Effect of COVID-19 vaccination on viral clearance and antibody production in older patients with SARS-CoV-2 infection

Whether coronavirus disease 2019 (COVID-19) vaccination promotes viral clearance in older patients has not been reported. We performed a retrospective review of patients hospitalized with COVID-19. This study included 24 patients with COVID-19 admitted to Hiroshima City Funairi Citizens Hospital between June 1 and July 10, 2021. Nine patients who were vaccinated (median age: 72 years) were compared with 15 patients who were not vaccinated (median age: 70 years). Viral clearance was confirmed by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR). Antibody titers were measured to assess vaccination efficacy. The vaccinated group had a higher negative conversion rate than that in the non-vaccinated group on RT-PCR testing before discharge (83% vs. 36%, P = 0.064). Antibody titers on admission and 10 ± 2 days after onset were significantly higher in the vaccinated group than those in the non-vaccinated group (35 vs. 0 binding antibody units (BAU)/mL, P = 0.012; and 114 vs. 7 BAU/mL, P = 0.032, respectively). Stimulating antibody production by vaccination may promote faster viral clearance in older patients who develop COVID-19.This research was funded by “Advanced study aim to contribute creating new evidence in COVID-19 based on the local government-academia collaboration research system in Hiroshima”: AMED Research Program on Emerging and Re-emerging Infectious Diseases, Grant Number JP20fk0108453

Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin β subunits

Integrins connect the extracellular matrix with the cell interior, and transduce signals through interactions of their cytoplasmic tails with cytoskeletal and signaling proteins. Using the yeast two-hybrid system, we isolated a novel splice variant (filamin-Bvar-1) of the filamentous actin cross-linking protein, filamin-B, that interacts with the cytoplasmic domain of the integrin β1A and β1D subunits. RT-PCR analysis showed weak, but wide, expression of filamin-Bvar-1 and a similar splice variant of filamin-A (filamin-Avar-1) in human tissues. Furthermore, alternative splice variants of filamin-B and filamin-C, from which the flexible hinge-1 region is deleted (ΔH1), were induced during in vitro differentiation of C2C12 mouse myoblasts. We show that both filamin-Avar-1 and filamin-Bvar-1 bind more strongly than their wild-type isoforms to different integrin β subunits. The mere presence of the high-affinity binding site for β1A is not sufficient for targeting the filamin-Bvar-1 construct to focal contacts. Interestingly, the simultaneous deletion of the H1 region is required for the localization of filamin-B at the tips of actin stress fibers. When expressed in C2C12 cells, filamin-Bvar-1(ΔH1) accelerates their differentiation into myotubes. Furthermore, filamin-B variants lacking the H1 region induce the formation of thinner myotubes than those in cells containing variants with this region. These findings suggest that specific combinations of filamin mRNA splicing events modulate the organization of the actin cytoskeleton and the binding affinity for integrins

High-dose Dexamethasone Therapy as the Initial Treatment for Idiopathic Thrombocytopenic Purpura: Protocol for a Multicenter, Open-label, Single Arm Trial

Standard therapy for idiopathic thrombocytopenic purpura (ITP) has not been established. We are conducting a multicenter, prospective trial to determine the efficacy and safety of short-term, high-dose dexamethasone therapy in ITP patients aged 18-80 years with platelet counts of <20, 000 /μL, or with <50, 000/ μL and bleeding symptoms. The primary endpoints of this trial are the proportion of responses (complete plus partial response) on day 180 (day 46+180) after the completion of the 46-day high-dose dexamethasone therapy. The results of this investigation of the effectiveness and safety of this regimen will be essential for the establishment of standard therapy for ITP

Multi-phasic gene profiling using candidate gene approach predict the capacity of specific antibody production and maintenance following COVID-19 vaccination in Japanese population

BackgroundVaccination against severe acute respiratory syndrome coronavirus type 2 is highly effective in preventing infection and reducing the severity of coronavirus disease (COVID-19). However, acquired humoral immunity wanes within six months. Focusing on the different tempo of acquisition and attenuation of specific antibody titers in individuals, we investigated the impact of genetic polymorphisms on antibody production after COVID-19 vaccination.MethodsIn total 236 healthcare workers from a Japanese municipal hospital, who received two doses of the vaccine were recruited. We employed a candidate gene approach to identify the target genetic polymorphisms affecting antibody production after vaccination. DNA samples from the study populations were genotyped for 33 polymorphisms in 15 distinct candidate genes encoding proteins involved in antigen-presenting cell activation, T cell activation, T-B interaction, and B cell survival. We measured total anti-SARS-Cov2 spike IgG antibody titers and analyzed the association with genetic polymorphisms at several time points after vaccination using an unbiased statistical method, and stepwise logistic regression following multivariate regression.ResultsSignificant associations were observed between seven SNPs in NLRP3, OAS1, IL12B, CTLA4, and IL4, and antibody titers at 3 weeks after the first vaccination as an initial response. Six SNPs in NLRP3, TNF, OAS1, IL12B, and CTLA4 were associated with high responders with serum antibody titer &gt; 4000 BAU/ml as boosting effect at 3 weeks after the second vaccination. Analysis of long-term maintenance showed the significance of the three SNPs in IL12B, IL7R, and MIF for the maintenance of antibody titers and that in BAFF for attenuation of neutralizing antibodies. Finally, we proposed a predictive model composed of gene profiles to identify the individuals with rapid antibody attenuation by receiver operating characteristic (ROC) analysis (area under the curve (AUC)= 0.76, sensitivity = 82.5%, specificity=67.8%).ConclusionsThe candidate gene approach successfully showed shifting responsible gene profiles and initial and boosting effect mainly related to the priming phase into antibody maintenance including B cell survival, which traces the phase of immune reactions. These gene profiles provide valuable information for further investigation of humoral immunity against COVID-19 and for building a strategy for personalized vaccine schedules

Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin

gamma-Filamin, also called ABP-L, is a filamin isoform that is specifically expressed in striated muscles, where it is predominantly localized in myofibrillar Z-discs. A minor fraction of the protein shows subsarcolemmal localization. Although gamma-filamin has the same overall structure as the two other known isoforms, it is the only isoform that carries a unique insertion in its immunoglobulin (Ig)-like domain 20. Sequencing of the genomic region encoding this part of the molecule shows that this insert is encoded by an extra exon. Transient transfections of the insert-bearing domain in skeletal muscle cells and cardiomyocytes show that this single domain is sufficient for targeting to developing and mature Z-discs. The yeast two-hybrid method was used to identify possible binding partners for the insert-bearing Ig-like domain 20 of gamma-filamin. The two Ig-like domains of the recently described alpha-actinin-binding Z-disc protein myotilin were found to interact directly with this filamin domain, indicating that the amino-terminal end of gamma-filamin may be indirectly anchored to alpha-actinin in the Z-disc via myotilin. Since defects in the myotilin gene were recently reported to cause a form of autosomal dominant limb-girdle muscular dystrophy, our findings provide a further contribution to the molecular understanding of this disease

Filamins Regulate Cell Spreading and Initiation of Cell Migration

Mammalian filamins (FLNs) are a family of three large actin-binding proteins. FLNa, the founding member of the family, was implicated in migration by cell biological analyses and the identification of FLNA mutations in the neuronal migration disorder periventricular heterotopia. However, recent knockout studies have questioned the relevance of FLNa to cell migration. Here we have used shRNA-mediated knockdown of FLNa, FLNb or FLNa and FLNb, or, alternatively, acute proteasomal degradation of all three FLNs, to generate FLN-deficient cells and assess their ability to migrate. We report that loss of FLNa or FLNb has little effect on migration but that knockdown of FLNa and FLNb, or proteolysis of all three FLNs, impairs migration. The observed defect is primarily a deficiency in initiation of motility rather than a problem with maintenance of locomotion speed. FLN-deficient cells are also impaired in spreading. Re-expression of full length FLNa, but not re-expression of a mutated FLNa lacking immunoglobulin domains 19 to 21, reverts both the spreading and the inhibition of initiation of migration

Solitary Pyomyositis of the Left Rhomboideus Muscle Caused by Streptococcus anginosus and Streptococcus intermedius in an Immunocompetent Person

Primary pyomyositis is a bacterial infection of the skeletal muscle commonly affecting children with Staphylococcus aureus most often isolated as a pathogen. However, pyomyositis caused by anaerobic bacteria is rare in adults. Here, we report a case of solitary Pyomyositis of the left rhomboideus muscle in an immunocompetent person. A 70-year-old Japanese male presented with high fever and left shoulder pain. His muscle below the lower edge of the left scapula was tender and swollen. His laboratory examinations revealed severe inflammation. Computed tomography showed a solitary low-density area around a contrast enhancement in the left rhomboideus muscle. He was diagnosed as having solitary pyomyositis. Although his symptoms did not improve despite empiric intravenous administration of antibiotics, an incision was performed. Streptococcus anginosus and Streptococcus intermedius were isolated from the culture of drainage fluid. His symptoms gradually disappeared after the incisional drainage and continuous administration of antibiotics. Pyomyositis did not recur after his discharge. To the best of our knowledge, this is the first report on anaerobic pyomyositis of the shoulder muscle

Anti-endothelial cell antibodies in Behcet's disease

Objective. Circulating antibodies that bind to human endothelial cells cultured in vitro have been detected in a variety of diseases, including Behcet's disease. In this disorder the reported prevalence of AECA has varied widely. One likely source of variability is the ELISA assay itself in which differing conditions and reagents have been used in different reports

Histological Progression of Follicular Lymphoma Associated with p53 Mutation and Rearrangement of the C-MYC Gene

Follicular lymphoma is a low grade malignant lymphoma. However, some follicular lymphomas undergo histological transformation into higher grade malignant lymphomas. We recently encountered a diffuse large cell lymphoma which seemed to have progressed from a follicular lymphoma and which finally transformed into a small non-cleaved lymphoma. Each stage of the histological transformation was accompanied by increasing clinical grades of malignancy. It was suspected that in our patient a follicular lymphoma initially developed due to rearrangement of the BCL2 gene, and then underwent histological transformation into a diffuse large cell lymphoma, which was associated with p53 mutation. Subsequent rearrangement of C-MYC promoted the histological transformation of this diffuse large cell lymphoma into a small non-cleaved lymphoma. Our findings indicate that p53 mutation and rearrangement of C-MYC are involved in the histological transformation of follicular lymphomas into more advanced lymphomas