Pathological crystallization of human immunoglobulins
Ying Wang,Aleksey Lomakin,Teru Hideshima,Jacob P. Laubach,Olutayo Ogun,Paul G. Richardson,Nikhil C. Munshi,Kenneth C. Anderson,George B. Benedek +8 more
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TLDR
A study of monoclonal IgG cryoglobulins overexpressed by two patients with multiple myeloma suggests that, even within the regular immune response to infections, cryoprecipitation of Ig can be possible.Abstract:
Condensation of Igs has been observed in pharmaceutical formulations and in vivo in cases of cryoglobulinemia. We report a study of monoclonal IgG cryoglobulins overexpressed by two patients with multiple myeloma. These cryoglobulins form crystals, and we measured their solubility lines. Depending on the supersaturation, we observed a variety of condensate morphologies consistent with those reported in clinical investigations. Remarkably, the crystallization can occur at quite low concentrations. This suggests that, even within the regular immune response to infections, cryoprecipitation of Ig can be possible.read more
Citations
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How I treat cryoglobulinemia
TL;DR: The spectrum of this heterogeneous disease is explored by discussing the disease characteristics of 5 different patients by discussing how cryoglobulinemia affects clinical presentation, treatment, and underlying cause vary.
Journal ArticleDOI
Phase transitions in human IgG solutions
Ying Wang,Aleksey Lomakin,Ramil F. Latypov,Jacob P. Laubach,Teru Hideshima,Paul G. Richardson,Nikhil C. Munshi,Kenneth C. Anderson,George B. Benedek +8 more
TL;DR: An experimental approach to study IgG solutions in which the phase transitions are hidden below the freezing point of the solution, which provides a foundation for further experimental and theoretical studies of the phase behavior of generic IgGs as well as outliers with large propensity to condense.
Journal ArticleDOI
The Materials Science of Pathological Crystals
Laura N. Poloni,Michael D. Ward +1 more
TL;DR: In this paper, real-time in situ atomic force microscopy (AFM) has been used to elucidate the effect of urinary substituents on calcium-containing crystals that aggregate to form kidney stones, demonstrating the role of anionic proteins, synthetic polymers and small molecules on crystal growth regulation.
Journal ArticleDOI
Cryoglobulins: An update on detection, mechanisms and clinical contribution.
TL;DR: A protocol for detection and identification of cryoglobulins lack standardization, and a protocol for such detection, characterization and quantification is proposed.
Journal ArticleDOI
Kinetics of liquid–liquid phase separation in protein solutions exhibiting LCST phase behavior studied by time-resolved USAXS and VSANS
Stefano Da Vela,Michal K. Braun,Andreas Dörr,Alessandro Greco,Johannes Möller,Zhendong Fu,Fajun Zhang,Frank Schreiber +7 more
TL;DR: The kinetics of the liquid-liquid phase separation and its arrest in protein solutions exhibiting a lower critical solution temperature (LCST) phase behavior using the combination of ultra-small angle X-ray scattering (USAXS) and very- small angle neutron scattering (VSANS) are studied.
References
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TL;DR: Baseline myeloma-associated neuropathy seems more common than previously reported, and bortezomib- associated neuropathy, although a common toxicity, is reversible in most patients.
Journal ArticleDOI
Crystal cataracts: Human genetic cataract caused by protein crystallization
Ajay Pande,Jayanti Pande,Neer Asherie,Aleksey Lomakin,Olutayo Ogun,Jonathan King,George B. Benedek +6 more
TL;DR: A molecular basis for lens opacity in two genetic cataracts is provided and it is suggested that the opacity occurs because of the spontaneous crystallization of the mutant proteins.
Journal ArticleDOI
Structure of human IgM rheumatoid factor Fab bound to its autoantigen IgG Fc reveals a novel topology of antibody-antigen interaction.
A.L. Corper,Maninder K. Sohi,Vincent R. Bonagura,Michael Steinitz,Royston Jefferis,Arnold Feinstein,Dennis Beale,Michael J. Taussig,Brian J. Sutton +8 more
TL;DR: The crystal structure of the Fab fragment of a patient-derived IgM rheumatoid factor complexed with human lgG4 Fc, at 3.2 Å resolution, is reported, which is the first structure of an autoantibody–autoantigen complex.
Journal ArticleDOI
Aeolotopic interactions of globular proteins
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