IgG cryoglobulinemia

OBJECTIVE: Mixed Cryoglobulinemia is the most well-known Hepatitis C Virus (HCV)-associated extrahepatic manifestation. MC is both an autoimmune and B-lymphoproliferative disorder. Cryoglobulins (CGs) are classified into three groups according to immunoglobulin (Ig) composition: type I is composed of one isotype or Ig class. Type II and type III mixed CGs are immune complexes composed of polyclonal IgGs acting as autoantigens and mono, polyclonal or oligoclonal IgM with rheumatoid factor activity. IgG1 and IgG3 are the predominant subclasses involved. This study shows the simultaneous presence of IgG-RF and IgG3, supporting the hypothesis of an involvement of this subclass in the initiation of early stages of CGs. PATIENTS AND METHODS: We describe a case series of six HCV-positive patients, all of whom had peripheral neuropathy and transient ischemic attacks, presenting cryoprecipitates formed by IgG3 and IgG1. Cryoprecipitate IgG subclass research was carried out by immunofixation electrophoresis by using antisera against IgG1, IgG2, IgG3, and IgG4. RESULTS: Our six patients presented with an immunochemical pattern characterized by the mere presence of IgG1 and IgG3 subclasses with probable RF activity and one of these six patients exhibited monoclonal IgG3 in his cerebrospinal fluid. CONCLUSIONS: We can hypothesize that the IgG passage through the blood-brain barrier could have contributed to the cause of TIAs, through a mechanism involving the precipitation of circulating immune complexes formed by the two subclasses in the intrathecal vessels

NLRP3 Inflammasome Involvement in Heart, Liver, and Lung Diseases—A Lesson from Cytokine Storm Syndrome

Inflammation and inflammasomes have been proposed as important regulators of the host-microorganism interaction, playing a key role in morbidity and mortality due to the coronavirus disease 2019 (COVID-19) in subjects with chronic conditions and compromised immune system. The inflammasome consists of a multiprotein complex that finely regulates the activation of caspase-1 and the production and secretion of potent pro-inflammatory cytokines such as IL-1 beta and IL-18. The pyrin containing NOD (nucleotide-binding oligomerization domain) like receptor (NLRP) is a family of intracellular receptors, sensing patterns associated to pathogens or danger signals and NLRP3 inflammasome is the most deeply analyzed for its involvement in the innate and adaptive immune system as well as its contribution to several autoinflammatory and autoimmune diseases. It is highly expressed in leukocytes and up-regulated in sentinel cells upon inflammatory stimuli. NLRP3 expression has also been reported in B and T lymphocytes, in epithelial cells of oral and genital mucosa, in specific parenchymal cells as cardiomyocytes, and keratinocytes, and chondrocytes. It is well known that a dysregulated activation of the inflammasome is involved in the pathogenesis of different disorders that share the common red line of inflammation in their pathogenetic fingerprint. Here, we review the potential roles of the NLRP3 inflammasome in cardiovascular events, liver damage, pulmonary diseases, and in that wide range of systemic inflammatory syndromes named as a cytokine storm

Serum free light chain quantitative assays: Dilemma of a biomarker

Background: Serum free light chains detection assays are consistently meeting greater interest for the diagnosis and monitoring of monoclonal gammopathies and plasma cell dyscrasias. Nowadays, there are neither standardized methods nor reference material for the determination of free light chains; for this reason, it is important to compare two different assays used in clinical laboratory. Methods: We evaluated 300 serum samples from patients with B-cell disorders and compared the analytical performances of both assay. Each test was assayed on both testing platforms (Siemens Dade Behring BN II Nephelometer and SPAPLUS by The Binding Site). κ/λ ratios were determined and compared. Results were analyzed by Passing-Bablok and Bland-Altman plots to evaluate comparability of the two techniques and to determine bias. Results: The reproducibility of both assays is acceptable, reaching minimum and desirable analytical goals derived from biological variability. However, values are not interchangeable between systems. This study shows that the two systems do not allow results to be transferred from one method to the other even if they display good agreement. Conclusion: Our study highlights the importance of elaborating an international standard for free light chains quantification in order to offer homogeneous results as well as guarantee harmonization of values among laboratories. Moreover, the assays should be validated in specific patient groups to determine that they are clinically fit for purpose

The PAU Survey & Euclid: Improving broad-band photometric redshifts with multi-task learning

Current and future imaging surveys require photometric redshifts (photo-z) to be estimated for millions of galaxies. Improving the photo-z quality is a major challenge to advance our understanding of cosmology. In this paper, we explore how the synergies between narrow-band photometric data and large imaging surveys can be exploited to improve broad-band photometric redshifts. We use a multi-task learning (MTL) network to improve broad-band photo-z estimates by simultaneously predicting the broad-band photo-z and the narrow-band photometry from the broad-band photometry. The narrow-band photometry is only required in the training field, which enables better photo-z predictions also for the galaxies without narrow-band photometry in the wide field. This technique is tested with data from the Physics of the Accelerating Universe Survey (PAUS) in the COSMOS field. We find that the method predicts photo-z that are 14% more precise down to magnitude i_AB<23, while reducing the outlier rate by 40% with respect to the baseline network mapping broad-band colours to only photo-zs. Furthermore, MTL significantly reduces the photo-z bias for high-redshift galaxies, improving the redshift distributions for tomographic bins with z>1. Applying this technique to deeper samples is crucial for future surveys like \Euclid or LSST. For simulated data, training on a sample with i_AB <23, the method reduces the photo-z scatter by 15% for all galaxies with 24<i_AB<25. We also study the effects of extending the training sample with photometric galaxies using PAUS high-precision photo-zs, which further reduces the photo-z scatter.Comment: 20 pages, 16 figure

Euclid preparation: XII. Optimizing the photometric sample of the Euclid survey for galaxy clustering and galaxy-galaxy lensing analyses

Photometric redshifts (photo-zs) are one of the main ingredients in the analysis of cosmological probes. Their accuracy particularly affects the results of the analyses of galaxy clustering with photometrically selected galaxies (GCph) and weak lensing. In the next decade, space missions such as Euclid will collect precise and accurate photometric measurements for millions of galaxies. These data should be complemented with upcoming ground-based observations to derive precise and accurate photo-zs. In this article we explore how the tomographic redshift binning and depth of ground-based observations will affect the cosmological constraints expected from the Euclid mission. We focus on GCph and extend the study to include galaxy-galaxy lensing (GGL). We add a layer of complexity to the analysis by simulating several realistic photo-z distributions based on the Euclid Consortium Flagship simulation and using a machine learning photo-z algorithm. We then use the Fisher matrix formalism together with these galaxy samples to study the cosmological constraining power as a function of redshift binning, survey depth, and photo-z accuracy. We find that bins with an equal width in redshift provide a higher figure of merit (FoM) than equipopulated bins and that increasing the number of redshift bins from ten to 13 improves the FoM by 35% and 15% for GCph and its combination with GGL, respectively. For GCph, an increase in the survey depth provides a higher FoM. However, when we include faint galaxies beyond the limit of the spectroscopic training data, the resulting FoM decreases because of the spurious photo-zs. When combining GCph and GGL, the number density of the sample, which is set by the survey depth, is the main factor driving the variations in the FoM. Adding galaxies at faint magnitudes and high redshift increases the FoM, even when they are beyond the spectroscopic limit, since the number density increase compensates for the photo-z degradation in this case. We conclude that there is more information that can be extracted beyond the nominal ten tomographic redshift bins of Euclid and that we should be cautious when adding faint galaxies into our sample since they can degrade the cosmological constraints

Euclid preparation: XII. Optimizing the photometric sample of the Euclid survey for galaxy clustering and galaxy-galaxy lensing analyses

Photometric redshifts (photo-zs) are one of the main ingredients in the analysis of cosmological probes. Their accuracy particularly affects the results of the analyses of galaxy clustering with photometrically selected galaxies (GCph) and weak lensing. In the next decade, space missions such as Euclid will collect precise and accurate photometric measurements for millions of galaxies. These data should be complemented with upcoming ground-based observations to derive precise and accurate photo-zs. In this article we explore how the tomographic redshift binning and depth of ground-based observations will affect the cosmological constraints expected from the Euclid mission. We focus on GCph and extend the study to include galaxy-galaxy lensing (GGL). We add a layer of complexity to the analysis by simulating several realistic photo-z distributions based on the Euclid Consortium Flagship simulation and using a machine learning photo-z algorithm. We then use the Fisher matrix formalism together with these galaxy samples to study the cosmological constraining power as a function of redshift binning, survey depth, and photo-z accuracy. We find that bins with an equal width in redshift provide a higher figure of merit (FoM) than equipopulated bins and that increasing the number of redshift bins from ten to 13 improves the FoM by 35% and 15% for GCph and its combination with GGL, respectively. For GCph, an increase in the survey depth provides a higher FoM. However, when we include faint galaxies beyond the limit of the spectroscopic training data, the resulting FoM decreases because of the spurious photo-zs. When combining GCph and GGL, the number density of the sample, which is set by the survey depth, is the main factor driving the variations in the FoM. Adding galaxies at faint magnitudes and high redshift increases the FoM, even when they are beyond the spectroscopic limit, since the number density increase compensates for the photo-z degradation in this case. We conclude that there is more information that can be extracted beyond the nominal ten tomographic redshift bins of Euclid and that we should be cautious when adding faint galaxies into our sample since they can degrade the cosmological constraints

Euclid preparation: VIII. The Complete Calibration of the Colour–Redshift Relation survey: VLT/KMOS observations and data release

The Complete Calibration of the Colour–Redshift Relation survey (C3R2) is a spectroscopic effort involving ESO and Keck facilities designed specifically to empirically calibrate the galaxy colour–redshift relation – P(z|C) to the Euclid depth (iAB = 24.5) and is intimately linked to the success of upcoming Stage IV dark energy missions based on weak lensing cosmology. The aim is to build a spectroscopic calibration sample that is as representative as possible of the galaxies of the Euclid weak lensing sample. In order to minimise the number of spectroscopic observations necessary to fill the gaps in current knowledge of the P(z|C), self-organising map (SOM) representations of the galaxy colour space have been constructed. Here we present the first results of an ESO@VLT Large Programme approved in the context of C3R2, which makes use of the two VLT optical and near-infrared multi-object spectrographs, FORS2 and KMOS. This data release paper focuses on high-quality spectroscopic redshifts of high-redshift galaxies observed with the KMOS spectrograph in the near-infrared H- and K-bands. A total of 424 highly-reliable redshifts are measured in the 1.3 ≤ z ≤ 2.5 range, with total success rates of 60.7% in the H-band and 32.8% in the K-band. The newly determined redshifts fill 55% of high (mainly regions with no spectroscopic measurements) and 35% of lower (regions with low-resolution/low-quality spectroscopic measurements) priority empty SOM grid cells. We measured Hα fluxes in a 1. 002 radius aperture from the spectra of the spectroscopically confirmed galaxies and converted them into star formation rates. In addition, we performed an SED fitting analysis on the same sample in order to derive stellar masses, E(B − V), total magnitudes, and SFRs. We combine the results obtained from the spectra with those derived via SED fitting, and we show that the spectroscopic failures come from either weakly star-forming galaxies (at z 2 galaxies

Free light chains: Eclectic multipurpose biomarker

he production of antibodies is accompanied by a slight excess of synthesis of kappa and lambda, immunoglobulin light chains; small amounts of them are released in the peripheral blood and can also be found in various body fluids, such as synovial fluid, cerebrospinal fluid, urine and saliva. They are rapidly filtered by the glomerulus and &gt; 99% are reabsorbed from the cells of the proximal convoluted tubule, making them present in the urine in only trace amounts. The production of an excess of protein without a reason or a specific function in a biological system is rare. Free light chains, considered for years a waste product of Ig synthesis, are currently known to be very active molecules, able to bind antigens as well as whole immunoglobulin and helping to develop specific antibody affinity. The ability of free light chains to activate mast cells and then become an active part of the pathogenic mechanisms of chronic inflammatory diseases has increased interest in their clinical use, both as an attractive therapeutic target or as a biochemical marker of disease evolution or remission. This is an overview of relevant scientific interest that immunoglobulin light chains kappa and lambda. have attracted over the years, a report on the progress in knowledge about their structure and function, with a special focus on their biological meaning and potential clinical utility in different diseases