| 1. |
- Karlsson, Isabella, et al.
(författare)
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The Fate of a Hapten - From the Skin to Modification of Macrophage Migration Inhibitory Factor (MIF) in Lymph Nodes
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Skin (contact) allergy, the most prevalent form of immunotoxicity in humans, is caused by low molecular weight chemicals (haptens) that penetrate stratum corneum and modify endogenous proteins. The fate of haptens after cutaneous absorption, especially what protein(s) they react with, is largely unknown. In this study the fluorescent hapten tetramethylrhodamine isothiocyanate (TRITC) was used to identify hapten-protein conjugates in the local lymph nodes after topical application, as they play a key role in activation of the adaptive immune system. TRITC interacted with dendritic cells but also with T and B cells in the lymph nodes as shown by flow cytometry. Identification of the most abundant TRITC-modified protein in lymph nodes by tandem mass spectrometry revealed TRITC-modification of the N-terminal proline of macrophage migration inhibitory factor (MIF) - an evolutionary well-conserved protein involved in cell-mediated immunity and inflammation. This is the first time a hapten-modified protein has been identified in lymph nodes after topical administration of the hapten. Most haptens are electrophiles and can therefore modify the N-terminal proline of MIF, which has an unusually reactive amino group under physiological conditions; thus, modification of MIF by haptens may have an immunomodulating role in contact allergy as well as in other immunotoxicity reactions.
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| 2. |
- Thorarinsdottir, Katrin, et al.
(författare)
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CD21(-/low) B cells associate with joint damage in rheumatoid arthritis patients
- 2019
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 90:2
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Tidskriftsartikel (refereegranskat)abstract
- Depletion of B cells is beneficial in rheumatoid arthritis (RA) patients with autoantibodies to citrullinated proteins (ACPA) and/or the Fc portion of immunoglobulins (rheumatoid factor [RF]), suggesting a role for B cells in disease pathogenesis. To date, however, the identity of specifically pathogenic B cell subsets has not been discovered. One candidate population is identified by the low expression or absence of complement receptor 2 (CD21(-/low) B cells). In this study, we sought to determine whether there was any correlation between CD21(-/low) B cells and clinical outcome in patients with established RA, either ACPA(+)/RF+ (n = 27) or ACPA(-)/RF- (n = 10). Healthy donors (n = 17) were included as controls. The proportion of the CD21(-/low) CD27(-)IgD(-) memory B cell subset in peripheral blood (PB) was significantly increased in ACPA(+)/RF+ RA patients compared with healthy donors, and the frequency of this subset correlated with joint destruction (r = 0.57, P < 0.04). The levels of the chemokines CXCL-9 and CXCL-10 were higher in synovial fluid than in plasma, and PB CD21(-/low) cells expressed the receptor, CXCR3. In synovial fluid, most of the B cells were CD21(-/low), approximately 40% of that population was CD27(-)IgD(-), and a third of those expressed the pro-osteoclastogenic factor receptor activator of the nuclear factor kappa B ligand (RANKL). This subset also secreted RANKL, in addition to other factors such as IL-6, even in the absence of stimulation. We interpret these data as reason to propose the hypothesis that the CD27(-)IgD(-) subset of CD21(-/low) B cells may mediate joint destruction in patients with ACPA(+)/RF+ RA.
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