Cryoglobulins: Identification, classification, and novel biomarkers of mysterious proteins

Napodano, Cecilia; Gulli, Francesca; Rapaccini, Gian Ludovico; Marino, Mariapaola; Basile, Umberto

doi:10.1016/bs.acc.2020.09.006

Cited by 23 publications

(18 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…17 Specific amino acid sequences of the IgG cryoglobulins undergo a structural change and auto-aggregate at the level of the quaternary structure of the protein due to a combination of weak non-ionic and hydrophobic interactions culminating in its precipitation. 18 The cryocrit, a measure of centrifuged volume of the precipitate as a percentage of the original serum volume at 4 °C is a prominent laboratory hallmark of cryoglobulinemia, with a cryocrit close to zero considered normal. A cryocrit of 0.5–1% or a direct cryoglobulin concentration over 50mcg/ml is considered diagnostic for cryoglobulinemia.…”

Section: Discussionmentioning

confidence: 99%

Light Chain Myeloma precipitating Cryoglobulinemic Vasculitis

Saeed¹,

Omar²,

Jones³

et al. 2023

Journal of Community Hospital Internal Medicine Perspectives

View full text Add to dashboard Cite

Multiple Myeloma (MM) is characterized by monoclonal immunoglobulin production leading to widespread skeletal destruction and renal dysfunction. Light chain multiple myeloma (LCMM) affects 15% of individuals with MM and has an overall poor prognosis. Cutaneous manifestations are uncommon and it is rarely complicated by Type I Cryoglobulinemia (CG). Here we present an atypical case of κ-predominant LCMM complicated by Type I CG in an 80-year-old man who presented with a progressive non-blanching necrotic rash and ulcers involving his face, distal extremities, and oropharynx of two months duration prior to his admission at our facility. On admission to our facility, workup showed an overabundance of κ-light chains, elevated free κ/λ ratio, cryoglobulins, and an acute kidney injury. Marrow biopsy demonstrated 60% plasma cells with κ-light chain predominance. Cutaneous manifestations such as acral cyanosis and distal gangrene in LCMM indicate late stages of the disease, and such findings should raise suspicion for additional comorbid pathologies, including cryoglobulinemia, which could help direct earlier initiation of treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Light Chain Myeloma precipitating Cryoglobulinemic Vasculitis

Saeed¹,

Omar²,

Jones³

et al. 2023

Journal of Community Hospital Internal Medicine Perspectives

View full text Add to dashboard Cite

show abstract

“…The phenomenon of precipitation is the result of a change in the balance between favorable/unfavorable interactions between CG and solvents at low temperatures. Altered glycosylation may be involved; immune stimulation may perhaps induce circulating desialylated immunoglobulins produced by B lymphocytes [56].…”

Section: Thrombogenic Properties Of the M-protein Predisposing To Art...mentioning

confidence: 99%

Monoclonal Gammopathy of Thrombotic Significance

Gkalea

Fotiou

Dimopoulos

et al. 2023

Cancers

View full text Add to dashboard Cite

The current review provides an overview of the thrombotic risk observed in patients with MG who do not otherwise require treatment. We discuss clinical and biomarker studies that highlight the heterogenous hemostatic profile observed in these patients and how knowledge has evolved over the past 20 years. Biomarker studies suggest shared biologic features between multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS), which involves both hypercoagulability and platelet activation. Hemostatic abnormalities identified in MGUS patients cannot be translated into clinical practice as they lack correlation to clinical events. The prothrombotic phenotype of MGUS patients has not been ascertained yet, but novel data on coagulation markers are promising. We also review rare conditions associated with the thrombogenic properties of the monoclonal protein that predispose to arterial, venous or microthrombotic events and demonstrate that the M-protein can be linked to clinically significant thrombotic events. Cryoglobulinemia, cryofibrinogenemia, cryo-crystaloglobulinemia and MG-related antiphospholipid syndrome are reviewed. We propose the new umbrella term “monoclonal gammopathy of thrombotic significance” (MGTS) to refer to significant, recurrent thrombotic events in patients with MGUS that provide a rationale for targeting the underlying plasma cell clone. Identifying MGUS patients at high risk for thrombotic events is currently a challenge.

show abstract

“…The presence of antiphospholipid antibodies (e.g., in antiphospholipid antibody syndrome or its presence as secondary antiphospholipid in other connective tissue diseases) indicates a major risk for development of vascular thrombosis and cardiovascular diseases [ 53 ]. Cryoglobulin, immunoglobulins that precipitate in vitro at lower temperatures, was shown to be associated with many autoimmune diseases, especially Sjögren’s syndrome, systemic lupus, and hepatitis C viral infection [ 54 ]. Its presence in the blood does not indicate the presence of disease, but it can cause many vascular symptoms due to its precipitation and obstruction of blood vessels of multiple organs ranging from critical vascular ischemia to autoimmune vasculitis [ 55 ], which aggravate endothelial dysfunction [ 56 ].…”

Section: The Effect Of Airds On Vascular Function (Premature Atherosclerosis)mentioning

confidence: 99%

Autoimmune Rheumatic Diseases and Vascular Function: The Concept of Autoimmune Atherosclerosis

Hedar

Stradner

Roessler

et al. 2021

JCM

View full text Add to dashboard Cite

Autoimmune rheumatic diseases (AIRDs) with unknown etiology are increasing in incidence and prevalence. Up to 5% of the population is affected. AIRDs include rheumatoid arthritis, system lupus erythematosus, systemic sclerosis, and Sjögren’s syndrome. In patients with autoimmune diseases, the immune system attacks structures of its own body, leading to widespread tissue and organ damage, which, in turn, is associated with increased morbidity and mortality. One third of the mortality associated with autoimmune diseases is due to cardiovascular diseases. Atherosclerosis is considered the main underlying cause of cardiovascular diseases. Currently, because of finding macrophages and lymphocytes at the atheroma, atherosclerosis is considered a chronic immune-inflammatory disease. In active inflammation, the liberation of inflammatory mediators such as tumor necrotic factor alpha (TNFa), interleukine-6 (IL-6), IL-1 and other factors like T and B cells, play a major role in the atheroma formation. In addition, antioxidized, low-density lipoprotein (LDL) antibodies, antinuclear antibodies (ANA), and rheumatoid factor (RF) are higher in the atherosclerotic patients. Traditional risk factors like gender, age, hypercholesterolemia, smoking, diabetes mellitus, and hypertension, however, do not alone explain the risk of atherosclerosis present in autoimmune diseases. This review examines the role of chronic inflammation in the etiology—and progression—of atherosclerosis in autoimmune rheumatic diseases. In addition, discussed here in detail are the possible effects of autoimmune rheumatic diseases that can affect vascular function. We present here the current findings from studies that assessed vascular function changes using state-of-the-art techniques and innovative endothelial function biomarkers.

show abstract

Cryoglobulins: Identification, classification, and novel biomarkers of mysterious proteins

Cited by 23 publications

References 114 publications

Light Chain Myeloma precipitating Cryoglobulinemic Vasculitis

Light Chain Myeloma precipitating Cryoglobulinemic Vasculitis

Monoclonal Gammopathy of Thrombotic Significance

Autoimmune Rheumatic Diseases and Vascular Function: The Concept of Autoimmune Atherosclerosis

Contact Info

Product

Resources

About