Solving the mystery of HBV-related mixed cryoglobulinemia: potential biomarkers of disease progression

Pocino, Krizia; Napodano, Cecilia; Gragnani, Laura; Ciasca, Gabriele; Colantuono, Stefania; Marri, Silvia; Vantaggio, Lorenzo; Gulli, Francesca; Lorini, Serena; Barini, Angelina; Stefanile, Annunziata; Miele, Luca; Casato, Milvia; Zignego, Anna Linda; Rapaccini, Gian Ludovico; Marino, Mariapaola; Visentini, Marcella; Basile, Umberto

doi:10.1093/rheumatology/keab157

Cited by 9 publications

(5 citation statements)

References 43 publications

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“…IgG3, free light chains and VEGF levels were significantly higher in HCV-related CV patients than in healthy controls [29]. Similar preliminary results have been found in HBV-related CV [30].…”

Section: Pathophysiology and Diagnostic Biomarkerssupporting

confidence: 85%

Cryoglobulinemic vasculitis: a 2023 update

Moretti,

Ferro,

Baldini

et al. 2023

Current Opinion in Rheumatology

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Purpose of review Cryoglobulinemic vasculitis (CV) is an immune complex mediated small vessel vasculitis characterized by the presence of cryoglobulins in serum, often associated with hepatitis C infection, systemic autoimmune diseases or hematological conditions. The focus of this review is to provide an update on new insights into pathogenesis, epidemiology and therapies of infectious and noninfectious type II and type III CV. Recent findings The introduction of new antiviral drugs for treatment of hepatitis C infection implied major changes in HCV-related CV, allowing to shed new lights on CV pathogenesis and mechanisms of relapse and, therefore, to increase the relevance of autoimmune diseases in CV epidemiology. Specific B-cell clones are involved in the production of pathogenic immune complexes that leads to small-vessel vasculitis. Therefore, both antiviral treatments [direct-acting antivirals (DAAs) and oral nucleot(s)ide analogues] and targeted anti-CD20 therapies (rituximab) prove to be safe and effective options, leading to a better prognosis. Association of Sjögren syndrome and CV defines a specific phenotype of patients, characterized by severe manifestations and poor outcome. Summary Removing viral stimulation on B-cells through direct-acting antivirals and blocking B-cells proliferation and differentiation with rituximab are the goals of treatment of CV. However, further research is needed to identify prognostic factors of refractory and relapsing disease.

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Section: Pathophysiology and Diagnostic Biomarkerssupporting

confidence: 85%

Cryoglobulinemic vasculitis: a 2023 update

Moretti,

Ferro,

Baldini

et al. 2023

Current Opinion in Rheumatology

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“…ROC curves and AUC values were calculated as previously described (15)(16)(17)and using the R package pROC. Stepwise backward logistic regression was used to select the best subset of biomarkers according to the Aikake's Information Criterium (AIC) (18). The optimal cut-off is calculated by a maximization of the Youden's statistics J = sensitivity+specificity -1.…”

Section: Discussionmentioning

confidence: 99%

Salivary biomarkers in COVID-19 patients: the rabbit out of the hat!

Napodano,

Callà,

Fiorito

et al. 2024

Preprint

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Background: The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) represents a major threat to human health, which impairs the functionality of several organs. One of the hardest challenges in the fight against COVID-19 is the development of wide-scale, effective, and rapid laboratory tests to control disease severity, progression, and possible sudden worsening. Monitoring patients in real-time is indeed highly demanded in this pandemic era when physicians need reliable and quantitative tools to prioritize patients’ access to intensive care departments. In this regard, salivary biomarkers are extremely promising, as they allow for a fast and non-invasive specimens’ collection, which can be repeated multiple times. Methods: We compare salivary levels of immunoglobulin A subclasses (IgA1 and IgA2) and free-light chains (FLC k and λ) in a cohort of 29 SARS-CoV-2 patients and 21 healthy subjects. Results: We found that each biomarkers differs significantly between the two groups, with p-values ranging from 10-8 to 10-4. The performance ranking of these markers, shows that λFLC level (p=1.4e-8) is the best-suited candidate to discriminate the two groups, with an accuracy of 0.94 (0.87-1.00 95% CI), a precision of 0.91 (0.81-1.00 95% CI), a sensitivity of 1.00 (0.96-1.00 95% CI) and a specificity of 0.86 (0.70-1.00 95% CI). Conclusion: These results suggest λFLC as an ideal indicator of patient conditions. This is more strengthened in consideration that λFLC half-life (approximately 6 hours) is significantly shorter than the IgA one (21 days): thus λFLC appears displaying the potential to effectively monitor patients fluctuation in real-time

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“…The quantification of free light chain levels (κ and λ) from the serum of both patients and controls followed previously established methods [21,22]. Briefly, the collected samples were centrifuged at 2500× g for 10 min.…”

Section: Laboratory Testingmentioning

confidence: 99%

Serum Neurofilament and Free Light Chain Levels in Patients Undergoing Treatment for Chronic Inflammatory Demyelinating Polyneuropathy

Luigetti,

Primiano,

Basile

et al. 2024

IJMS

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Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder affecting the peripheral nervous system. Despite the established diagnostic criteria, monitoring disease activity and treatment remains challenging. To address this limitation, we investigated serum neurofilament light chain (sNfL) and serum free light chains (sFLCs) as potential biomarkers. A total of 32 CIDP patients undergoing immunoglobulin therapy and 32 healthy controls enrolled in the present study, and agreed to have their blood plasma sNfL and sFLCs analyzed, while CIDP severity was assessed through the modified Rankin Scale (mRS) and the Overall Neuropathy Limitations Scale (ONLS). In line with the immunoglobulin treatment aimed at limiting neuronal damage administered to the majority of patients, sNfL levels did not exhibit significant differences between the two groups. However, CIDP patients showed significantly elevated sFLC and sFLC ratios, while the marker levels did not correlate with the clinical scores. The study confirms the potential of sFLCs as a sensitive biomarker of inflammatory processes in CIDP. Additionally, the present study results regarding neurofilaments strengthen the role of sNfL in monitoring CIDP treatments, confirming the effectiveness of immunoglobulin therapy. Overall, our results demonstrate how combining these markers can lead to better patient characterization for improved treatment.

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Solving the mystery of HBV-related mixed cryoglobulinemia: potential biomarkers of disease progression

Cited by 9 publications

References 43 publications

Cryoglobulinemic vasculitis: a 2023 update

Cryoglobulinemic vasculitis: a 2023 update

Salivary biomarkers in COVID-19 patients: the rabbit out of the hat!

Serum Neurofilament and Free Light Chain Levels in Patients Undergoing Treatment for Chronic Inflammatory Demyelinating Polyneuropathy

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