Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins

Background Immunoglobulin A nephritis (IgAN) is the most common primary glomerulonephritis worldwide. It is caused by accumulation of IgA1-containing immune complexes in the kidney resulting in renal failure, which is thought to be due to altered glycosylation of IgA with a decrease of 2-3-sialylated galactosides (NeuAc alpha 2-3Gal). less thanbrgreater than less thanbrgreater thanPurpose The purpose of this study was to analyze whether altered glycosylation of IgA would lead to an altered binding to galectin-8, an endogenous lectin with strong affinity for 2-3-sialylated galactosides. Galectins are a family of beta-galactoside-binding proteins; by binding various glycoproteins, they play important roles in the regulation of cellular functions in inflammation and immunity. Hence, an altered binding of IgA to galectin-8 could lead to pathologic immune functions, such as glomerulonephritis. less thanbrgreater than less thanbrgreater thanMethods Affinity chromatography of serum glycoproteins on the human sialogalactoside-binding lectin galectin-8N permitted quantitation of bound and unbound fractions, including IgA. less thanbrgreater than less thanbrgreater thanResults Analysis of similar to 100 IgA nephritis sera showed that the galectin-8N unbound fraction of IgA increased compared to similar to 100 controls, consistent with the known loss of galactosylation. A subgroup of similar to 15% of the IgAN patients had a ratio of galectin-8 bound/unbound IgA andlt;0.09, not found for any of the controls. Unexpectedly, the galectin-8N-binding fraction of serum glycoproteins other than IgA increased in the sera of IgAN patients but not in controls, suggesting a previously unrecognized change in this disease. less thanbrgreater than less thanbrgreater thanConclusion This is the first study that relates a galectin, an endogenous lectin family, to IgA nephritis and thus should stimulate new avenues of research into the pathophysiology of the disease.Funding Agencies|Swedish Research Council (Vetenskapsradet)|2008-3356|Swedish Foundation for Swedish Research|FFL4|Swedish Healthcare System (ALF)||Region Skane||</p

Structural study of an amorphous NiZr2 alloy by anomalous wide angle X-ray scattering and Reverse Monte Carlo simulations

The local atomic structure of an amorphous NiZr2 alloy was investigated using the anomalous wide-angle x-ray scattering (AWAXS), differential anomalous scattering (DAS) and reverse Monte Carlo (RMC) simulations techniques. The AWAXS measurements were performed at eight different incident photon energies, including some close to the Ni and Zr K edges. From the measurements eight total structure factor S(K,E) were derived. Using the AWAXS data four differential structure factors DSFi(K,Em,En) were derived, two about the Ni and Zr edges. The partial structure factors SNi-Ni(K), SNi-Zr(K) and SZr-Zr(K) were estimated by using two different methods. First, the S(K,E) and DSFi(K,Em,En) factors were combined and used in a matrix inversion process. Second, three S(K,E) factors were used as input data in the RMC technique. The coordination numbers and interatomic distances for the first neighbors extracted from the partial structure factors obtained by these two methods show a good agreement. By using the three-dimensional structure derived from the RMC simulations, the bond-angle distributions were calculated and they suggest the presence of distorted triangular-faced polyhedral units in the amorphous NiZr2 structure. We have used the Warren chemical short-range order parameter to evaluate the chemical short-range order for the amorphous NiZr2 alloy and for the NiZr2 compound. The calculated values show that the chemical short-range order found in these two materials is similar to that found in a solid solution.Comment: Submitted to Phys. Rev. B, 8 figure