US 11,517,615 B2 · Diagnosis and treatment of infection involving killer t follicular helper cells, methods of preparation, and uses thereof

Abstract

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.

Claims14

Dependent claims

A method for treatment of a subject for tonsillitis, recurrent tonsillitis, or strep throat, the method comprising:

processing a biological sample from a subject, wherein the biological sample is a tonsillar tissue or a lymph node tissue sample,
the sample being suspected of including Granzyme B+germinal center T follicular helper cells (Granzyme B+GC Tfh cells), by measuring an amount of the Granzyme B+GC Tfh cells which are specific for or responsive to Streptococcal pyrogenic exotoxin A (SpeA), and
comparing the measured amount to a reference amount obtained from a subject without strep throat or tonsillitis, wherein if the measured amount of Granzyme B+GC Tfh cells is greater than the amount in the reference amount it is indicative that the subject has, is at risk of having, or is need of treatment for tonsillitis, recurrent tonsillitis, or strep throat and
treating the subject if the measured amount of Granzyme B+GC Tfh cells is more than the amount in the reference amount based on the determining step with an agent that decreases the Granzyme B+GC Tfh cells in the subject.

1 more element

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. providing a biological sample, wherein the biological sample is a tonsillar tissue or a lymph node tissue sample, from said subject, the sample being suspected of including Granzyme B+germinal center T follicular helper cells (Granzyme B+GC Tfh cells);
b. processing the sample to determine a concentration, activation, differentiation, proliferation or activity level of said Granzyme B+GC Tfh cells in said sample;
c. comparing the concentration, activation, differentiation, proliferation or activity level to a reference level obtained from a subject without strep throat, tonsillitis or an autoimmune disease or an average measurement or value gathered from a population of healthy individuals that do not have strep throat, tonsillitis or an autoimmune disease;
d. evaluating the condition status based on at least the comparison in step (c), the condition being associated with impaired germinal centers, wherein the condition status is the disease or disorder associated with impaired germinal centers is tonsillitis, strep throat, recurrent tonsillitis, or the autoimmune disease in the subject based on Granzyme B+GC Tfh cells in said sample compared to the reference level;
and
e. further comprising treating said subject at least based on said comparison by administering an agent that modulates, increases, enhances, elicits, stimulates, promotes activation, differentiation, proliferation, number or activity of Granzyme B+killer GC Tfh cells, wherein the agent stimulates activation, differentiation, proliferation, number or activity of Granzyme B+killer GC Tfh cells so as to modulate the concentration of said Granzyme B+killer GC Tfh cells in said subject to treat the autoimmune disease.

3 more elements

Dependencies are inferred from the claim text.

Diagnosis and treatment of infection involving killer t follicular helper cells, methods of preparation, and uses thereof

Life of this patent

Diagnosis and treatment of infection involving killer t follicular helper cells, methods of preparation, and uses thereof

Life of this patent

Abstract

Claims14