# US 2021/0333264 A1 · A ratio of immune cells as prognostic indicator of therapeutic success in allergen-specific immunotherapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0333264 A1 - Document ID: US20210333264A1 - Status: Published application - Kind: A1 - Application number: 16/625,503 - Filed: 2018-06-21 - Published: 2021-10-28 - Earliest claimed: 2017-06-23 - Assignees: Klinikum Rechts Der Isar Der Techischen UniversitäT MüNchen - Applicants: Klinikum Rechts Der Isar Der Techischen UniversitäT MüNchen - Inventors: CARSTEN B. SCHMIDT-WEBER; ADAM M. CHAKER; ULRICH M. ZISSLER; CONSTANZE A. JAKWERTH - Web page: https://patentgrep.com/patent/US20210333264A1 ## CPC - G01N 33/505: {involving T-cells} - G01N 33/6869: {Interleukin} - G01N 2800/24: Immunology or allergic disorders - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract The present invention relates to a ratio of immune cells for use in a method of predicting therapeutic success of an allergen-specific immunotherapy (AIT) in a patient suffering from or having a disposition to develop an allergic disease. Furthermore, the present invention also relates to a kit for predicting therapeutic success of an allergen-specific immunotherapy in a patient suffering from or having a disposition to develop an allergic disease. Furthermore, the present invention relates to a method of predicting therapeutic success of an allergen-specific immunotherapy (AIT) in a patient suffering from or having a disposition to develop an allergic disease. ## Claims ### Claim 1 A method of predicting therapeutic success of an allergen-specific immunotherapy (AIT) in a patient suffering from or having a disposition to develop an allergic disease selected from hay fever, allergic rhinitis, allergic asthma, allergic conjunctivitis, food allergy and stinging insect hypersensitivity, wherein said method comprises the steps: determining a ratio of interleukin-10 producing regulatory B-cells (IL-10+ Bregs) and interleukin-17 producing T-helper cells (Th17) of said patient, said ratio being represented by IL-10+ Bregs/Th17, predicting therapeutic success of an allergen-specific immunotherapy in said patient, if said determined ratio exceeds a defined threshold. ### Claim 2 (depends on 1) The method according to claim 1, wherein said allergen-specific immunotherapy comprises an initial induction phase, wherein an allergen is repeatedly administered to a patient in increasing doses of said allergen up to a maximum dose effective to induce immunologic tolerance to said allergen in said patient, and a maintenance phase, wherein said allergen is administered repeatedly to said patient at said maximum dose, and wherein, in said method, said ratio is determined in the first 1-7 weeks of the maintenance phase after the initial induction phase. ### Claim 3 (depends on 1) The method according to claim 1, wherein said allergen-specific immunotherapy involves subcutaneous injection of an allergen and comprises an initial induction phase, where said allergen is repeatedly subcutaneously administered to a patient in increasing doses of said allergen up to a maximum dose effective to induce immunologic tolerance to said allergen in said patient, and a maintenance phase, wherein said allergen is subcutaneously administered repeatedly to said patient at said maximum dose, wherein said maintenance phase comprises a first subphase (“top dose phase”) wherein said allergen is subcutaneously administered repeatedly at said maximum dose in a weekly or biweekly interval, and a second subphase (“treatment maintenance phase”), wherein said allergen is subcutaneously administered repeatedly at the same maximum dose in intervals longer than during the top-dose phase, wherein said ratio is determined 4-10 hours after administration of any maximum dose of said top-dose phase. ### Claim 4 (depends on 1) The method according to claim 1, wherein said allergen-specific immunotherapy involves sublingual administration of an allergen and comprises an initial induction phase, where said allergen is sublingually administered to a patient in increasing doses of said allergen up to a maximum dose effective to induce immunologic tolerance to said allergen in said patient, and a maintenance phase, wherein said allergen is repeatedly sublingually administered to said patient at said maximum dose, wherein said ratio is determined within the first 1-7 weeks of said maintenance phase. ### Claim 5 (depends on 1) The method according to claim 1, wherein said ratio is determined in one or several samples obtained from said patient, said sample(s) being selected from whole blood, peripheral blood mononuclear cells (PBMCs), nasal cells obtained from nasal scrapings or a nasal biopsy of said patient, bronchial cells obtained from sputum, a lung biopsy or bronchial alveolar lavage fluid (BALF) of said patient. ### Claim 6 (depends on 1) The method according to claim 1, wherein therapeutic success is measured by a patient-assessed retrospective assessment of seasonal allergic symptoms (RAAS), or by combined symptom medication score (CSMS) or by visual analog scale (VAS). ### Claim 7 (depends on 1) The method according to claim 1, wherein said ratio IL-10+ Bregs/Th17 is a ratio of gene expression signatures of IL-10+ Bregs versus gene expression signatures of Th17 and is determined by determining gene expression signatures of IL-10+ Bregs versus gene expression signatures of Th17 cells. ### Claim 8 (depends on 1) The method according to claim 1, wherein said ratio of interleukin-10 producing regulatory B-cells (IL-10+ Bregs) and interleukin-17 producing T-helper cells (Th17), represented by IL-10+ Bregs/Th17, is a ratio of cell counts of these cells. ### Claim 9 (depends on 8) The method according to claim 8, wherein said step of predicting comprises predicting therapeutic success of an allergen-specific immunotherapy in said patient, if said determined ratio of cell counts has a value in the range of ≥1.2, or comprises predicting no therapeutic success if said determined ratio of cell counts has a value in the range <1.2. ### Claim 10 (depends on 8) The method according to claim 8, wherein said method of predicting therapeutic success comprises determining said ratio of cell counts, IL-10+ Bregs/Th17, and said ratio of cell counts is determined by determining relative cell counts for both IL-10+ Bregs and Th17 cells and by subsequently calculating the ratio of these relative cell counts, wherein said relative cell count of IL-10+ Bregs cells is determined as number of IL-10+ Bregs with reference to the number of live CD19+ B-cells, and wherein said relative cell count of Th17 cells is determined as number of Th17 cells with reference to the number of live CD4+ CD3+ T-cells. ### Claim 11 (depends on 1) The method according to claim 1, wherein said cell counts of IL-10+ Bregs and of Th17 cells are determined by a method selected from flow cytometry, fluorescence-activated cell sorting (FACS), determining cell counts by means of a Coulter counter, haemocytometer, image analysis or spectrophotometry. ### Claim 12 (depends on 1) The method according to claim 1. wherein said method of predicting therapeutic success of an allergen-specific immunotherapy is an in-vitro method. ### Claim 13 (depends on 1) The method according to claim 1, wherein said allergic disease is selected from allergic rhinitis, hay fever and allergic asthma, and wherein said allergen is selected from pollen fungi, fungal spores, dust, mites, and animal dander. ### Claim 14 A kit for predicting therapeutic success of an allergen-specific immunotherapy (AIT) in a patient suffering from or having a disposition to develop an allergic disease selected from hay fever, allergic rhinitis, allergic asthma, allergic conjunctivitis, food allergy and stinging insect hypersensitivity, said kit comprising: means to obtain a sample from said patient suffering from or having a disposition to develop an allergic disease, said sample being selected from whole blood, peripheral blood mononuclear cells (PBMCs), nasal cells obtained from nasal scrapings or a nasal biopsy of said patient, bronchial cells obtained from sputum, a lung biopsy or bronchial alveolar lavage fluid (BALF) of said patient; means to perform a quantitative determination of gene expression signatures or cell counts of interleukin-10 producing regulatory B-cells (IL-10+ Bregs) and interleukin-17 producing T-helper cells (Th17) in said sample, wherein said cell counts of IL-10+ Bregs and Th17 are relative cell counts, wherein said relative cell count of IL-10+ Bregs cells is determined as number of IL-10 Bregs with reference to the number of live CD19+ B-cells, and wherein said relative cell count of Th17 cells is determined as number or Th17 cells with reference to the number of live CD4+ CD3+ T-cells. ### Claim 15 (depends on 14) The kit according to claim 14, further comprising: means to determine a ratio of gene expression signatures or cell counts of IL-10+ Bregs and Th17. ### Claim 16 (depends on 14) The kit according to claim 14, further comprising: a set of instructions for use of said kit, said instructions indicating a threshold, wherein, if a determined ratio is ≥ said threshold, such ratio indicates therapeutic success of an allergen-specific immunotherapy, and if a determined ratio is < said threshold, such ratio indicates no therapeutic success of an allergen-specific immunotherapy. ### Claim 17 (depends on 16) The kit according to claim 16, wherein said ratio is a ratio of cell counts and said threshold is 1.2. ### Claim 18 (depends on 3) The method, according to claim 3, wherein said ratio is determined 4-10 hours after administration of the last maximum dose of said top-dose phase. ### Claim 19 (depends on 4) The method, according to claim 4, wherein said ratio is determined 4-10 hours after administration of any maximum dose of said maintenance phase within said first 1-7 weeks of said maintenance phase. ### Claim 20 (depends on 7) The method, according to claim 7, wherein gene expression signatures are determined by a method selected from transcriptome-based assays, real time PCR and protein detection methods.