IP Library Granted Patent US 11,867,701
Granted Patent B2
US 11,867,701 · App. 16/097,104 · Granted Jan 9, 2024

Methods for prognosing crohn's disease comprising human defensin 5 (HD5)

Inventors: Thaddeus Stappenbeck (St. Louis, MO); Ta-Chiang Liu (St. Louis, MO); Kelli VanDussen (St. Louis, MO)
Assignee: Washington University
G01N33/6893C07K14/4723G01N33/5091G01N2800/065G01N2800/52
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Quick Facts
Patent No.
US 11,867,701
App. No.
16/097,104
Granted
Jan 9, 2024
Kind
B2
Abstract

The present disclosure provides methods for classifying a cell as abnormal based on HD5 protein detection as well as methods for predicting prognosis of a subject with Crohn's disease based on HD5 protein detection.

Claims (18)

1. A method of determining treatment of a subject with Crohn's disease, the method comprising:

a) detecting human defensin 5 (HD5) protein by immunostaining of HD5 in a biological sample obtained from the subject;

b) identifying the number of HD5 positive cells in the biological sample with normal or abnormal HD5 localization and/or distribution, wherein abnormal includes disordered, diminished, diffuse, excluded and enlarged granule morphology;

c) classifying the subject as having

i) a Type II phenotype if <20% of cells have abnormal HD5 localization and/or distribution, or

ii) a Type I phenotype if ≥20% of cells have abnormal HD5 localization and/or distribution and

d) administering 5-aminosalicylate, corticosteroid, azathioprine, mercaptopurine, infliximab, adalimumab, certolizumab pegol, methotrexate, cyclosporine, tacrolimus, Natalizumab, vedolizumab, ustekinumab, antibiotics, anti-diarrheals, pain relievers, iron supplements, vitamin B-12 shots, calcium supplement, vitamin D supplement, or surgical procedure to the subject classified as Type II, or administering surgical procedure and one or more of 5-am inosalicylate, corticosteroid, azathioprine, mercaptopurine, infliximab, adalimumab, certolizumab pegol, methotrexate, cyclosporine, tacrolimus, Natalizumab, vedolizumab, ustekinumab, antibiotics, anti-diarrheals, pain relievers, iron supplements, vitamin B-12 shots, calcium supplement, and vitamin D supplement to the subject classified as Type I based on the classification of the subject as determined in step c).

2. The method of claim 1 , wherein the cell is a Paneth cell.

3. The method of claim 1 , wherein the HD5 protein is detected using immunofluorescence.

4. The method of claim 1 , wherein the HD5 protein is detected with an autostainer.

5. The method of claim 1 , wherein the biological sample is a tissue biopsy.

6. The method of claim 1 , wherein:

a) disordered is abnormal distribution and size of the HD5 granules;

b) diminished is less than or equal to ten HD5 granules;

c) diffuse is a smear of HD5 within the cytoplasm with no recognizable granules;

d) excluded is the majority of HD5 granules do not contain stainable material; and

e) enlarged is HD5 megagranules.

7. The method of claim 1 , wherein the method further comprises detecting a nuclear pore protein in the biological sample.

Assignments (2)
CONFIRMATORY LICENSE Recorded Sep 20, 2021
From: WASHINGTON UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 057541/0270 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 16, 2018
From: STAPPENBECK, THADDEUS S.; LIU, TA-CHIANG; VANDUSSEN, KELLI
To: WASHINGTON UNIVERSITY
Reel/Frame 047531/0476 →
Continuity (4)
Provisional Application 62343519 · May 31, 2016
Provisional Application 62329576 · Apr 29, 2016
Provisional Application 62328386 · Apr 27, 2016
Related Publication 20210223265A1 · Jul 22, 2021