Serological Evidence of Immune Priming by Group A Streptococci in Patients with Acute Rheumatic Fever
Acute rheumatic fever (ARF) is an autoimmune response to Group A Streptococcus (GAS) infection. Repeated GAS exposures are proposed to ‘prime’ the immune system for autoimmunity. This notion of immune-priming by multiple GAS infections was first postulated in the 1960s, but direct experimental evide...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01119/full |
| _version_ | 1818355508878245888 |
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| author | Jeremy M Raynes Jeremy M Raynes Hannah RC Frost Deborah A Williamson Deborah A Williamson Deborah A Williamson Paul G Young Paul G Young Edward N Baker Edward N Baker John D Steemson Jacelyn M Loh Jacelyn M Loh Thomas Proft Thomas Proft P Rod Dunbar P Rod Dunbar Polly E Atatoa Carr Anita Bell Nicole Jane Moreland Nicole Jane Moreland |
| author_facet | Jeremy M Raynes Jeremy M Raynes Hannah RC Frost Deborah A Williamson Deborah A Williamson Deborah A Williamson Paul G Young Paul G Young Edward N Baker Edward N Baker John D Steemson Jacelyn M Loh Jacelyn M Loh Thomas Proft Thomas Proft P Rod Dunbar P Rod Dunbar Polly E Atatoa Carr Anita Bell Nicole Jane Moreland Nicole Jane Moreland |
| author_sort | Jeremy M Raynes |
| collection | DOAJ |
| description | Acute rheumatic fever (ARF) is an autoimmune response to Group A Streptococcus (GAS) infection. Repeated GAS exposures are proposed to ‘prime’ the immune system for autoimmunity. This notion of immune-priming by multiple GAS infections was first postulated in the 1960s, but direct experimental evidence to support the hypothesis has been lacking. Here we present novel methodology, based on antibody responses to GAS T‑antigens, that enables previous GAS exposures to be mapped in patient sera. T-antigens are surface expressed, type specific antigens and GAS strains fall into 18 major clades or T-types. A panel of recombinant T-antigens was generated and immunoassays were performed in parallel with serum depletion experiments allowing type-specific T‑antigen antibodies to be distinguished from cross-reactive antibodies. At least two distinct GAS exposures were detected in each of the ARF sera tested. Furthermore, no two sera had the same T-antigen reactivity profile suggesting that each patient was exposed to a unique series of GAS T‑types prior to developing ARF. The methods have provided much-needed experimental evidence to substantiate the immune-priming hypothesis, and will facilitate further serological profiling studies that explore the multifaceted interactions between GAS and the host. |
| first_indexed | 2024-12-13T19:42:26Z |
| format | Article |
| id | doaj.art-0239d17305a44fdab193de3641e8bb5f |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-13T19:42:26Z |
| publishDate | 2016-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-0239d17305a44fdab193de3641e8bb5f2022-12-21T23:33:39ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-07-01710.3389/fmicb.2016.01119196605Serological Evidence of Immune Priming by Group A Streptococci in Patients with Acute Rheumatic FeverJeremy M Raynes0Jeremy M Raynes1Hannah RC Frost2Deborah A Williamson3Deborah A Williamson4Deborah A Williamson5Paul G Young6Paul G Young7Edward N Baker8Edward N Baker9John D Steemson10Jacelyn M Loh11Jacelyn M Loh12Thomas Proft13Thomas Proft14P Rod Dunbar15P Rod Dunbar16Polly E Atatoa Carr17Anita Bell18Nicole Jane Moreland19Nicole Jane Moreland20University of AucklandUniversity of AucklandUniversity of AucklandUniversity of AucklandInstitute of Environmental Science and ResearchUniversity of MelbourneUniversity of AucklandUniversity of AucklandUniversity of AucklandUniversity of AucklandUniversity of AucklandUniversity of AucklandUniversity of AucklandUniversity of AucklandUniversity of AucklandUniversity of AucklandUniversity of AucklandWaikato District Health BoardWaikato District Health BoardUniversity of AucklandUniversity of AucklandAcute rheumatic fever (ARF) is an autoimmune response to Group A Streptococcus (GAS) infection. Repeated GAS exposures are proposed to ‘prime’ the immune system for autoimmunity. This notion of immune-priming by multiple GAS infections was first postulated in the 1960s, but direct experimental evidence to support the hypothesis has been lacking. Here we present novel methodology, based on antibody responses to GAS T‑antigens, that enables previous GAS exposures to be mapped in patient sera. T-antigens are surface expressed, type specific antigens and GAS strains fall into 18 major clades or T-types. A panel of recombinant T-antigens was generated and immunoassays were performed in parallel with serum depletion experiments allowing type-specific T‑antigen antibodies to be distinguished from cross-reactive antibodies. At least two distinct GAS exposures were detected in each of the ARF sera tested. Furthermore, no two sera had the same T-antigen reactivity profile suggesting that each patient was exposed to a unique series of GAS T‑types prior to developing ARF. The methods have provided much-needed experimental evidence to substantiate the immune-priming hypothesis, and will facilitate further serological profiling studies that explore the multifaceted interactions between GAS and the host.http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01119/fullImmunohistochemistryT-antigengroup A streptococcusimmune primingacute rheumatic fevertee-type |
| spellingShingle | Jeremy M Raynes Jeremy M Raynes Hannah RC Frost Deborah A Williamson Deborah A Williamson Deborah A Williamson Paul G Young Paul G Young Edward N Baker Edward N Baker John D Steemson Jacelyn M Loh Jacelyn M Loh Thomas Proft Thomas Proft P Rod Dunbar P Rod Dunbar Polly E Atatoa Carr Anita Bell Nicole Jane Moreland Nicole Jane Moreland Serological Evidence of Immune Priming by Group A Streptococci in Patients with Acute Rheumatic Fever Frontiers in Microbiology Immunohistochemistry T-antigen group A streptococcus immune priming acute rheumatic fever tee-type |
| title | Serological Evidence of Immune Priming by Group A Streptococci in Patients with Acute Rheumatic Fever |
| title_full | Serological Evidence of Immune Priming by Group A Streptococci in Patients with Acute Rheumatic Fever |
| title_fullStr | Serological Evidence of Immune Priming by Group A Streptococci in Patients with Acute Rheumatic Fever |
| title_full_unstemmed | Serological Evidence of Immune Priming by Group A Streptococci in Patients with Acute Rheumatic Fever |
| title_short | Serological Evidence of Immune Priming by Group A Streptococci in Patients with Acute Rheumatic Fever |
| title_sort | serological evidence of immune priming by group a streptococci in patients with acute rheumatic fever |
| topic | Immunohistochemistry T-antigen group A streptococcus immune priming acute rheumatic fever tee-type |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01119/full |
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