Glycoproteomic analysis of abnormal N-glycosylation on the kappa chain of cryocrystalglobulin in a patient of multiple myeloma

Toda, Tosifusa; Nakamura, Megumi; Yamada, Masaki; Nishine, Tsutomu; Torii, Tomohiro; Ikenaka, Kazuhiro; Mori, Mayumi

doi:10.2198/jelectroph.53.1

Cited by 8 publications

(3 citation statements)

References 12 publications

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“…However, similar to our study, they also noted higher variation in sialylation level among patients with active myeloma when compared to healthy control. Sialylated glycans located on the IgG light chain and an increase in its molecular weight in SDS-PAGE have been previously reported in multiple myeloma and associated with spontaneous precipitation . We found heavier light chains in patients MM1, MM2, MM5, REL3, MGUS4, and MGUS6 with all samples but MM2 being of the lambda subtype.…”

Section: Discussionsupporting

confidence: 69%

Polyclonal Immunoglobulin G N-Glycosylation in the Pathogenesis of Plasma Cell Disorders

et al. 2016

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The pathological progression from benign monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM) and finally to active myeloma (MM) is poorly understood. Abnormal immunoglobulin G (IgG) glycosylation in myeloma has been reported. Using a glycomic platform composed of hydrophilic interaction UPLC, exoglycosidase digestions, weak anion-exchange chromatography, and mass spectrometry, polyclonal IgG N-glycosylation profiles from 35 patients [MGUS (n = 8), SMM (n = 5), MM (n = 8), complete-response (CR) post-treatment (n = 5), relapse (n = 4), healthy age-matched control (n = 5)] were characterized to map glycan structures in distinct disease phases of multiple myeloma. N-Glycan profiles from MGUS resembled normal control. The abundance of neutral glycans containing terminal galactose was highest in SMM, while agalactosylated glycans and fucosylated glycans were lowest in MM. Three afucosyl-biantennary-digalactosylated-sialylated species (A2G2S1, A2BG2S1, and A2BG2S2) decreased 2.38-, 2.4-, and 4.25-fold, respectively, from benign to active myeloma. Increased light chain sialylation was observed in a longitudinal case of transformation from MGUS to MM. Bisecting N-acetylglucosamine was lowest in the CR group, while highest in relapsed disease. Gene expression levels of FUT 8, ST6GAL1, B4GALT1, RECK, and BACH2 identified from publicly available GEP data supported the glycomic changes seen in MM compared to control. The observed differential glycosylation underlined the heterogeneity of the myeloma spectrum. This study demonstrates the feasibility of mapping glycan modifications on the IgG molecule and provides proof of principle that differential IgG glycosylation patterns can be successfully identified in plasma cell disorders.

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Section: Discussionsupporting

confidence: 69%

Polyclonal Immunoglobulin G N-Glycosylation in the Pathogenesis of Plasma Cell Disorders

et al. 2016

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“…Nonfucosylated oligosaccharides on the κ chain of crystalglobulins, which lead to protein misfolding and insolubility of immunoglobulin, have been suggested. [ 9 , 10 ] In cases of crystalglobulinemia, despite negative findings of cryoglobulins and cryofibrinogens according to routine laboratory studies, cryoprecipitates can be observed grossly in blood collection tubes or microscopically in blood smears. Microscopic detection of irreversible cryoprecipitation and the presence of intravascular crystalized bodies in affected tissues in pathological specimens are critical for the diagnosis of crystalglobulinemia.…”

Section: Discussionmentioning

confidence: 99%

Crystalglobulinemia manifesting as chronic arthralgia and acute limb ischemia

Abe

Tomita²,

Bohgaki³

et al. 2017

Medicine

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Rationale:Crystalglobulinemia is a rare disease caused by monoclonal immunoglobulins, characterized by irreversible crystallization on refrigeration. It causes systemic symptoms including purpura, arthralgia, and vessel occlusive conditions to be exacerbated by exposure to cold. We report a patient with crystalglobulinemia associated with monoclonal gammopathy of undetermined significance (MGUS) manifesting as chronic arthralgia and recurrent acute arterial occlusion.Presenting concerns:A 61-year-old man, who had been diagnosed with MGUS and who had arthralgia of unknown origin, presented with recurrent acute limb ischemia after surgical thromboembolectomy. Refrigeration of his serum formed precipitates that looked like needle-shaped crystals. These crystals did not dissolve with warming, which is not a characteristic of cryoglobulins. Skin biopsy results showed crystal-liked eosinophilic bodies in small vessels and we diagnosed crystalglobulinemia.Intervention and outcomes:Although he underwent above-knee amputation, he was treated with a bortezomib and dexamethasone-based chemotherapeutic regimen, following lenalidomide maintenance therapy. Finally, he achieved complete remission and serum crystalglobulins diminished.Lessons:Monoclonal gammopathy, previously diagnosed as MGUS, can cause systemic symptoms and thrombotic conditions by producing pathologic immunoglobulins, such as crystalglobulins. In such situations, MGUS, even when it has not progressed to multiple myeloma, can be a target of aggressive chemotherapy. Crystalglobulinemia should be considered for patients with monoclonal gammopathy manifesting as systemic and thrombotic symptoms exacerbated by cooling.

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“…In addition, cylinder-like bodies were found in deep organs that are not affected by external temperature. It has been reported that glycosylation of an N-terminal residue of the immunoglobulin light chain is related to crystallization (11,19).…”

Section: Discussionmentioning

confidence: 99%

Crystalglobulinemia with Fulminant Course with Cylinder-like Bodies on Peripheral Blood Smear

et al. 2014

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A 63-year-old woman presented to our hospital with fever, purpura and pain in both legs and died 4 days after admission. Her blood smear and skin biopsy showed cylinder-like bodies (20×120 μm). She was diagnosed to have monoclonal gammopathy (IgG, lambda type). An autopsy revealed cylinder-like bodies in the vasculature of various organs. We noted a proliferation of atypical plasma cells in her bone marrow, suggesting pre-existing myeloma. Crystalglobulinemia is a rare manifestation of hypergammaglobulinemia that can cause multiple embolisms of the small vessels, and this resulted in the patient's fulminant course. The identification of cylinder-like bodies in the peripheral blood may help in reaching a diagnosis in such cases.

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Glycoproteomic analysis of abnormal N-glycosylation on the kappa chain of cryocrystalglobulin in a patient of multiple myeloma

Cited by 8 publications

References 12 publications

Polyclonal Immunoglobulin G N-Glycosylation in the Pathogenesis of Plasma Cell Disorders

Polyclonal Immunoglobulin G N-Glycosylation in the Pathogenesis of Plasma Cell Disorders

Crystalglobulinemia manifesting as chronic arthralgia and acute limb ischemia

Crystalglobulinemia with Fulminant Course with Cylinder-like Bodies on Peripheral Blood Smear

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