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AssigneeLa Jolla Institute for Allergy and Immunology
InventorsShane Crotty, Jennifer Dan
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Recurrent tonsillitis disease (RT) is a common indication for pediatric tonsillectomy, the most frequent childhood surgery. It is unknown why some children develop RT. The present disclosure demonstrates that RT tonsils exhibit significantly smaller germinal centers than non-RT tonsils, concomitant with a bias against Group A Streptococcus (GAS)-specific germinal center follicular helper CD4+ T cells (GC Tfh), and significantly reduced antibodies to the GAS virulence factor SpeA. The present disclosure also shows a significant immunogenetic component to this disease, with the identification of ‘at risk’ and ‘protective’ HLA alleles for RT. Finally, the present disclosure identifies a new cell type, granzyme B+GC Tfh cells, which are activated by SpeA, are significantly more abundant in RT GC Tfh cells, and have the capacity to kill B cells, thus, providing a window into the immunology and genetics of a classic childhood disease and identifies a new type of pathogenic T cell.
A method of treating or preventing a Streptococcus pyogenes infection in a subject, comprising eliciting, stimulating, inducing, promoting, increasing, or enhancing an immune response to Streptococcal pyrogenic exotoxin A (SpeA) in the subject.
A vaccine composition comprising Streptococcal pyrogenic exotoxin A (SpeA), or a peptide, variant, homologue, derivative or subsequence thereof, and an adjuvant.
A method of treating tonsillitis or strep throat in a subject, the method comprising administering an agent that modulates, reduces, inhibits, decreases or blocks Streptococcal pyrogenic exotoxin A (SpeA) in an amount sufficient to treat tonsillitis or strep throat in the subject.
A method of determining whether a subject has, is at risk of having, or is need of treatment for tonsillitis or strep throat, the method comprising processing a biological sample from the subject for determining the Human Leukocyte Antigen (HLA) Class II alleles present in the sample.
A method for treatment of a subject for tonsillitis or strep throat, the method comprising processing a biological sample from a subject for determining the Human Leukocyte Antigen (HLA) Class II alleles present in the sample, wherein the presence of allele HLA DBQ1*06:02 is indicative that the subject should not receive treatment for tonsillitis or strep throat and presence of one or both of alleles HLA DRB1*01:01 and HLA DRB1*07:01 is indicative that the subject should receive treatment for tonsillitis or strep throat, and treating the subject based on the determining step.
A method of determining whether a subject has, is at risk of having, or is need of treatment for tonsillitis or strep throat, comprising processing a biological sample from the subject, the sample being suspected of including germinal center T follicular helper cells, for measuring an amount of the germinal center T follicular helper cells which are specific for or responsive to Streptococcal pyrogenic exotoxin A (SpeA), and comparing the measured amount to a reference amount, wherein a lower measured amount compared to the reference amount is indicative that the subject has, is at risk of having, or is need of treatment for tonsillitis or strep throat.
A method of determining whether a subject should receive treatment for tonsillitis or strep throat, comprising processing a biological sample from the subject, the sample being suspected of including germinal center T follicular helper cells, for measuring an amount of germinal center T follicular helper cells specific for or responsive to Streptococcal pyrogenic exotoxin A (SpeA), and comparing the measured amount to a reference amount, wherein a lower measured amount compared to the reference amount is indicative that the subject should receive treatment for tonsillitis or strep throat.
A method of determining an efficacy of a treatment for tonsillitis or strep throat in a subject, the method comprising processing a biological sample from the subject, the sample being suspected of including germinal center T follicular helper cells, for measuring an amount of the germinal center T follicular helper cells specific for or responsive to Streptococcal pyrogenic exotoxin A (SpeA), and comparing the measured amount to a reference amount.
A method for treating a subject for a disease or disorder associated with impaired germinal centers, the method comprising:
A method for treatment of a subject for a disease or disorder associated with impaired germinal centers, the method comprising modulating, reducing, inhibiting, decreasing or blocking activation, differentiation, proliferation, number or activity of killer germinal center T follicular helper cells (killer GC Tfh cells).
A method for evaluating a condition status in a subject, the condition being a disease or disorder associated with impaired germinal centers, the method comprising:
A method of determining response or resistance to treatment for a disease or disorder associated with impaired germinal centers in a subject undergoing treatment for a disease or disorder associated with impaired germinal centers, the method comprising:
The method of claim 30 or 31, wherein the disease or disorder associated with impaired germinal centers is tonsillitis or strep throat.
A method for treating a subject for an autoimmune disease, the method comprising:
A method for treatment or prevention of an autoimmune disease in a subject, the method comprising modulating, increasing, enhancing, eliciting, stimulating or promoting activation, differentiation, proliferation, number or activity of killer germinal center T follicular helper cells (killer GC Tfh cells).
A method for treatment or prevention of an autoimmune disease in a subject, the method comprising administrating to the subject an effective amount of a purified killer germinal center T follicular helper cell (killer GC Tfh cell) population.
A pharmaceutical composition comprising isolated killer germinal center T follicular helper cells (killer GC Tfh cells) and a pharmaceutically acceptable carrier, wherein said killer GC Tfh cells are modified so as to have modified gene expression, modified cell function or to include a ribonucleic acid interference (RNAi)-causing molecule, or a conjugated therapeutic agent.
A method of determining whether a subject has, is at risk of having, or is need of treatment for tonsillitis or strep throat, the method comprising processing a biological sample from the subject, the sample being suspected of containing anti-Streptococcal pyrogenic exotoxin A (SpeA) antibodies, for measuring an amount of anti-SpeA antibodies in the biological sample, and comparing the measured amount of anti-SpeA antibodies to an amount of anti-SpeA antibodies in a control sample.
Dependencies are inferred from the claim text.