Cryoglobulins: An update on detection, mechanisms and clinical contribution

Kolopp‐Sarda, Marie‐Nathalie; Miossec, Pierre

doi:10.1016/j.autrev.2017.11.035

Cited by 51 publications

(104 citation statements)

References 58 publications

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“…Patients who had serum tested for cryoglobulins between January 2010 and December 2016 were included (mean ± SD age 52.4 ± 17.9 years; 8,026 women versus 5,413 men [female:male ratio 1.48]) (n = 13,439). All cryoglobulins were detected and analyzed with previously described techniques . Blood samples were collected in 3–5‐ml tubes with red top and clot activator (BD Vacutainer).…”

Section: Methodsmentioning

confidence: 99%

Cryoglobulins Today: Detection and Immunologic Characteristics of 1,675 Positive Samples From 13,439 Patients Obtained Over Six Years

Kolopp‐Sarda

Nombel

Miossec

2019

Arthritis & Rheumatology

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Objective Cryoglobulins are cold‐precipitating immunoglobulins. Through progress in techniques, we undertook this study to update information on the biologic characteristics of cryoglobulins in a very large population. Methods A cohort of 13,439 patients was tested for cryoglobulins from January 2010 to December 2016. The analysis included cryoglobulin isotype, clonality, concentration, and IgM rheumatoid factor (IgM‐RF) in cryoprecipitate, as well as serum complement and RF. Markers of gammopathy, viral infection, and autoimmunity were also investigated. Results Of the 13,439 patients, 1,675 (12.5%) tested positive for cryoglobulins: 155 patients (9.3%) with type I, 788 (47%) with type II, and 732 (43.7%) with type III cryoglobulins. Nine percent of patients who were retested after initially testing negative for cryoglobulins showed a positive result on a follow‐up test (196 of the 2,213 retested patients). In type I cryoglobulins, IgM was more frequent but occurred at lower concentrations than IgG. Mixed cryoglobulins were found in 34.8% of the tested patients who were positive for hepatitis C virus and <5% of those who were positive for hepatitis B virus or HIV. Of the patients with anti–double‐stranded DNA, anti‐SSA, or anti–cyclic citrullinated peptide autoantibodies, 25.4% tested positive for mixed cryoglobulins, with type III occurring more frequently than type II. Both cryoprecipitate and serum were RF‐positive in 21.6% of type II and 10.1% of type III cryoglobulins. A decrease of C4, with or without accompanying decreases of C3 and CH50, was found in 23.6% of cryoglobulin samples. Conclusion Obtained with the use of modern assays, our findings from this very large collection of cryoglobulins provide an update on cryoglobulin distribution and characteristics, with minimal selection bias. Despite strict preanalytical conditions, a negative finding for the presence of cryoglobulin must be confirmed in a second sample. RF activity and complement decreases were rarely detected.

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Section: Methodsmentioning

confidence: 99%

Cryoglobulins Today: Detection and Immunologic Characteristics of 1,675 Positive Samples From 13,439 Patients Obtained Over Six Years

Kolopp‐Sarda

Nombel

Miossec

2019

Arthritis & Rheumatology

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“…Cryoglobulin concentrations were assessed at DAA initiation, during therapy and after the end of treatment until cryoglobulin clearance if any. Cryoglobulin detection, purification, and characterization were performed in the Immunology Laboratory of the Hospices Civils de Lyon as described in the Appendix (Supporting information) [8].…”

Section: Cryoglobulin Detection and Characterizationmentioning

confidence: 99%

Benefit of direct-acting antiviral therapy for hepatitis C virus (HCV) in monoinfected and HIV-HCV-coinfected patients with mixed cryoglobulinaemia

Miailhes

Hartig‐Lavie

Virlogeux

et al. 2018

Clinical Microbiology and Infection

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“…Cryoglobulins are classified into three types based on the Brouet classification criteria. This system is based on the association with clinical presentations and underlying etiology [7]. Type 1 cryoglobulins are monoclonal immunoglobulins associated with B-cell lineage malignancy; type 2 and 3 are mixed cryoglobulins, often associated with persistent infections including hepatitis B and C virus infections, HIV, lymphoproliferative diseases, and autoimmune diseases such as systemic lupus erythematosus [3,[7][8].…”

Section: Discussionmentioning

confidence: 99%

“…This system is based on the association with clinical presentations and underlying etiology [7]. Type 1 cryoglobulins are monoclonal immunoglobulins associated with B-cell lineage malignancy; type 2 and 3 are mixed cryoglobulins, often associated with persistent infections including hepatitis B and C virus infections, HIV, lymphoproliferative diseases, and autoimmune diseases such as systemic lupus erythematosus [3,[7][8]. Vasculitis occurs due to precipitation of monoclonal immunoglobulins in small-to medium-sized vessels or precipitation of immune complexes in the microcirculation [7].…”

Section: Discussionmentioning

confidence: 99%

“…The classic Meltzer's triad of purpura, arthralgia, and weakness was first described in 1966; its components occur in approximately 90%, 80%, and 50% of patients with CV, respectively [7][8][9]. Renal involvement occurs in approximately 30% of patients, ranging from isolated subnephrotic proteinuria or hematuria to nephritic or nephrotic syndromes to acute or chronic renal failure.…”

Section: Discussionmentioning

confidence: 99%

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Cryoglobulinemic Vasculitis Masquerading as Bilateral Carpal Tunnel Syndrome

Vohra

Attar

Katiyar

et al. 2019

Cureus

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Cryoglobulinemic vasculitis (CV) is a systemic inflammatory syndrome involving small-to medium-sized vessels. Almost half of hepatitis C-infected patients have detectable cryoglobulins levels, but only very few develop clinical manifestations. In this case report, we bring forth a diagnostic challenge of CV. A 52-year-old man with untreated hepatitis C (high viral load), diabetes mellitus, hypertension, and chronic kidney disease 4 (CKD) with solitary left kidney presented with one month of bilateral hand pain that started in his right hand, progressed to involve the left with numbness more on the palmer aspects and lateral three fingers. Physical exam was significant for bilateral positive Phalen and Tinel's sign. CV occurs due to precipitation of immune complexes within the vessels. Palpable purpura, arthralgia, and weakness have been described as the core symptoms of CV. However, progressive acute to subacute neuropathy, especially bilateral, should raise concerns for vasculitic neuropathy.

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Cryoglobulins: An update on detection, mechanisms and clinical contribution

Cited by 51 publications

References 58 publications

Cryoglobulins Today: Detection and Immunologic Characteristics of 1,675 Positive Samples From 13,439 Patients Obtained Over Six Years

Cryoglobulins Today: Detection and Immunologic Characteristics of 1,675 Positive Samples From 13,439 Patients Obtained Over Six Years

Benefit of direct-acting antiviral therapy for hepatitis C virus (HCV) in monoinfected and HIV-HCV-coinfected patients with mixed cryoglobulinaemia

Cryoglobulinemic Vasculitis Masquerading as Bilateral Carpal Tunnel Syndrome

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