Different biochemical patterns in type II and type III mixed cryoglobulinemia in HCV positive patients

Basile, Umberto; Gulli, Francesca; Gragnani, Laura; Pocino, Krizia; Napodano, Cecilia; Miele, Luca; Santini, Stefano Angelo; Marino, Mariapaola; Zignego, Anna Linda; Rapaccini, Gian Ludovico

doi:10.1016/j.dld.2018.03.028

Cited by 12 publications

(14 citation statements)

References 28 publications

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“…Infections, autoimmunity and cancer have been implicated as determinants of etiology in MC however; HCV is the most frequent infectious trigger (Gulli et al, 2017, Basile et al, 2018a, 2018b.…”

Section: Introductionmentioning

confidence: 99%

“…Due to the complex virus-host interactions, MC represents an excellent model to investigate the pathogenetic mechanisms of HCV infection and its evolution into autoimmune/lymphoproliferative disorders that are still poorly understood (Basile et al, 2018a(Basile et al, , 2018b. The clinical spectrum of MC is extremely wide, ranging from completely asymptomatic forms without vasculitis to life-threatening complications; the worsening evolution into B cell Non-Hodgkin's Lymphoma (B-NHL) occurs in about 10% of cases (Ramos-Casals et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Sentinel biomarkers in HCV positive patients with mixed cryoglobulinemia

Basile

Marino

Gragnani

et al. 2020

Journal of Immunological Methods

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Background: Infections, autoimmunity and cancer play a role as determinants of etiology in Hepatitis C virus (HCV) related mixed cryoglobulinemia (MC). Several factors of risk have been suggested as markers of pathogenesis and progression of HCV-related MC into B cell Non-Hodgkin's Lymphoma (B-NHL). Here, we evaluated IgG subclass distribution, free light chains (FLCs) and vascular endothelial growth factor (VEGF) as a new combination of biomarkers. Methods: We measured IgG1-4 subclasses, FLCs and VEGF levels in sera 53 from HCV-related MC, in comparison with 40 sera from HCV negative patients with rheumatoid arthritis (RA) and 30 from healthy blood donors (HBD). Results: IgG3 levels were significantly higher in HCV-MC patients with a decrement of IgG2 and IgG4; FLC levels significantly increased in both MC and RA patients' groups; serological VEGF was higher in HCV-MC patients than in HBD in correlation with k and λ levels. Conclusion:Our results suggest that a specific IgG subclasses pattern together with raised levels of FLCs and VEGF could represent the biomarker "signature" of an inflammation multistage of acquired immune system.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sentinel biomarkers in HCV positive patients with mixed cryoglobulinemia

Basile

Marino

Gragnani

et al. 2020

Journal of Immunological Methods

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“…The right strategy (drug and treatment) is the goal for a personalized medicine. Recently, we described different patterns of immunological biomarkers and liver fibrosis stage in HCV‐positive patients with type II and III MC . In the present study, analyzing serum samples from 79 HCV patients through a panel of biomarkers including FLCs, we aimed to identify different serological profiles as predictive factors between asymptomatic, with low levels, and symptomatic HCV patients exhibiting high levels of CGs.…”

Section: Introductionmentioning

confidence: 93%

Serological profile of asymptomatic HCV positive patients with low level of cryoglobulins

et al. 2018

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Clinical spectrum of hepatitis C virus (HCV)-related cryoglobulinemia varies from an asymptomatic presentation to severe vasculitis and lymphoma. A recent study in HCV-negative patients suggests that low cryoglobulins (CGs) levels are responsible for severe renal and neurological complications. The aim of this study was to identify a panel of serological biomarkers associated with low levels of CGs in HCV-positive patients. We studied a population of 79 untreated patients with chronic HCV infection: 13 naïve patients without CGs; 28 patients with asymptomatic mixed cryoglobulinemia (MC) and low levels of CGs (16/28 with polyclonal type III and 12/28 with microheterogeneous type III CGs); 38 patients with symptomatic MC and high levels of type II CGs. Serum samples were collected and examined for rheumatoid factor (RF) IgG and IgM, free light chains (FLCs) and C3 and C4 complement components. We found that RF-IgG and IgM, free k chains and k+λ were increased while C4 component was reduced, both in symptomatic and asymptomatic patients. Our results suggest that, even in absence of MC symptoms, the low levels of CGs may represent a trigger of activation for immune system in course of HCV infection. The identification of a correlated biomarkers panel could improve the clinical management of these patients and pave the way for target treatment strategies. © 2018 Bio-Factors, 45(3):318-325, 2019

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“…Cryoglobulins (CGs) are antibodies that precipitate in vitro at temperatures below 37°C and dissolve after rewarming ( 26 , 32 , 33 ). Their precipitation in vivo can cause vasculitis of small and medium-sized vessels in the skin, joints, nerves and kidneys ( 26 ), and consequently signs and symptoms such as intermittent purpura, livedo, leg ulcers, acrocyanosis, Raynaud’s phenomenon, arthralgias, and symptoms due to peripheral neuropathy ( 26 , 34 , 35 ).…”

Section: Introductionmentioning

confidence: 99%

Cold Agglutinins and Cryoglobulins Associate With Clinical and Laboratory Parameters of Cold Urticaria

et al. 2021

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Mast cell-activating signals in cold urticaria are not yet well defined and are likely to be heterogeneous. Cold agglutinins and cryoglobulins have been described as factors possibly associated with cold urticaria, but their relevance has not been explained. We performed a single-center prospective cohort study of 35 cold urticaria patients. Cold agglutinin and cryoglobulin test results, demographics, detailed history data, cold stimulation test results, complete blood count values, C-reactive protein, total immunoglobulin E levels, and basal serum tryptase levels were analyzed. Forty six percent (n = 16) of 35 tested patients had a positive cold agglutinin test and 27% (n = 9) of 33 tested patients had a positive cryoglobulin test. Cold agglutinin positive patients, when compared to cold agglutinin negative ones, were mainly female (P = 0.030). No gender-association was found for cryoglobulins. A positive cold agglutinin test, but not a positive cryoglobulin test, was associated with a higher rate of reactions triggered by cold ambient air (P = 0.009) or immersion in cold water (P = 0.041), and aggravated by increased summer humidity (P = 0.007). Additionally, patients with a positive cold agglutinin test had a higher frequency of angioedema triggered by ingestion of cold foods or drinks (P = 0.043), and lower disease control based on Urticaria Control Test (P = 0.023). Cold agglutinin levels correlated with erythrocyte counts (r = −0.372, P = 0.028) and monocyte counts (r = −0.425, P = 0.011). Cryoglobulin concentrations correlated with basal serum tryptase levels (r = 0.733, P = 0.025) and cold urticaria duration (r = 0.683, P = 0.042). Results of our study suggest that cold agglutinins and cryoglobulins, in a subpopulation of cold urticaria patients, are linked to the course and possibly the pathogenesis of their disease.

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Different biochemical patterns in type II and type III mixed cryoglobulinemia in HCV positive patients

Abstract: Results show a combination of biochemical markers and autoantibodies associated to mixed cryoglobulinemia; these findings could be further investigated in order to ascertain their usefulness in assessing the risk for the development of mixed cryoglobulinemia.

Cited by 12 publications

References 28 publications

Sentinel biomarkers in HCV positive patients with mixed cryoglobulinemia

Sentinel biomarkers in HCV positive patients with mixed cryoglobulinemia

Serological profile of asymptomatic HCV positive patients with low level of cryoglobulins

Cold Agglutinins and Cryoglobulins Associate With Clinical and Laboratory Parameters of Cold Urticaria

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