# US 2021/0239678 A1 · Leukocyte recruitment in infectious disease

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- Number: US 2021/0239678 A1
- Document ID: US20210239678A1
- Status: Published application
- Kind: A1
- Application number: 17/048,656
- Filed: 2019-04-18
- Published: 2021-08-05
- Earliest claimed: 2018-04-19
- Assignees: Stickycell Pty Ltd
- Applicants: Stickycell Pty Ltd
- Inventors: Qiang Cheng; Anqi Li; Karina Islas Rios; Erick Vargas-Ordaz
- Web page: https://patentgrep.com/patent/US20210239678A1

## CPC

- G01N 33/49: Blood {(chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80)}
- G01N 33/56972: {White blood cells}
- G01N 33/5029: {on cell motility}
- G01N 33/5032: {on intercellular interactions}
- G01N 33/5091: {for testing the pathological state of an organism}
- G01N 2333/47: Assays involving proteins of known structure or function as defined in the subgroups
- G01N 2333/5421: IL-8
- G01N 2333/70525: ICAM molecules, e.g. CD50, CD54, CD102
- G01N 2333/70564: Selectins, e.g. CD62
- G01N 2496/00: Reference solutions for assays of biological material
- G01N 2800/26: Infectious diseases, e.g. generalised sepsis
- 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 disclosure relates to assays, including but not limited to, leukocyte adhesive function assays (LAFA), devices and/or methods of using such assays. The present disclosure also relates to the uses of the disclosed embodiment in diagnostic, analytic and/or prognostic applications, particularly for diagnostic, analytic and/or prognostic applications in relation to diseases associated with abnormal host immune responses.

## Claims

### Claim 1

A method to discriminate between an infectious and non-infectious inflammatory immune response in a subject, the method comprising:
subjecting a blood sample from the subject to at least one leukocyte function assay (LAFA), wherein the LAFA assesses leukocyte recruitment, adhesion and/or migration to at least one endothelial cell molecule; and
based at least in part on one or more results of the at least one LAFA, determine whether the subject has an infectious inflammatory immune response or a non-infectious inflammatory immune response.

### Claim 2 (depends on 1)

The method of claim 1, wherein the at least one LAFA quantitatively and/or semi-quantitatively assesses leukocyte recruitment, adhesion and/or migration.

### Claim 3

(canceled)

### Claim 4 (depends on 1)

The method of claim 1, wherein the at least one endothelial cell molecule is selected from VCAM-1, MadCAM-1, IL-8, SDF-1α, E-Selectin, P-Selectin and ICAM-1.

### Claim 5

(canceled)

### Claim 6 (depends on 1)

The method of claim 1, wherein the at least one LAFA measures one or more of the following parameters: a quantification of rolling leukocyte cells detected, a quantification of adhesion leukocyte cells detected, a quantification of crawling cells detected, an average speed of individual leukocyte cells detected, an average straightness of individual leukocyte cells detected, an average displacement of individual leukocyte cells detected and an average dwell time of individual cells detected.

### Claim 7 (depends on 1)

The method of claim 1, wherein the results of the at least one LAFA from the blood sample from the subject is used as a reference level for generating one or more parameters that are used for generating one or more indexes.

### Claim 8 (depends on 8)

The method of claim 8, wherein the results of the at least one LAFA from at least one healthy blood sample is used as a reference level for generating one or more parameters that are used of generating one or more indexes.

### Claim 9 (depends on 1)

The method of claim 1, wherein an activation potential ratio of the subject's blood is generated based on the results of at least one LAFA from the blood of the subject divided by the results of at least one LAFA from a Mn2+ treated blood sample of the subject.

### Claim 10 (depends on 1)

The method of claim 1, wherein the method further comprises detecting one or more leukocyte cell surface markers.

### Claim at position 11

-17. (canceled)

### Claim 18 (depends on 1)

The method of claim 1, wherein a LAFA result comprising:
i) a higher or lower level of recruited and/or adhesive leukocytes;
ii) a higher or lower percentage of recruited and/or adhesive neutrophils; and/or
iii) a higher or lower level of recruited and/or adhesive monocytes,
as compared to the reference level is indicative of sepsis, wherein the reference level is derived from a population of subjects known to have non-infectious SIRS.

### Claim 19 (depends on 1)

The method of claim 1, wherein the method comprises determining that the subject has an infectious inflammatory immune response and administering an antimicrobial or antiviral composition to the subject.

### Claim 20 (depends on 1)

The method of claim 1, wherein the method comprises determining that the subject has a non-infectious inflammatory immune response and administering an anti-inflammatory composition to the subject.

### Claim 21 (depends on 1)

method of claim 1, wherein the method comprises determining that the subject has a non-infectious inflammatory response and administering to the subject a drug capable of altering leukocyte recruitment, adhesion and/or migration.

### Claim 22 (depends on 21)

The method of claim 21, wherein the drug is an antibody that interferes with the binding of a leukocyte adhesion molecule to an endothelial cell molecule.

### Claim 23 (depends on 1)

A method of treating an infectious inflammatory immune response in a subject, the method comprising performing the method according to claim 1 and determining that the subject has an infectious inflammatory immune response, and treating the subject for the infectious inflammatory immune response.

### Claim 24 (depends on 23)

The method of claim 23, wherein the subject has sepsis.

### Claim 25 (depends on 24)

The method of claim 24, wherein treating the subject for sepsis comprises treating the patient with one or more of an antibiotic, vasopressor and corticosteroid.

### Claim 26

A method to assess a subject's response, or potential response, to a drug suitable for treating an infectious disease, the method comprising:
subjecting a blood sample from the subject to at least one leukocyte function assay (LAFA), wherein the LAFA assesses leukocyte recruitment, adhesion and/or migration to at least one endothelial cell molecule; and
based at least in part on one or more results of the at least one LAFA, assess a patient's response, or potential response, to the drug for treating the infectious disease.

### Claim 27

A method of detecting a subset of leukocytes in a subject having an inflammatory immune response, the method comprising subjecting a blood sample from the subject to at least one leukocyte function assay (LAFA), wherein the LAFA assesses leukocyte recruitment, adhesion and/or migration to at least one endothelial cell molecule;
detecting one or more leukocyte cell surface markers, and
based at least in part on one or more results of the at least one LAFA and detection of one or more leukocyte cell surface markers, determining a subset of leukocytes associated with the inflammatory immune response.

### Claim 28 (depends on 27)

The method of claim 27, wherein the subject has an inflammatory condition or infectious disease.

### Claim 29 (depends on 27)

The method of claim 27, wherein the subject has, or is suspected of having, SIRS or sepsis.

### Claim at position 24

-50. (canceled)