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Proteomic Characterization of Immunoglobulin Content in Dermal Interstitial Fluid Maria T. Arevalo, Gabrielle M. Rizzo, Ronen Polsky, Trevor Glaros, and Phillip M. Mach J. Proteome Res., Just Accepted Manuscript • DOI: 10.1021/acs.jproteome.9b00155 • Publication Date (Web): 15 May 2019 Downloaded from http://pubs.acs.org on May 16, 2019
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Journal of Proteome Research
Proteomic Characterization of Immunoglobulin Content in Dermal Interstitial Fluid Maria T. Arévalo†‡, Gabrielle M. Rizzo§, Ronen Polsky⁋, Trevor Glaros*‡, and Phillip M. Mach*‡ † Defense ‡
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ABSTRACT Microneedles have been demonstrated to be a minimally invasive technique for sampling dermal interstitial fluid (ISF). Shotgun quantitative proteomics has already identified hundreds of proteins in ISF and quantitatively compared the proteome to matching serum and plasma. Interstitial fluid was determined to be a viable minimally invasive alternative to blood-derived fluids. In this communication, we re-examined the proteomic data from previous work to determine the diversity of immunoglobulins present compared to serum and plasma. Similar to our previous findings regarding the proteomic content across fluid types, ISF had a similar composition of IgG, IgA, IgD, and IgE antibodies as plasma or serum and lower quantities of IgM which reflects the relative concentrations of dermal tissue T-cell and B-cell populations indicating that the Igs were likely locally derived,. This work has significant implications for the utility of measuring Igs in ISF for clinical diagnosis of immunological diseases and skin infections. Data are available via ProteomeXchange with identifier PXD012658.
Keywords: proteomics, interstitial fluid, wearable sensing, microneedles, immunoglobulin
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Journal of Proteome Research
Introduction Blood and blood products are commonly used for detection, diagnosis, and surveillance of disease. Detection and diagnosis of pathogens in the blood may involve culture, isolation, and/or amplification of nucleic acids. However, diagnosis of diseases, including those not caused by etiological agents, may also be accomplished by serological analyses. Serology, as used in disease diagnostics, involves the identification of antigen-specific immunoglobulins (Igs) or antibodies. In a similar manner, serology can also be used to evaluate vaccine efficacy as the ability of vaccine to elicit antibody responses is often used as a marker of immunogenicity. Antibodies are composed of two light chains and two heavy chains that assemble into two antigen-binding regions and a single constant region,1 in a Y-shaped configuration.2 There are two types of light chains (λ and κ) and five types of heavy chains (α, δ, ε, γ, and μ).3 The two heavy chains are held together via disulfide bonds forming the trunk of the antibody, and one heavy chain is linked to one light chain by another disulfide bond forming an arm of the antibody.3 Proteolytic cleavage of antibodies at the hinge regions yields two antigen-binding Fab fragments, and the Fc constant fragment.1 While the Fab fragments are responsible for the specificity of antibodies to antigen, the Fc region mediates antibody effector functions via interaction with Fc receptors (FcR) that are expressed on the surface of leukocytes.4-5 Based on Fc regions, antibodies are divided into five main classes: IgA, IgD, IgE, IgG, and IgM,6 corresponding to heavy chains α, δ, ε, γ, and μ (Figure 1).3 IgG accounts for 75% of the Ig present in the serum and in humans it is further subdivided into four subclasses IgG1, IgG2, IgG3, and IgG4 with respective serum compositions of 67%, 22%, 7%, and 4%.7 IgA accounts for 15% of serum antibodies, and is also subdivided, but into two subclasses: IgA1 and IgA2.7 Finally, IgM is present as 10% of Igs in the circulation, while IgD (
