Common variable immunodeficiency classification by quantifying T-cell receptor and immunoglobulin κ-deleting recombination excision circles Chikako Kamae,

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Presentation transcript:

Common variable immunodeficiency classification by quantifying T-cell receptor and immunoglobulin κ-deleting recombination excision circles Chikako Kamae, MD, Noriko Nakagawa, MD, PhD, Hiroki Sato, MS, Kenichi Honma, MD, Noriko Mitsuiki, MD, Osamu Ohara, PhD, Hirokazu Kanegane, MD, PhD, Srdjan Pasic, MD, PhD, Qiang Pan-Hammarström, MD, PhD, Menno C. van Zelm, PhD, Tomohiro Morio, MD, PhD, Kohsuke Imai, MD, PhD, Shigeaki Nonoyama, MD, PhD Journal of Allergy and Clinical Immunology Volume 131, Issue 5, Pages 1437-1440.e5 (May 2013) DOI: 10.1016/j.jaci.2012.10.059 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Quantifying TREC and KREC classifies patients with CVID into 4 groups. Patients with CVID were classified as follows: TREC(+)/KREC(+), group A (19 patients); TREC(+)/KREC(−), group B (7 patients); TREC(−)/KREC(+), group C (8 patients); and TREC(−)/KREC(−), group D (6 patients). Undetectable, Less than 100 copies/μg DNA. Journal of Allergy and Clinical Immunology 2013 131, 1437-1440.e5DOI: (10.1016/j.jaci.2012.10.059) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Cumulative incidence of complication events per 10 patient-years differs among groups. Opportunistic infections, autoimmune diseases, and malignancies were evaluated for each patient group. Complication incidences in group D (0.98 events/10 patient-years), group C (0.63 events/10 patient-years), and group B (0.30 events/10 patient-years) were higher than in group A (0.04 events/10 patient-years). Group A versus group D: **P = .0022; group A versus C: **P = .0092; group A vs group B: P = .0692. Journal of Allergy and Clinical Immunology 2013 131, 1437-1440.e5DOI: (10.1016/j.jaci.2012.10.059) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 CD45RO+CD3+CD4+ T-cell frequency within CD4+CD3+ lymphocytes was analyzed among groups. CD45RO+CD3+CD4+ lymphocyte counts were significantly higher in groups B, C, and D compared with those in group A (P < .0001). Group A: 37% ± 16%; group B: 67% ± 13% (**P < .01); group C: 92% ± 8.2% (***P < .001); and group D: 83% ± 14% (***P < .001). Journal of Allergy and Clinical Immunology 2013 131, 1437-1440.e5DOI: (10.1016/j.jaci.2012.10.059) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 KREC levels were analyzed in genomic DNA samples extracted from peripheral blood of control subjects at different age groups (n = 158; age range, 1 month to 55 years). KREC levels were significantly higher in infants (17.9 ± 3.9 × 103 copies/μg DNA) compared with other children’s age groups (8.9 ± 1.3 × 103 copies/μg DNA in the 1- to 6-year-old group and 3.6 ± 3.8 × 103 copies/μg DNA in the 7- to 18-year-old group) and adults (2.0 ± 3.3 × 103 copies/μg DNA; P < .0001). Journal of Allergy and Clinical Immunology 2013 131, 1437-1440.e5DOI: (10.1016/j.jaci.2012.10.059) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Patients were classified in the following way and analyzed for cumulative incidence of complications: A, Freiburg; B, Paris; and C, EUROclass classifications, according to CD38hiIgMhi transitional B cells (Fig E3, A-C) or CD21low B cells (D). Five patients were excluded from the Freiburg and Paris classifications because of decreased B-cell numbers (<1%). Additionally, we excluded 4 patients in the Freiburg classification, 1 patient in the Paris classification, and 4 patients in the EUROclass classification for transitional B cells and 8 in the EUROclass classification for CD21low B cells because of lack of data. The following cumulative events/10 patient-years were found. Freiburg classification: 1a, 0.36; 1b, 0.48; 2, 0.32. Paris classification: MB0, 0.50; MB1, 0.37; MB2, 0.28. EUROclass classification according to transitional B cells: B−, 0.27; smB+, 0.52; smB−Trnorm, 0.60; smB−Trhigh, 0.43. EUROclass classification according to CD21lo B cells: B−, 0.27; smB+21lo, 0.45; smB+21norm, 0.47; smB−21lo, 0.58; smB−21norm, 0.30. No classification showed any significantly increased events in any particular group according to calculated P values, as follows—Freiburg classification: 1a vs 2 = .898, 1b vs 2 = .479, 1a vs 1b = .838; Paris classification: MB0 vs MB2 = .179, MB1 vs MB2 = .654, MB0 vs MB1 = .764; EUROclass classification according to transitional B cells: B− vs smB+ = .298, smB−Trnorm vs smB+ = .809, smB−Trhi vs smB+ = .702, smB−Trhi vs smB−Trnorm = .641, smB−Trnorm vs B− = .329, smB−Trhi vs B− = .508; EUROclass classification according to CD21lo B cells: B− vs smB+21norm = .443, smB+21lo vs smB+21norm = .930, smB−21lo vs smB+21norm = .695, smB−21norm vs smB+21norm = .575, B− vs smB−21norm = .926, smB+21lo vs smB−21norm = .609, smB−21lo vs smB−21norm = .399, B− vs smB+21lo = 0.474, B− vs smB−21lo = 0.270, smB+21lo vs smB−21lo = 0.618. Journal of Allergy and Clinical Immunology 2013 131, 1437-1440.e5DOI: (10.1016/j.jaci.2012.10.059) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Comparing longitudinal cumulative incidence of complication events among groups. Cumulative incidence was estimated separately and longitudinally by using the Kaplan-Meier method and statistically compared between groups by using the log-rank test. The cumulative incidence of opportunistic infections (A), autoimmune diseases (B), malignancies (C), and all events (D) is shown. Journal of Allergy and Clinical Immunology 2013 131, 1437-1440.e5DOI: (10.1016/j.jaci.2012.10.059) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 TREC and KREC quantification classifies patients with SCID, AT, NBS, or ataxia-telangiectasia–like disease (ATLD) into 4 groups. A, Patients with B+SCID (n = 20) were classified as group C, and patients with B−SCID (n = 8) were classified as group D; these patients were included in the previous studies.5,6 B, Although most patients with AT (n = 23) and patients with NBS (n = 4) were classified as group D, TRECs were detected in peripheral blood samples (n = 4 in patients with AT and n = 2 in patients with NBS) and neonatal Guthrie cards (n = 3) of some patients with AT, who were classified as group B. Patients with ATLD with MRE11A mutations were classified as group A. Journal of Allergy and Clinical Immunology 2013 131, 1437-1440.e5DOI: (10.1016/j.jaci.2012.10.059) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions