Crystal-storing histiocytosis with renal Fanconi syndrome: pathological and molecular characteristics compared with classical myeloma-associated Fanconi syndrome

Hamel, Chahrazed El; Thierry, Antoine; Trouillas, Patrick; Bridoux, Frank; Carrion, Claire; Quellard, Nathalie; Goujon, Jean-Michel; Aldigier, Jean-Claude; Gombert, Jean‐Marc; Cogné, Michel; Touchard, Guy

doi:10.1093/ndt/gfq129

Cited by 74 publications

(60 citation statements)

References 39 publications

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“…In addition, CSH can involve various tissues, including spleen and lymph nodes, sometimes in the context of systemic symptoms with macrophage activation. [101][102] Very few series of LC-associated FS have been published, and the efficacy of the so-called novel anti-myeloma agents has not been evaluated. In most cases, FS appears to slowly progress toward ESRD and rarely symptomatic myeloma.…”

Section: Acquired Fsmentioning

confidence: 99%

How I treat monoclonal gammopathy of renal significance (MGRS)

Fermand¹,

Bridoux²,

Kyle

et al. 2013

Blood

269

220

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Recently, the term monoclonal gammopathy of renal significance (MGRS) was introduced to distinguish monoclonal gammopathies that result in the development of kidney disease from those that are benign. By definition, patients with MGRS have B-cell clones that do not meet the definition of multiple myeloma or lymphoma. Nevertheless, these clones produce monoclonal proteins that are capable of injuring the kidney resulting in permanent damage. Except for immunoglobulin light chain amyloidosis with heart involvement in which death can be rapid, treatment of MGRS is often indicated more to preserve kidney function and prevent recurrence after kidney transplantation rather than the prolongation of life. Clinical trials are rare for MGRS-related kidney diseases, except in immunoglobulin light chain amyloidosis. Treatment recommendations are therefore based on the clinical data obtained from treatment of the clonal disorder in its malignant state. The establishment of these treatment recommendations is important until data can be obtained by clinical trials of MGRS-related kidney diseases.

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Section: Acquired Fsmentioning

confidence: 99%

How I treat monoclonal gammopathy of renal significance (MGRS)

Fermand¹,

Bridoux²,

Kyle

et al. 2013

Blood

269

220

View full text Add to dashboard Cite

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“…Although CSH appears to develop in patients with plasma cell tumors expressing any HC classes, the involved LCs are almost always the κ isotype [111] and have the highest homology with V κ 1 variability subgroup, germline gene O8/O18 [124, 125]. It is not yet fully clear whether the preexisting Ig crystals in the extracellular space were phagocytosed by macrophages and were retained in the endosomal organelles or whether the culprit Ig clones accumulated in the endocytic organelles before crystal nucleation took place de novo in this acidic compartment.…”

Section: Crystalline Body Biogenesis: Mechanisms Of Intracellular mentioning

confidence: 99%

Aggregates, Crystals, Gels, and Amyloids: Intracellular and Extracellular Phenotypes at the Crossroads of Immunoglobulin Physicochemical Property and Cell Physiology

Hasegawa

2013

International Journal of Cell Biology

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Recombinant immunoglobulins comprise an important class of human therapeutics. Although specific immunoglobulins can be purposefully raised against desired antigen targets by various methods, identifying an immunoglobulin clone that simultaneously possesses potent therapeutic activities and desirable manufacturing-related attributes often turns out to be challenging. The variable domains of individual immunoglobulins primarily define the unique antigen specificities and binding affinities inherent to each clone. The primary sequence of the variable domains also specifies the unique physicochemical properties that modulate various aspects of individual immunoglobulin life cycle, starting from the biosynthetic steps in the endoplasmic reticulum, secretory pathway trafficking, secretion, and the fate in the extracellular space and in the endosome-lysosome system. Because of the diverse repertoire of immunoglobulin physicochemical properties, some immunoglobulin clones' intrinsic properties may manifest as intriguing cellular phenotypes, unusual solution behaviors, and serious pathologic outcomes that are of scientific and clinical importance. To gain renewed insights into identifying manufacturable therapeutic antibodies, this paper catalogs important intracellular and extracellular phenotypes induced by various subsets of immunoglobulin clones occupying different niches of diverse physicochemical repertoire space. Both intrinsic and extrinsic factors that make certain immunoglobulin clones desirable or undesirable for large-scale manufacturing and therapeutic use are summarized.

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“…These morphological differences were associated with distinct molecular structure peculiarities of the κ-LC variable domains, but led to the same typical resistance of the V domain to trypsin digestion. Comparison of the 3D-structures of the CSH/FS Vκ1 and Vκ3 domains with the germline-encoded structures and those from patients with myeloma-associated FS revealed distinct hydrophobic residues exposed to the solvent, likely favoring the formation of a variant form of crystals that may further resist degradation after phagocytosis [80].…”

Section: Monoclonal Lc-associated Fs: An Overviewmentioning

confidence: 99%

Toward Understanding Renal Fanconi Syndrome: Step by Step Advances through Experimental Models

Sirac

Bridoux

Essig

et al. 2011

Contributions to Nephrology

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Renal Fanconi syndrome (FS) is a generalized dysfunction of proximal tubular epithelial cells leading to the urinary leak of essential metabolites like phosphate, uric acid, glucose, amino acids and low molecular weight proteins. From inherited forms involving mutations on apparently unrelated genes to acquired forms induced by drugs, heavy metals or monoclonal immunoglobulin (Ig) light chains (LC), heterogeneous causalities of FS have complicated the understanding of this pathology for a long time. Experimental models of FS have allowed researchers to face the challenge and have helped unravel the main mechanisms disturbing proximal tubule reabsorption. Administration of cadmium to animals first demonstrated an inhibition of Na/K/ATPase activity, highlighting how a single toxic component could induce the general sodium-linked transport defect observed in FS. Today, genetically modified mice allow the development of reliable and reproducible experimental models for inherited or acquired forms of FS. One of the most exciting advances offered by these models is the unexpected major role of endocytosis in the function of the proximal tubule revealed by megalin and ClC-5 knockout mice. Using gene-targeted insertion, a transgenic mouse for LC-associated FS, the most frequent adult form of FS, has also been recently developed and represents a major step in the development of models of this pathology. Beyond deciphering molecular and cellular events at the origin of FS, these models also represent essential tools for the development of therapeutic strategies.

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Crystal-storing histiocytosis with renal Fanconi syndrome: pathological and molecular characteristics compared with classical myeloma-associated Fanconi syndrome

Cited by 74 publications

References 39 publications

How I treat monoclonal gammopathy of renal significance (MGRS)

How I treat monoclonal gammopathy of renal significance (MGRS)

Aggregates, Crystals, Gels, and Amyloids: Intracellular and Extracellular Phenotypes at the Crossroads of Immunoglobulin Physicochemical Property and Cell Physiology

Toward Understanding Renal Fanconi Syndrome: Step by Step Advances through Experimental Models

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