Inactivated SARS-CoV-2 vaccine does not influence the profile of prothrombotic antibody nor increase the risk of thrombosis in a prospective Chinese cohort

The presence of antiphospholipid antibodies was shown to be associated with thrombosis in coronavirus disease 2019(COVID-19)patients.Recently,according to reports from several studies,the vaccineinduced immune thrombotic thrombocytopenia is mediated by anti-platelet factor 4(PF4)-polyanion complex in adenovirus-vectored COVID-19 vaccine recipients.It is impendent to explore whether inactivated COVID-19 vaccine widely used in China influences prothrombotic autoantibody production and induces thrombosis.In this prospective study,we recruited 406 healthcare workers who received two doses,21 days apart,of inactivated severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine(BBIBP-CorV,Sinopharm).Paired blood samples taken before vaccination and four weeks after the second vaccination were used in detecting prothrombotic autoantibodies,including anticardiolipin(aCL),anti-b2 glycoprotein I(ab2GP1),anti-phosphatidylserine/prothrombin(aPS/PT),and anti-PF4-heparin.The seroconversion rate of SARS-CoV-2 specific antibodies was 95.81%(389/406)four weeks after vaccination.None of the subjects had spontaneous thrombosis or thrombocytopenia over a minimum follow-up period of eight weeks.There was no significant difference in the presence of all ten autoantibodies between samples collected before and after vaccination:for aCL,IgG(7 vs.8,P=0.76),IgM(41 vs.44,P=0.73),IgA(4 vs.4,P=1.00);anti-b2GP1,IgG(7 vs.6,P=0.78),IgM(6 vs.5,P=0.76),IgA(3 vs.5,P=0.72);aPS/PT IgG(0 vs.0,P=1.00),IgM(6 vs.5,P=0.76);aPF4-heparin(2 vs.7,P=0.18),and antinuclear antibody(ANA)(18 vs.21,P=0.62).Notably,seven cases presented with anti-PF4-heparin antibodies(range:1.18–1.79 U/mL)after vaccination,and none of them exhibited any sign of thrombotic disorder.In conclusion,inactivated SARS-CoV-2 vaccine does not influence the profile of antiphospholipid antibody and anti-PF4-heparin antibody nor increase the risk of thrombosis.

Presence of multiple abnormal immunologic markers is an independent prognostic factor of diffuse large B-cell lymphoma

Autoimmune diseases (ADs) increase the risk of non-Hodgkin's lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investigated. This study aims to analyze the prognostic value of pretreatment immunologic markers in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed the data on 502 patients with DLBCL treated in our institution from January 2013 to March 2018. Survival functions were estimated using Kaplan Meier method and Cox regression model. The 3-year progression free survival (PFS) and overall survival (OS) rates were 70.2% and 80.9%, respectively, and the complete remission (CR) rate was 78.1%. Among the patients, those with multiple (≥3) abnormal immunologic markers had significantly shorter 3-year PFS (52.7% vs. 77.3%, P < 0.001) and OS (68.5% vs. 85.8%, P=0.001) than those without multiple abnormal immunologic markers.Multivariate analysis revealed that the presence of multiple abnormal immunologic markers and the elevated serum levels of lactate dehydrogenase were the independent adverse prognostic factors for PFS (P= 0.008, P < 0.001) and OS (P = 0.003, P < 0.001). Meanwhile, advanced Ann Arbor stage was an independent adverse prognostic factor for PFS (P= 0.001) and age > 60 years for OS (P= 0.014). In conclusion, the immunologic status was closely related to lymphoma progression, and this study provides new insights into the risk stratification of patients with DLBCL.

Continuation,reduction,or withdrawal of tofacitinib in patients with rheumatoid arthritis achieving sustained disease control:a multicenter,open-label,randomized controlled trial

Background:Rheumatoid arthritis(RA),a chronic systemic autoimmune disease,is characterized by synovitis and progressive damage to the bone and cartilage of the joints,leading to disability and reduced quality of life.This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control.Methods:The study was designed as a multicenter,open-label,randomized controlled trial.Eligible patients who were taking tofacitinib(5 mg twice daily)and had achieved sustained RA remission or low disease activity(disease activity score in 28 joints[DAS28]≤3.2)for at least 3 months were enrolled at six centers in Shanghai,China.Patients were randomly assigned(1:1:1)to one of three treatment groups:continuation of tofacitinib(5 mg twice daily);reduction in tofacitinib dose(5 mg daily);and withdrawal of tofacitinib.Efficacy and safety were assessed up to 6 months.Results:Overall,122 eligible patients were enrolled,with 41 in the continuation group,42 in the dose-reduction group,and 39 in the withdrawal group.After 6 months,the percentage of patients with a DAS28-erythrocyte sedimentation rate(ESR)of<3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups(20.5%,64.3%,and 95.1%,respectively;P<0.0001 for both comparisons).The average flare-free time was 5.8 months for the continuation group,4.7 months for the dose reduction group,and 2.4 months for the withdrawal group.Conclusion:Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy,while standard or reduced doses of tofacitinib maintained a favorable state.Trial Registration:Chictr.org,ChiCTR2000039799.