyogenes, proteins of M-positive strains and an M-negative strain were probed in Western blots for reactivity with cross-reactive streptococcal monoclonal antibodies (MAbs) 36.2.2 and 54.2.8. A protein(s) near a molecular mass of 60 kDa in extracts of five group A streptococcal serotypes and the M-negative strain reacted with the MAbs. A study of human antibody responses to purified membranes of S. pyogenes indicated a hyperreactivity to a 60-kDa protein in acute rheumatic fever. Since MAbs 36.2.2 and 54.2.8 are known to cross-react with myosin or actin and streptococcal M protein, the data suggest that a homology or conformation is shared between the 60-kDa antigen and M protein. Therefore, the 60-kDa antigen is a new heart- or tissue-cross-reactive antigen of S. pyogenes that shares immunologic epitopes with but is distinct from M protein.

Idiotope structure and genetic diversity in anti-streptococcal group A carbohydrate antibodies.

Three cross-reactive idiotopes(Id), termed IdX, IdI-1, and Id5, that are present on free L chains from murine anti-group A streptococcal carbohydrate antibodies have been mapped; these Id distinguish between products of three homologous V kappa genes. For each determinant, sequence analysis of anti-streptococcal group A carbohydrate antibody V domains yielded small numbers of amino acids invariably associated with Id expression. Flow micro-fluorimetry was used to isolate three IdI-1- spontaneous mutants of the IdI-1+ hybridoma GAC 39; all had single amino acid changes in the L chain at position 60 and 77, all retained other Id, and all bound group A carbohydrate. Computer modeling was used to examine spatial relationships between Id. A number of the conserved Id5 and IdX residues cluster in the L chain framework region 1 around the first back loop connecting strands of the beta pleated sheets, and overlap at residue 15 (Id5, proline; IdX, leucine). This overlap accords with the mutually exclusive expression of Id5 and IdX. The IdI-1 loss variants have mutations of residues 60 or 77 on adjacent back loops, approximately 7.5 and 14 A from residue 15. Competitive inhibition of anti-IdX and anti-IdI-1 binding to antibodies expressing both Id can be attributed to steric hindrance. The framework back loops may be favored sites for cross-reactive Id expressed by products of a single V region gene. IdI-3a, an individual Id not associated with use of a particular gene segment, has been localized in part to residue 31 (hypervariable region 1) of the H chain.

Streptococcal type-specific antibody in patients with glomerulonephritis (2): Correlation to their histological types.

Using the PHA method, streptococcal type-specific antibody was studied in sera from 230 patients with various types of nephritis diagnosed by renal biopsy in order to clarify the relationship between streptococcal infection and the histological types of glomerulonephritis. Two or more serologic types of streptococcal type-specific antibodies with high titers (1:384 or more) were significantly increased in patients with MGA, FGS, PGN, endocapillary proliferative GN, MPGN and IgA GN as compared with those in healthy subjects. Two or more serologic types having high titers (1:384 or more) were significantly increased in MGA, PGN, MPGN and IgA GN as compared with MN. The highest titers (1:768 or more) of streptococcal type-specific antibodies were significantly more frequent in endocapillary proliferative GN as compared with healthy subjects, and such titers were significantly increased in endocapillary proliferative GN and MPGN as compared with MN. The frequency of detection of streptococcal serologic types having high titers (1:384 or more) as found in patients with various nephritis, was in the order of Types 18, 3, 30, 1, 12, 10, 6 and 37, and more than half of the nephritogenic types were included in these serologic types. The above data, which suggest a higher probability of contact with nephritogenic strains during alternative establishment of streptococci by different serologic types, may indicate a close relationship of streptococcal infections with MGA, PGN, MPGN, IgA GN, FGS and endocapillary proliferative GN.

掌せき膿ほう疾患者におけるへん桃陰か内細菌叢と血清中抗レンサ球菌抗体に関する検討

The purpose of this study was to clarify the relationship between bacterial flora in tonsillar lacunae and antistreptococcal antibody in sera of the patients with pustulosis palmaris et plantaris (PPP). Since the pustules develops or worsens after tonsillitis in many patients with PPP, a pathogenic role of tonsillar bacteria is suggested, but no significant association has been proven so far. In this study, the aerobes in the tonsillar lacunae were identified and quantitated in 15 adult patients with PPP and 9 adult patients with chronic tonsillitis (CT). In addition, serum streptococcal antigen-specific antibody levels in 40 adult patients with PPP, 18 adult patients with chronic tonsillitis, and 11 healthy volunteers (controls) were examined by enzyme-linked immunosorbent assay (ELISA). The results were as follows. 1. A total of 53 strains (17 species) of aerobes were isolated and identified from the tonsillar lacunae in patients with PPP, while 35 strains (12 species) of aerobes were found in the patients with CT. 2. S. salivarius and S. pneumoniae were the dominant aerobes isolated from patients with PPP or CT. 3. Although the rates of isolation for Staphylococcus and S. pneumoniae were lower in PPP patients than in CT patients, the rate for S. sanguis I was higher in PPP patients than in CT patients. 4. The percentage of alpha, gamma-streptococci to total aerobes in PPP patients was higher than in CT patients. 5. The IgG antibody titers against S. sanguis and S. mitis, and the IgM antibody titers against all streptococci investigated in PPP patients were higher than those in both CT patients and controls. 6. Moreover, both the IgG antibody titers against S. pyogenes T4 and S. sanguis I and the IgM antibody titers against S. sanguis I and S. sanguis II of the patients in which PPP markedly improved after tonsillectomy were higher than those in which PPP showed less improvement postoperatively.

Measurement of group A streptococcal M-type antibodies by enzyme-linked immunosorbent assay and comparison between the M-type and T-type antibodies.

Measurement of group A streptococcal M-type antibodies by enzyme-linked immunosorbent assay and comparison between the M-type and T-type antibodies.

Assessment of functional group B streptococcal antibodies in intravenous human immunoglobulin preparations

Five different intravenous human immunoglobulin preparations were assessed for their opsonic activity against types 1a, 1b, II, III group B streptococci (GBS) by a chemiluminescence test. Opsonic antibodies against the four GBS types were present, but there was no significant difference between the preparations. The presence of complement increased significantly the opsonic activity for types BII and BIII. Moreover, antibodies against the four GBS types were detected by ELISA with the whole bacteria as antigen. For each type of specific antibody, a close correlation was found between results obtained by ELISA and chemiluminescence in the absence of complement r=0·81, and in the presence of complement r=0·67. These data support the presence of protective antibodies GBS in intravenous immunoglobulins and the agreement of modified ELISA to their investigation.

Streptococcal antibody: as an indicator of tonsillectomy : Fujikawa, S., Hanawa, Y., Ito, H., Ohkuni, M., Todome, Y. and Ohkuni, H.Acta Oto-Laryngol. Suppl. (1988) 106/454 (286–291)

Streptococcal antibody: as an indicator of tonsillectomy : Fujikawa, S., Hanawa, Y., Ito, H., Ohkuni, M., Todome, Y. and Ohkuni, H.Acta Oto-Laryngol. Suppl. (1988) 106/454 (286–291)

Diagnosis of recurrent rheumatic heart disease and its gradation in severity

The aim of the work was to develop diagnostic criteria for recurrent rheumatic heart disease and its variants differing in severity. To solve this question we used a complex of clinical, laboratory, instrumental data, as well as the results of pathological anatomical examination. WHO criteria with determination of streptococcal antibody titers were used during examination of soles. Besides routine methods of laboratory study, the state of body's immune system was evaluated: reaction of inhibition of leukocyte migration (RTML), titer of anti-streptococcal antibodies, measures of completed and incomplete phagocytosis, activity of blood serum acid phosphatase. The type and group of streptococcus were determined in nasopharyngeal smears. ECG and Echo-CG were recorded. The state of central hemodynamics was studied with mechanocardiography according to N.N. Savitsky.