Summary
This review takes the reader through 45 years of islet autoantibody research, from the discovery of islet‐cell antibodies in 1974 to today’s population‐based screening for presymptomatic ...early‐stage type 1 diabetes. The review emphasizes the current practical value of, and factors to be considered in, the measurement of islet autoantibodies.
This review takes the reader through 45 years of islet autoantibody research, from the discovery of islet‐cell antibodies in 1974 to today’s population‐based screening for presymptomatic early‐stage type 1 diabetes. The review emphasizes the current practical value of, and factors to be considered in, the measurement of islet autoantibodies.
Background
Polypropylene (PP) mesh is widely used to reinforce tissues. The foreign body reaction (FBR) to the implant is dominated by innate immune cells, especially macrophages. However, ...considerable numbers of adaptive immune cells, namely T cells, have also been regularly observed, which appear to play a crucial role in the long-term host response.
Methods
This study investigated the FBR to seven human PP meshes, which were removed from the abdomen for recurrence after a median of one year. Using immunofluorescence microscopy, the FBR was examined for various innate (CD11b
+
myeloid, CD68
+
macrophages, CD56
+
NK) and adaptive immune cells (CD3
+
T, CD4
+
T-helper, CD8
+
cytotoxic, FoxP3
+
T-regulatory, CD20
+
B) as well as “conventional” immune cells (defined as cells expressing their specific immune cell marker without co-expressing CD68).
Results
T-helper cells (19%) and regulatory T-cells (25%) were present at comparable rates to macrophages, and clustered significantly toward the mesh fibers. For all cell types the lowest proportions of “conventional” cells (< 60%) were observed at the mesh–tissue interface, but increased considerably at about 50–100 µm, indicating reduced stimulation with rising distance to the mesh fibers.
Conclusion
Both innate and adaptive immune cells participate in the chronic FBR to PP meshes with T cells and macrophages being the predominant cell types, respectively. In concordance with the previous data, many cells presented a “hybrid” pattern near the mesh fibers. The complexity of the immune reaction seen within the foreign body granuloma may explain why approaches focusing on specific cell types have not been very successful in reducing the chronic FBR.
Background
Mesh implants are widely used to reinforce the abdominal wall, although the inevitable inflammatory foreign body reaction (FBR) at the interface leads to complications. Macrophages are ...suspected to regulate the subsequent scar formation, but it is still unclear whether adequate fibrous scar formation with collagen deposition depends mainly on the presence of M1 or M2 macrophages.
Methods
This study investigated the FBR to seven human polypropylene meshes, which were removed after a median incorporation time of 1 year due to the primary complaint of recurrence. Using immunofluorescence, the FBR was examined in six regional zones with increasing distance from the mesh fibers up to 350 µm, based on the cell densities, macrophage M1 (CD86) and M2 (CD163, CD206) phenotypes, deposition of collagen-I and -III, and expression of matrix metalloproteinase-2 (MMP-2) and -8 as indicator of collagen degradation.
Results
All mesh–tissue complexes demonstrated a decrease in cell density and macrophages with distance to the mesh fibers. Overall, about 60% of the macrophages presented an M2 phenotype, whereas only 6% an M1 phenotype. Over 70% of macrophages showed co-expression with collagen-I or -III and over 50% with MMP-2.
Conclusions
The chronic FBR to polypropylene meshes is associated with an M2 macrophage response, which is accompanied by collagen deposition and MMP-2 expression. These findings challenge the idea that mainly M1 macrophages are related to inflammation and highlights that iatrogenic attempts to polarize these cells towards the M2 phenotype may not be a solution to ameliorate the long-term foreign body reaction.
The Islet Autoantibody Standardization Program (IASP) aims to improve the performance of immunoassays measuring type 1 diabetes (T1D)-associated autoantibodies and the concordance of results among ...laboratories. IASP organizes international interlaboratory assay comparison studies in which blinded serum samples are distributed to participating laboratories, followed by centralized collection and analysis of results, providing participants with an unbiased comparative assessment. In this report, we describe the results of glutamic acid decarboxylase autoantibody (GADA) assays presented in the IASP 2018 workshop.
In May 2018, IASP distributed to participants uniquely coded sera from 43 new-onset T1D patients, 7 multiple autoantibody-positive nondiabetic individuals, and 90 blood donors. Results were analyzed for the following metrics: sensitivity, specificity, accuracy, area under the ROC curve (ROC-AUC), partial ROC-AUC at 95% specificity (pAUC95), and concordance of qualitative and quantitative results.
Thirty-seven laboratories submitted results from a total of 48 different GADA assays adopting 9 different formats. The median ROC-AUC and pAUC95 of all assays were 0.87 interquartile range (IQR), 0.83-0.89 and 0.036 (IQR, 0.032-0.039), respectively. Large differences in pAUC95 (range, 0.001-0.0411) were observed across assays. Of formats widely adopted, bridge ELISAs showed the best median pAUC95 (0.039; range, 0.036-0.041).
Several novel assay formats submitted to this study showed heterogeneous performance. In 2018, the majority of the best performing GADA immunoassays consisted of novel or established nonradioactive tests that proved on a par or superior to the radiobinding assay, the previous gold standard assay format for GADA measurement.
We perform a systematic study of the α-particle excitation from its ground state 0_{1}^{+} to the 0_{2}^{+} resonance. The so-called monopole transition form factor is investigated via an electron ...scattering experiment in a broad Q^{2} range (from 0.5 to 5.0 fm^{-2}). The precision of the new data dramatically supersedes that of older sets of data, each covering only a portion of the Q^{2} range. The new data allow the determination of two coefficients in a low-momentum expansion, leading to a new puzzle. By confronting experiment to state-of-the-art theoretical calculations, we observe that modern nuclear forces, including those derived within chiral effective field theory that are well tested on a variety of observables, fail to reproduce the excitation of the α particle.
A cryogenic supersonic gas jet target was developed for the MAGIX experiment at the high-intensity electron accelerator MESA. It will be operated as an internal, windowless target in the ...energy-recovering recirculation arc of the accelerator with different target gases, e.g., hydrogen, deuterium, helium, oxygen, argon, or xenon. Detailed studies have been carried out at the existing A1 multi-spectrometer facility at the electron accelerator MAMI. This paper focuses on the developed handling procedures and diagnostic tools, and on the performance of the gas jet target under beam conditions. Considering the special features of this type of target, it proves to be well suited for a new generation of high-precision electron scattering experiments at high-intensity electron accelerators.
Polarization transfer to a bound proton in polarized electron knock-out reactions, A(e→,e′p→), is a powerful tool to look for an in-medium modification of the bound proton. It requires comparison to ...calculations that consider the many-body effects accompanying the quasi-free process. We report here measured components Px′, Pz′, and their ratio Px′/Pz′, of polarization transfer to protons bound in Ca40, which is described well by the shell model and for which reliable calculations are available. While the calculations capture the essence of the data, our statistical precision allows us to observe deviations that cannot be explained by simple scaling, including by varying the proton electromagnetic form factor ratio GE/GM. We further explore the deviations of the ratio of the polarization transfer components from that of a free proton, (Px′/Pz′)A/(Px′/Pz′)H, and its dependence on the bound-proton virtuality.