Systemic Autoimmune Diseases in Patients with Hepatitis C Virus Infection: Characterization of 1020 Cases (The HISPAMEC Registry)

Ramos-Casals, Manuel; Muñoz, Sandra; Medina, Francisco J.; Jara, Luis-Javier; Rosas, José; Calvo‐Alén, Jaime; Brito-Zerón, Pilar; Forns, Xavier; Sánchez-Tapias, José-Marı́a

doi:10.3899/jrheum.080874

Cited by 142 publications

(88 citation statements)

References 40 publications

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“…wise underutilized in clinical practice (13). CG testing is often neglected by clinicians because of the long duration of the testing procedure and the rare positive results.…”

Section: Discussionmentioning

confidence: 99%

Detection of low level cryoglobulins by flow cytometry

et al. 2012

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Several patients with cryoglobulin (CG) associated symptoms are seronegative for CG and other potentially causative biomarkers. We analyzed whether it is possible to detect cryoprecipitates by flow cytometry and whether the sensitivity of their demonstration can be increased as compared to visual inspection. Sera from 91 patients with suspected CG associated symptoms and 33 healthy controls were examined for the presence of CG by conventional visual testing and by flow cytometry for small diffracting particles. For calibration purposes we tested lipid micelle dilutions (positive controls) by both methods. The minimum concentrations of lipid micelles to be detected by visual inspection and flow cytometry were 128.5 and 2.0 pg ml 21 , respectively. Among the 91 patients and 33 controls, only 1 patient serum was positive for CG by conventional testing. This sample was also positive on flow cytometry. In the serum of a patient known to be positive for CG, laser diffracting particles were quantified by flow cytometry after keeping serum at 48C for 3 days. Of the 91 patients, 14 additional samples displayed cold precipitates which redissolved after rewarming during flow cytometry. All 15 (1 1 14) patients positive for CG on flow cytometry suffered from symptoms usually associated with CG. Some precipitates were labeled with anti IgG and IgM antibodies confirming that the particles detected by flow cytometry contained immunoglobulins. No small diffracting particles were detected in the sera of the 33 healthy controls. Flow cytometry is equally specific but much more sensitive in the detection of CG than visual inspection. ' 2012 International Society for Advancement of Cytometry Key termscryoglobulins; flow cytometry CRYOGLOBULINS (CG) are associated with various diseases, such as immunoproliferative disorders (e.g., multiple myeloma) and several autoimmune diseases (e.g., vasculitis) (1). Especially during hepatitis C virus (HCV) infection, CG are associated with a variety of extrahepatic manifestations including vasculitis, glomerulonephritis, arthritis, and peripheral neuropathy (2,3). CG are serum immunoglobulins that precipitate if the temperature drops substantially below body temperature. CG dissolves during rewarming. After in vivo precipitation of CG in small vessels, neutrophils and mononuclear cells home to these sites and lead to the induction of inflammation of small vessels. Consequently, a sensitive detection of CG is an important contribution to the diagnostic procedures for vasculitis.Today, the detection of CG is performed by visual inspection of precipitates formed in cooled serum as compared with serum kept at 378C. Redissolving of the precipitate after rewarming to 378C excludes unspecific aggregates and confirms the CG nature of the precipitates (4). Interestingly, it has been reported that CG can also be detected in blood smears (5,6). Two major disadvantages of the visual inspection method are their low detection rate and its semiquantitative nature. Alternatively, CG can be quantified b...

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“…wise underutilized in clinical practice (13). CG testing is often neglected by clinicians because of the long duration of the testing procedure and the rare positive results.…”

Section: Discussionmentioning

confidence: 99%

Detection of low level cryoglobulins by flow cytometry

et al. 2012

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“…Circulating autoantibodies, including antinuclear antibodies (ANA), RF, antiphospholipid (aPL) antibodies, cryoglobulins, anti-smooth muscle actin (SMA) antibodies, liver-kidney microsomal antibodies (LKM), and antithyroid peroxidase, are often detected in patients with chronic HCV infection [3,74,75]. ANA, RF and SMA are the most common.…”

Section: Autoantibodies Associated With Chronic Hcv Infectionmentioning

confidence: 99%

“…A high degree of association between HCV infection and SS, SLE and rheumatoid arthritis (RA) has been described. The main differential aspect between primary and HCV-associated SAD is the dominance of cryoglobulinaemia-related markers (cryoglobulins, RF, hypocomplementaemia) over specific SAD-related markers (anti-extractable nuclear antigen antibody, anti-dsDNA, anticyclic citrullinated peptide) in patients with HCV [75].…”

Section: Systemic Autoimmune Diseases During Hcv Infectionmentioning

confidence: 99%

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Hepatitis C virus and autoimmunity

Böckle

Sepp

2010

Autoimmun Highlights

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Hepatitis C virus infection is associated with several extrahepatic manifestations. About 60% of patients infected with HCV develop at least one extrahepatic manifestation. The majority of these diseases seem to be triggered through autoimmune mechanisms, such as autoantibody production, autoreactive T cells and complex autoimmune mechanisms leading to systemic autoimmune disorders. In this review we categorize these diseases into three groups according to the main pathogenetic process involved, in particular B-cell-mediated, T-cell-mediated and complex autoimmune systemic diseases.

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“…Hyperactivation and/or hyperproliferation of B-cells induces the selective expansion of B-cell clone(s), which in turn produce cryoglobulins (9,20).…”

Section: Etiology and Pathogenesismentioning

confidence: 99%

Cryoglobulinemia (Review)

Takada

Shimizu²,

Hadano³

et al. 2012

Mol Med Report

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Abstract.Cryoglobulins are immunoglobulins that precipitate at low temperatures and redissolve upon rewarming. Cryoglobulinemia refers to the presence of circulating cryoglobulins in serum, and generally leads to a systemic inflammatory syndrome characterized by fatigue, arthralgia, purpura, neuropathy and glomerulonephritis. The disease mainly involves small to medium-sized blood vessels and causes vasculitis due to cryoglobulin-containing immune complexes. Cryoglobulinemia is classified into three types (I, II and III) on the basis of immunoglobulin composition. Predisposing conditions include lymphoproliferative disease, collagen disease and hepatitis C virus (HCV) infection. The diagnosis of cryoglobulinemic syndrome is predominantly based on the laboratory demonstration of serum cryoglobulins. Treatment is often directed towards the underlying disease state. For patients with chronic HCV infection, anti-viral therapy is indicated. Intense immunosuppressive or immunomodulatory therapy, including steroids, plasmapheresis and cytotoxic agents, is reserved for organ-threatening or recalcitrant disease. In this review, we discuss the clinical characteristics of the three types of cryoglobulinemia.

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Systemic Autoimmune Diseases in Patients with Hepatitis C Virus Infection: Characterization of 1020 Cases (The HISPAMEC Registry)

Cited by 142 publications

References 40 publications

Detection of low level cryoglobulins by flow cytometry

Detection of low level cryoglobulins by flow cytometry

Hepatitis C virus and autoimmunity

Cryoglobulinemia (Review)

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