Superoxide Dismutase Prevents SARS-CoV-2-Induced Plasma Cell Apoptosis and Stabilizes Specific Antibody Induction.

The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.

IgG4-related disease: an atypical presentation of steroid-responsive renal mass.

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disease characterised by dense lymphoplasmacytic infiltration rich in IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. Serum IgG4 levels are typically elevated but half of the patients had normal serum IgG4 levels. IgG4-RD represents a spectrum of diseases that involve various organs such as the pancreas, liver, kidneys, and salivary glands often manifesting as diffuse organ enlargement or a mass-like lesion mimicking cancer. An increased incidence of malignancy among patients with IgG4-RD has been reported. Thus, differentiating malignancy from IgG4-RD manifestation is important as the treatment differs. Glucocorticoids are considered first-line therapy and should be started early to prevent fibrosis. Patients usually have an excellent clinical response to steroids, and poor steroid response is indicative of an alternative diagnoses such as malignancy. This case report describes a case of IgG4-RD with renal mass in a young man that resolved with glucocorticoid therapy alone.

B cell analysis in SARS-CoV-2 versus malaria: Increased frequencies of plasmablasts and atypical memory B cells in COVID-19.

B cells play a central role in antiviral and antiparasitic immunity, not only as producers of antibodies, but also as APCs and mediators of inflammation. In this study, we used 16-color flow cytometry analysis to investigate the frequency, differentiation, and activation status of peripheral B cells of patients with SARS-CoV-2 infection or acute Plasmodium falciparum malaria compared with the healthy individuals. As a main result, we observed an increase of the frequency of (CD27-, CD21-) atypical memory B cells and (CD19+, CD27+, CD38+) plasmablasts in malaria and COVID-19 patients. Additionally, CD86, PD-1, CXCR3, and CD39 expression was up-regulated, whereas CD73 was down-regulated on plasmablasts of COVID-19 and malaria patients compared with the bulk B cell population. In particular, there was a more pronounced loss of CD73+ B cells in malaria. The frequency of plasmablasts positively correlated with serum levels of CRP, IL-6, and LDH of COVID-19 patients. In the longitudinal course of COVID-19, a rapid normalization of the frequency of atypical memory B cells was observed. The role and function of plasmablasts and atypical memory B cells in COVID-19 and other acute infections remain to be further investigated. The role of B cells as either "driver or passenger" of hyperinflammation during COVID-19 needs to be clarified.

Peripheral Plasma Cells Associated with Mortality Benefit in Severe COVID-19: A Marker of Disease Resolution.

BACKGROUND: Cytokines seen in severe coronavirus disease 2019 (COVID-19) are associated with proliferation, differentiation, and survival of plasma cells. Plasma cells are not routinely found in peripheral blood, though may produce virus-neutralizing antibodies in COVID-19 later in the course of an infection. METHODS: Using the Johns Hopkins COVID-19 Precision Medicine Analytics Platform Registry, we identified hospitalized adult patients with confirmed severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and stratified by presence of plasma cells and World Health Organization (WHO) disease severity. To identify plasma cells, we employed a sensitive flow cytometric screening method for highly fluorescent lymphocytes and confirmed these microscopically. Cox regression models were used to evaluate time to death and time to clinical improvement by the presence of plasma cells in patients with severe disease. RESULTS: Of 2301 hospitalized patients with confirmed infection, 371 had plasma cells identified. Patients with plasma cells were more likely to have severe disease, though 86.6% developed plasma cells after onset of severe disease. In patients with severe disease, after adjusting for age, sex, body mass index, race, and other covariates associated with disease severity, patients with plasma cells had a reduced hazard of death (adjusted hazard ratio: 0.57; 95% confidence interval: 0.38-0.87; P value: .008). There was no significant association with the presence of plasma cells and time to clinical improvement. CONCLUSIONS: Patients with severe disease who have detectable plasma cells in the peripheral blood have improved mortality despite adjusting for known covariates associated with disease severity in COVID-19. Further investigation is warranted to understand the role of plasma cells in the immune response to COVID-19.

[Treatment of early relapsed plasma cells leukemia after unrelated bone marrow transplant with KRD (carfilzomib, lenalidomide and dexamethasone): a case report.] / Trattamento della leucemia plasmacellulare in recidiva precoce dopo trapianto di midollo osseo allogenico da donatore non correlato con KRD (carfilzomib, lenalidomide e desametasone): un caso clinico.

INTRODUCTION: Plasma cell leukemia (PCL) is a rare but most aggressive form of monoclonal gammopathies, characterized by the presence of clonal cells in peripheral blood and a poor prognosis. There are two forms of PCL: primary, which arise de novo, and secondary which is a leukemic transformation in patients with previously multiple myeloma. Patients with PCL may benefit from stem cell transplantation and novel agents, but their prognosis remains inferior to that of patients who have multiple myeloma. CLINICAL CASE: We describe the case of 53 years old patient with relapsed plasma cells leukemia after unrelated bone marrow transplant, treated with a KRD chemotherapy regimen. He performed a very good response after the first 2 cycles (bone marrow malignant plasma cells reducing from 36% to 0.5%). However, according to the very poor prognosis of this disease, after the 4th cycle of chemotherapy the patient progressed and dead into few weeks. The KRD regimen was able to convert the chimerism after bone marrow transplant from partial to complete after the first 2 cycles of treatment, showing some activity in this disease. CONCLUSIONS: KRD regimen, in our clinical case, showed some activity being well tolerated in a very poor prognosis disease such as PCL. Probably, right use and maybe sooner use of new drugs such as bortezomib or carfilzomib, in combination regimens, may be useful in better treating such disease.