US 12,416,632 B2
Methods and kits for evaluating clinical outcomes of autoimmune disease
Salvatore Albani, Singapore (SG); and Jing Yao Leong, Singapore (SG)
Assigned to SINGAPORE HEALTH SERVICES PTE. LTD., Singapore (SG)
Appl. No. 16/622,901
Filed by SINGAPORE HEALTH SERVICES PTE. LTD., Singapore (SG)
PCT Filed Jun. 11, 2018, PCT No. PCT/SG2018/050293
§ 371(c)(1), (2) Date Dec. 13, 2019,
PCT Pub. No. WO2018/231151, PCT Pub. Date Dec. 20, 2018.
Claims priority of application No. 10201704905R (SG), filed on Jun. 14, 2017.
Prior Publication US 2020/0408756 A1, Dec. 31, 2020
Int. Cl. G01N 33/564 (2006.01)
CPC G01N 33/564 (2013.01) [G01N 2333/525 (2013.01); G01N 2333/5412 (2013.01); G01N 2333/70514 (2013.01); G01N 2333/70521 (2013.01); G01N 2333/70589 (2013.01); G01N 2333/7158 (2013.01); G01N 2800/102 (2013.01); G01N 2800/52 (2013.01); G01N 2800/56 (2013.01)] 8 Claims
 
1. A method of evaluating a clinical outcome of an autoimmune disease in a subject, the method comprising:
isolating a T cell population comprising CD3+ CD4+ in a sample obtained from the subject;
testing the T cell population for biomarkers (i) CD45RA and TNF-alpha, and optionally CXCR5, or (ii) CD45RA and CXCR5;
determining the clinical outcome of the autoimmune disease in the subject, wherein the clinical outcome is indicated by comparing a level of the biomarker TNF-alpha and/or CXCR5 in the T cell population in relation to a predetermined level;
wherein the predetermined level is expressed in terms of a percentage of the T cell population and is obtained from T cells isolated from a population of healthy subjects or subjects that have recovered from an immunological disease;
wherein the level of the biomarker TNF-alpha and/or CXCR5 in the T cell population (a) above the predetermined level and in an absence of CD45RA indicates a flare state or an active state of the autoimmune disease; or (b) below the predetermined level and in an absence of CD45RA indicates an inactive state of the autoimmune disease;
wherein the predetermined level of the biomarker TNF-alpha in the T cell population is at least 10% of the total CD3+CD4+ T cell population; and/or wherein the predetermined level of the biomarker CXCR5 in the T cell population is at least 4% of the total CD3+CD4+ T cell population; and
(i)(a) selecting a subject determined to be in a flare state, or an active state, of the autoimmune disease, having the level of the biomarker TNF-alpha or CXCR5 in the T cell population above the predetermined level and an absence of CD45RA; and
(i)(b) treating, or continuing to treat the subject determined to be in a flare state, or an active state, of the autoimmune disease with a biologic disease modifying anti-rheumatic drug; or
(ii)(a) selecting a subject determined to be in the inactive state of the autoimmune disease, having the level of the biomarker TNF-alpha or CXCR5 in the T cell population below the predetermined level; and
(ii)(b) withdrawing, or continuing to withhold from treatment with a biologic disease modifying anti-rheumatic drug, the subject determined to be in the inactive state of the autoimmune disease; and
wherein the autoimmune disease is:
(a) a rheumatic disease;
(b) juvenile idiopathic arthritis (JIA);
(c) rheumatoid arthritis;
(d) psoriasis;
(e) psoriatic arthritis; or (f) polyarticular JIA.