Hepatitis B virus causes mixed cryoglobulinaemia by driving clonal expansion of innate B-cells producing a VH1-69-encoded antibody.

OBJECTIVES: To investigate the expression of a VH1-69-encoded idiotype, and the phenotypic and functional features of monoclonal B-cells from patients with type II mixed cryoglobulinaemia (MC) secondary to chronic hepatitis B virus (HBV) infection. METHODS: B-cell immunophenotype and expression of a VH1-69-encoded idiotype were investigated by flow cytometry. B-cell proliferative responses to stimuli were investigated by the CFSE dilution assay. RESULTS: Two out of five patients with chronic HBV studied had massive monoclonal expansion of VH1-69-expressing B-cells. These cells had the peculiar CD21(low) phenotype and low responsiveness to stimuli typical of the VH1-69-expressing B-cells commonly expanded in MC secondary to hepatitis C virus (HCV) infection. In both patients, anti-HBV therapy led to the regression of MC and of VH1-69+ B-cell expansion. CONCLUSIONS: VH1-69-encoded antibodies are known to preferentially recognise a variety of viral proteins including HCV E2, influenza A virus haemagglutinin and HIV gp41/gp120, and may serve as innate first line antiviral defense. Thus, like HCV, HBV may cause MC by protracted antigenic stimulation of VH1-69-expressing B-cells.

COVID-19 and Immunological Dysregulation: Can Autoantibodies be Useful?

Coronavirus disease 2019 (COVID-19) is often associated with interstitial pneumonia. However, there is insufficient knowledge on the presence of autoimmune serological markers in patients with COVID-19. We analyzed the presence and role of autoantibodies in patients with COVID-19-associated pneumonia. We prospectively studied 33 consecutive patients with COVID-19, 31 (94%) of whom had interstitial pneumonia, and 25 age-matched and sex-matched patients with fever and/or pneumonia with etiologies other than COVID-19 as the pathological control group. All patients were tested for the presence of antinuclear antibodies (ANAs), anti-antiphospholipid antibodies, and anti-cytoplasmic neutrophil antibodies (ANCAs). Clinical, biochemical, and radiological parameters were also collected. Fifteen of 33 patients (45%) tested positive for at least one autoantibody, including 11 who tested positive for ANAs (33%), 8 who tested positive for anti-cardiolipin antibodies (immunoglobulin (Ig)G and/or IgM; 24%), and 3 who tested positive for anti-ß2-glycoprotein antibodies (IgG and/or IgM; 9%). ANCA reactivity was not detected in any patient. Patients that tested positive for auto-antibodies had a significantly more severe prognosis than other patients did: 6 of 15 patients (40%) with auto-antibodies died due to COVID-19 complications during hospitalization, whereas only 1 of 18 patients (5.5%) who did not have auto-antibodies died (P = 0.03). Patients with poor prognosis (death due to COVID-19 complications) had a significantly higher respiratory rate at admission (23 breaths per minute vs. 17 breaths per minute; P = 0.03) and a higher frequency of auto-antibodies (86% vs. 27%; P = 0.008). In conclusion, auto-antibodies are frequently detected in patients with COVID-19 possibly reflecting a pathogenetic role of immune dysregulation. However, given the small number of patients, the association of auto-antibodies with an unfavorable prognosis requires further multicenter studies.