Serum IL-31 levels are increased in a subset of patients with mastocytosis and correlate with disease severity in adult patients Karin Hartmann, MD,

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Presentation transcript:

Serum IL-31 levels are increased in a subset of patients with mastocytosis and correlate with disease severity in adult patients Karin Hartmann, MD, Nicola Wagner, MD, Anja Rabenhorst, MSc, Liselotte Pflanz, MD, Silke Leja, MTA, Anja Förster, MSc, Manuela Gehring, MTA, Alexander Kapp, MD, Ulrike Raap, MD Journal of Allergy and Clinical Immunology Volume 132, Issue 1, Pages 232-235.e4 (July 2013) DOI: 10.1016/j.jaci.2012.11.008 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 A, Serum IL-31 levels are increased in patients with mastocytosis (All) compared with those seen in healthy control subjects (Control). Adult patients with advanced mastocytosis categories show increased IL-31 levels compared with those with nonadvanced mastocytosis categories. Data are presented as box plots (minimum to maximum) with medians (left) and scatter dot plots with means (right). B, Adult patients with advanced disease categories show significantly increased IL-31 levels compared with those with nonadvanced disease categories when levels were compared by using Kaplan-Meier curves with the log-rank test. C, IL-31 levels (y-axis) positively correlate with tryptase serum levels (x-axis) in all adult patients with mastocytosis. Journal of Allergy and Clinical Immunology 2013 132, 232-235.e4DOI: (10.1016/j.jaci.2012.11.008) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Tryptase-positive MCs are the source of IL-31 in skin (A) and bone marrow (B) of patients with mastocytosis. Double immunofluorescence staining of paraffin-embedded skin (Fig 2, A) and bone marrow biopsy specimens (Fig 2, B) was performed with antibodies against tryptase (red) and IL-31 (green), demonstrating colocalization of both antibodies (yellow; magnification ×63 [Fig 2, A] and ×20 [Fig 2, B]). Journal of Allergy and Clinical Immunology 2013 132, 232-235.e4DOI: (10.1016/j.jaci.2012.11.008) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 A, As expected, serum tryptase levels are significantly increased in patients with mastocytosis (All, n = 50) compared with those seen in healthy control subjects (Control, n = 10). Tryptase levels in adult patients (All, n = 38) are increased compared with those seen in pediatric patients (All, n = 12), and adult patients with advanced disease categories (smoldering systemic mastocytosis [SSM], n = 5; aggressive systemic mastocytosis with associated clonal hematologic non–mast cell lineage disease [ASM-AHNMD], n = 3) show increased tryptase levels compared with those with nonadvanced disease categories (CM/ISM, n = 28; indolent systemic mastocytosis with associated clonal hematologic non–mast cell lineage disease [ISM-AHNMD], n = 2). Data are presented as box plots (minimum to maximum) with medians (left) and scatter dot plots with means (right). Statistical analysis was performed with the nonparametric Mann-Whitney U test. B, IL-31 levels (y-axis) positively correlate with tryptase levels (x-axis) in all patients with mastocytosis (n = 50). Correlation analysis was performed by using Spearman rank order correlation (Spearman r = 0.2708, P = .0572). Journal of Allergy and Clinical Immunology 2013 132, 232-235.e4DOI: (10.1016/j.jaci.2012.11.008) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Serum IL-31 levels in patients with mastocytosis subdivided according to the following clinically relevant parameters: A, Sex (n = 50, Mann-Whitney U test). B, Age at blood collection (n = 50). C, Presence of MC infiltrate in bone marrow (n = 27). D, Percentage of MC infiltrate in bone marrow (n = 27). E, IL-31 serum levels (y-axis) positively correlate with percentage of MC infiltrate in bone marrow (x-axis; n = 27; Spearman rank order correlation). F, Patients with MC infiltrates of greater than 15% show significantly increased IL-31 levels compared with those with MC infiltrates of 15% or less (n = 27; Kaplan-Meier curves using the log-rank test). G, Presence of KitD816V mutation (n = 17). H, Presence of osteopenia, osteoporosis, or osteosclerosis (n = 24). I, Duration from start of symptoms to blood collection (n = 50). J, Duration from diagnosis to blood collection (n = 50). K, Presence of pruritus (n = 50). L, Presence of anaphylaxis (n = 50). M, Presence of flush (n = 50). N, Presence of diarrhea (n = 50). O, Presence of skin lesions (n = 50). P, Intake of H1 antihistamines at blood collection (n = 50). Journal of Allergy and Clinical Immunology 2013 132, 232-235.e4DOI: (10.1016/j.jaci.2012.11.008) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Serum IL-31 levels in patients with mastocytosis subdivided according to the following clinically relevant parameters: A, Sex (n = 50, Mann-Whitney U test). B, Age at blood collection (n = 50). C, Presence of MC infiltrate in bone marrow (n = 27). D, Percentage of MC infiltrate in bone marrow (n = 27). E, IL-31 serum levels (y-axis) positively correlate with percentage of MC infiltrate in bone marrow (x-axis; n = 27; Spearman rank order correlation). F, Patients with MC infiltrates of greater than 15% show significantly increased IL-31 levels compared with those with MC infiltrates of 15% or less (n = 27; Kaplan-Meier curves using the log-rank test). G, Presence of KitD816V mutation (n = 17). H, Presence of osteopenia, osteoporosis, or osteosclerosis (n = 24). I, Duration from start of symptoms to blood collection (n = 50). J, Duration from diagnosis to blood collection (n = 50). K, Presence of pruritus (n = 50). L, Presence of anaphylaxis (n = 50). M, Presence of flush (n = 50). N, Presence of diarrhea (n = 50). O, Presence of skin lesions (n = 50). P, Intake of H1 antihistamines at blood collection (n = 50). Journal of Allergy and Clinical Immunology 2013 132, 232-235.e4DOI: (10.1016/j.jaci.2012.11.008) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions