Proteomic Characterization of Immunoglobulin Content in Dermal Interstitial Fluid

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 with 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 Ig's were likely locally derived. This work has significant implications for the utility of measuring Ig's in ISF for the clinical diagnosis of immunological diseases and skin infections. Data are available via ProteomeXchange with identifier PXD012658.

Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

“…Samples were analyzed without depletion and a total of 422 proteins were identified (Figure 5E). The limited number of detected proteins may be due to the high complexity of the ISF biological matrix, [ 13 ] a phenomenon also reported in plasma, where half a dozen of its most abundant proteins, including albumin and immunoglobulins, represent 95% of the total protein biomarker content. [ 58 ] Thirty‐seven proteins (9%) were common to the 3 sources of biological fluid (Table S31, Supporting Information).…”

Microneedle-based devices for point-of-care infectious disease diagnostics

“…Microneedle-based biofluid extraction devices are usually coupled with downstream analysis strategies to detect the presence of a particular analyte of interest. These strategies span a wide variety of techniques from conventional lab-based detection methods 86 , 87 , 88 , 89 , 90 , 91 , 92 (including cell culture, microscopy, the polymerase chain reaction (PCR), the enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC) and proteomic analysis) to alternative analyte sensing strategies. Here, we restrict our discussion to the biofluid extraction aspect of these devices, and discuss the detection backends in Sections 2.2. and 2.3.…”

“…There is also the question of how well blood or ISF levels of given biomarkers reflect infection status. It is known that there is often a concentration difference between ISF and blood for certain biomarkers that are dependent on time and molecular size 183 , 184 , 185 . These challenges can be mitigated so long as such discrepancies are well characterised and a correlation is established.…”

The diagnostic potential of microneedles in infectious diseases

“…In late January 2020, during the peak of the lunar New Year travel season, the Chinese government took the extraordinary measure of locking down entire cities to contain a new and highly contagious viral respiratory disease. The media reports at the time provided the first indications of the unprecedented public health challenges posed by the coronavirus disease 2019 (COVID- 19) outbreak. As hospitals experienced a sudden influx of potentially infected patients, many patients waited to be seen in overcrowded hospital lounges.…”

“…Microneedles are short enough to penetrate only the superficial skin layers, avoiding nerve endings and major blood vessels, while still accessing analyte-rich interstitial fluid (ISF) or capillary blood. ISF is an attractive target because it contains many of the same constituents as blood plasma and suction blister fluid at clinically relevant concentrations [19]- [21]. Encouragingly, it has already been demonstrated in the context of drug delivery that microneedle patches are self-administrable [22]- [24], which paves the way for self-administration of microneedle-based diagnostics.…”