Dataset Information

Antibody responses to collagen peptides and streptococcal collagen-like 1 proteins in acute rheumatic fever patients.

ABSTRACT: Acute rheumatic fever (ARF) is a serious post-infectious immune sequelae of Group A streptococcus (GAS). Pathogenesis remains poorly understood, including the events associated with collagen autoantibody generation. GAS express streptococcal collagen-like proteins (Scl) that contain a collagenous domain resembling human collagen. Here, the relationship between antibody reactivity to GAS Scl proteins and human collagen in ARF was investigated. Serum IgG specific for a representative Scl protein (Scl1.1) together with collagen-I and collagen-IV mimetic peptides were quantified in ARF patients (n = 36) and healthy matched controls (n = 36). Reactivity to Scl1.1 was significantly elevated in ARF compared to controls (P < 0.0001) and this was mapped to the collagen-like region of the protein, rather than the N-terminal non-collagenous region. Reactivity to collagen-1 and collagen-IV peptides was also significantly elevated in ARF cases (P < 0.001). However, there was no correlation between Scl1.1 and collagen peptide antibody binding, and hierarchical clustering of ARF cases by IgG reactivity showed two distinct clusters, with Scl1.1 antigens in one and collagen peptides in the other, demonstrating that collagen autoantibodies are not immunologically related to those targeting Scl1.1. Thus, anti-collagen antibodies in ARF appear to be generated as part of the autoreactivity process, independent of any mimicry with GAS collagen-like proteins.

SUBMITTER: Pilapitiya DH

PROVIDER: S-EPMC8600009 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Antibody responses to collagen peptides and streptococcal collagen-like 1 proteins in acute rheumatic fever patients.

Pilapitiya Devaki H DH Harris Paul W R PWR Hanson-Manful Paulina P McGregor Reuben R Kowalczyk Renata R Raynes Jeremy M JM Carlton Lauren H LH Dobson Renwick C J RCJ Baker Michael G MG Brimble Margaret M Lukomski Slawomir S Moreland Nicole J NJ

Pathogens and disease 20210701 6

Acute rheumatic fever (ARF) is a serious post-infectious immune sequelae of Group A streptococcus (GAS). Pathogenesis remains poorly understood, including the events associated with collagen autoantibody generation. GAS express streptococcal collagen-like proteins (Scl) that contain a collagenous domain resembling human collagen. Here, the relationship between antibody reactivity to GAS Scl proteins and human collagen in ARF was investigated. Serum IgG specific for a representative Scl protein ( ...[more]

PMID: 34185083

Similar Datasets

Project description:BackgroundAcute rheumatic fever (ARF) predominantly affects indigenous Māori schoolchildren in Bay of Plenty region, and more so male Māori students, especially when socioeconomically deprived. We evaluated the effectiveness of strategies for reducing ARF with group A streptococcal pharyngitis treatment in 2011-18.MethodsWe retrospectively assessed outcomes of 3 open cohorts of Māori schoolchildren receiving different interventions: Eastern Bay rural Cohort 1, mean deprivation decile 9.80, received school-based sore-throat programs with nurse and general practice (GP) support; Eastern Whakatane township/surrounds Cohort 2, mean deprivation 7.25, GP management; Western Bay Cohort 3, mean deprivation 5.98, received predominantly GP care, but 3 highest-risk schools received school-based programs. Cases were identified from ICD10 ARF-coded hospital discharges, notifications to Ministry of Health, and a secondary-prevention penicillin database. Primary outcomes were first-presentation ARF cohorts' incidence preintervention (2000-10) and postintervention (2011-18) with cases over annual school rolls' Māori students-year denominators.ResultsOverall, ARF in Maori schoolchildren declined in the cohorts with school-based programs. Cohort 1 saw a postintervention (2011-18) decline of 60%, 148 to 59/100,000/year, rate ratio (RR) = 0.40(CI 0.22-0.73) P = 0.002. Males' incidence declined 190 to 78 × 100,000/year RR = 0.41(CI 0.19-0.85) P = 0.013 and females too, narrowing gender disparities. Cohort 3 ARF incidence decreased 48%, 50 to 26/100,000/year RR = 0.52(CI 0.27-0.99) P = 0.044. In contrast, ARF doubled in Cohort 2 students with GP-only care without school-based programs increasing 30 to 69/100,000/year RR = 2.28(CI 0.99-5.27) P = 0.047, especially for males 39/100,000/year to 107/100,000/year RR = 2.71(CI 1.00-7.33) P = 0.0405.ConclusionsSchool-based programs with indigenous Māori health workers' sore-throat swabbing and GP/Nurse support reduced first-presentation ARF incidence in Māori students in highest-risk settings.

Project description:BackgroundRheumatic heart disease (RHD) poses a major disease burden among disadvantaged populations globally. It results from acute rheumatic fever (ARF), a complication of Group A Streptococcal (GAS) infection. These conditions are acknowledged as diseases of poverty, however the role of specific social and environmental factors in GAS infection and progression to ARF/RHD is not well understood. The aim of this systematic review was to determine the association between social determinants of health and GAS infection, ARF and RHD, and the effect of interventions targeting these.MethodologyWe conducted a systematic literature review using PubMed, the Cochrane Library and Embase. Observational and experimental studies that measured: crowding, dwelling characteristics, education, employment, income, nutrition, or socioeconomic status and the relationship with GAS infection, ARF or RHD were included. Findings for each factor were assessed against the Bradford Hill criteria for evidence of causation. Study quality was assessed using a standardised tool.Principle findings1,164 publications were identified. 90 met inclusion criteria, comprising 91 individual studies. 49 (50.5%) were poor quality in relation to the specific study question. The proportion of studies reporting significant associations between socioeconomic determinants and risk of GAS infection was 57.1%, and with ARF/RHD was 50%. Crowding was the most assessed factor (14 studies with GAS infection, 36 studies with ARF/RHD) followed by socioeconomic status (6 and 36 respectively). The majority of studies assessing crowding, dwelling characteristics, education and employment status of parents or cases, and nutrition, reported a positive association with risk of GAS infection, ARF or RHD. Crowding and socioeconomic status satisfactorily met the criteria of a causal association. There was substantial heterogeneity across all key study aspects.ConclusionThe extensive literature examining the role of social determinants in GAS infection, ARF and RHD risk lacks quality. Most were observational, not interventional. Crowding as a cause of GAS infection and ARF/RHD presents a practical target for prevention actions.

Project description:BackgroundAcute rheumatic fever (ARF) is a serious sequela of Group A Streptococcus (GAS) infection associated with significant global mortality. Pathogenesis remains poorly understood, with the current prevailing hypothesis based on molecular mimicry and the notion that antibodies generated in response to GAS infection cross-react with cardiac proteins such as myosin. Contemporary investigations of the broader autoantibody response in ARF are needed to both inform pathogenesis models and identify new biomarkers for the disease.MethodsThis study has utilised a multi-platform approach to profile circulating autoantibodies in ARF. Sera from patients with ARF, matched healthy controls and patients with uncomplicated GAS pharyngitis were initially analysed for autoreactivity using high content protein arrays (Protoarray, 9000 autoantigens), and further explored using a second protein array platform (HuProt Array, 16,000 autoantigens) and 2-D gel electrophoresis of heart tissue combined with mass spectrometry. Selected autoantigens were orthogonally validated using conventional immunoassays with sera from an ARF case-control study (n=79 cases and n=89 matched healthy controls) and a related study of GAS pharyngitis (n=39) conducted in New Zealand.ResultsGlobal analysis of the protein array data showed an increase in total autoantigen reactivity in ARF patients compared with controls, as well as marked heterogeneity in the autoantibody profiles between ARF patients. Autoantigens previously implicated in ARF pathogenesis, such as myosin and collagens were detected, as were novel candidates. Disease pathway analysis revealed several autoantigens within pathways linked to arthritic and myocardial disease. Orthogonal validation of three novel autoantigens (PTPN2, DMD and ANXA6) showed significant elevation of serum antibodies in ARF (p < 0.05), and further highlighted heterogeneity with patients reactive to different combinations of the three antigens.ConclusionsThe broad yet heterogenous elevation of autoantibodies observed suggests epitope spreading, and an expansion of the autoantibody repertoire, likely plays a key role in ARF pathogenesis and disease progression. Multiple autoantigens may be needed as diagnostic biomarkers to capture this heterogeneity.

Dataset Information

Antibody responses to collagen peptides and streptococcal collagen-like 1 proteins in acute rheumatic fever patients.

Publications

Antibody responses to collagen peptides and streptococcal collagen-like 1 proteins in acute rheumatic fever patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets