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Abatacept alleviates severe autoimmune symptoms in a patient carrying a de novo variant in CTLA-4  Sangmoon Lee, MD, Jin Soo Moon, MD, PhD, Cho-Rong Lee,

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Presentation on theme: "Abatacept alleviates severe autoimmune symptoms in a patient carrying a de novo variant in CTLA-4  Sangmoon Lee, MD, Jin Soo Moon, MD, PhD, Cho-Rong Lee,"— Presentation transcript:

1 Abatacept alleviates severe autoimmune symptoms in a patient carrying a de novo variant in CTLA-4 
Sangmoon Lee, MD, Jin Soo Moon, MD, PhD, Cho-Rong Lee, MS, Hye-Eun Kim, PhD, Sun-Mi Baek, BS, Solha Hwang, MS, Gyeong Hoon Kang, MD, PhD, Jeong Kee Seo, MD, PhD, Choong Ho Shin, MD, PhD, Hyoung Jin Kang, MD, PhD, Jae Sung Ko, MD, PhD, Sung Gyoo Park, PhD, Murim Choi, PhD  Journal of Allergy and Clinical Immunology  Volume 137, Issue 1, Pages (January 2016) DOI: /j.jaci Copyright © 2015 The Authors Terms and Conditions

2 Fig 1 De novo CTLA-4 mutation in early-onset multiorgan autoimmune disease. A and B, Disease course and pedigree of the patient. C, The evolutionary conservation of the mutated reside. D, Structure of CTLA-4 homodimer (right)5 and interaction with CD80 (left).6 E, Overexpressed CTLA4P138T lost the ability to suppress IL-2 production in Jurkat cells. A.m., Alligator mississippiensis; B.t., Bos taurus; D.r., Danio rerio; G.g., Gallus gallus; H.s., Homo sapiens; M.m., Mus musculus; O.c., Oryctolagus cuniculus; X.l., Xenopus laevis. ∗∗P < .005. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

3 Fig 2 CTLA-4-Ig agent abatacept controls immune reactivity of the patient. A, Treg-cell (CD4+CD25+FOXP3+) population in healthy donors (HD) and the patient. B, CTLA-4 expression level in CD4+CD25+FOXP3+ cells. C, Quantitative RT-PCR of Treg-cell markers from the patient-isolated Treg cells. D, Concentration of cytokines from patient-derived PBMC culture supernatant. E and F, Patient blood levels of hemoglobin and platelet (gray and smoothened black lines) plotted against RBC and platelet transfusion rates (gray bars). Period and actual administration of abatacept treatment are depicted as a black line with dots. MFI, Mean fluorescence intensity. ∗P < .05 and ∗∗P < .005. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

4 Fig E1 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

5 Fig E2 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

6 Fig E3 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

7 Fig E4 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

8 Fig E5 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

9 Fig E6 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

10 Fig E7 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

11 Fig E8 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

12 Fig E9 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

13 Fig E10 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

14 Fig E11 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

15 Fig E12 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

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