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Structural and immunologic cross-reactivity among filarial and mite tropomyosin: Implications for the hygiene hypothesis  Helton C. Santiago, MD, PhD,

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Presentation on theme: "Structural and immunologic cross-reactivity among filarial and mite tropomyosin: Implications for the hygiene hypothesis  Helton C. Santiago, MD, PhD,"— Presentation transcript:

1 Structural and immunologic cross-reactivity among filarial and mite tropomyosin: Implications for the hygiene hypothesis  Helton C. Santiago, MD, PhD, Sasisekhar Bennuru, PhD, Alexis Boyd, MSc, Mark Eberhard, PhD, Thomas B. Nutman, MD  Journal of Allergy and Clinical Immunology  Volume 127, Issue 2, Pages (February 2011) DOI: /j.jaci Copyright © Terms and Conditions

2 Fig 1 A, Protein sequences of tropomyosin of helminths, mites, cockroaches, and crustaceans were aligned. Identical amino acids have 1-letter codes and are black. Conserved amino acid groups are gray; nonconserved amino acids are nonshaded dots. Red letters show conserved N-terminus and tropomyosin signature sequences. B, Phylogenetic tree showing distances among tropomyosin family groups. C, 3-dimensional structure predicted for OvTrop and Der p 10 with Rosetta and Swissmodel. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © Terms and Conditions

3 Fig 2 Increased prevalence of anti–Der p 10 antibodies in Fil+ subjects. Anti-OvTrop and anti–Der p 10 antibodies were measured in Ni-NA, Ni-A, Fil-NA, and Fil-A. Dots, Individual levels for IgE and IgG4 (serum dilution 1:25) and IgG (1:400). Dotted lines, GM + 3 SD of normal controls for each ELISA (set as cutoff values for assay). Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © Terms and Conditions

4 Fig 3 A, Correlation between anti-OvTrop (y-axis) and anti–Der p 10 (x-axis) IgE (left), IgG (middle), and IgG4 (right); each point represents an individual. B, Results of depletion by Der p 10 (closed circles), OvTrop (open circles), or control antigen (closed triangles) on IgE (left), IgG (middle), and IgG4 (right) responses to Der p 10 as a function of serum dilution. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © Terms and Conditions

5 Fig 4 Der p 10 and OvTrop are functionally indistinguishable for eliciting IgE-mediated responses. Basophils sensitized with sera of atopic and Fil+ (#1 and #2) or atopic but Fil– (#3) individuals were stimulated with increasing concentrations of Der p 10 or OvTrop. Insert, Donor basophils activated with antihuman IgE before and after IgE stripping and after IgE sensitization. Histamine release as function of antigen concentration is expressed as the percentage of maximum histamine content. Pt, Patient. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © Terms and Conditions

6 Fig 5 Cross-reactive IgE develops in nonhuman primates infected with L loa. Infected monkeys (n = 4) were bled before infection and at various time points after infection; uninfected control monkeys (n = 3) were bled at the same time points. Left, Preinfection levels (dots represent each animal); right, percentage increase in specific IgE levels over background (bars represent GM + SE). Preinf, Preinfection. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © Terms and Conditions

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