Clinical application of SARS-CoV-2 antibody detection and monoclonal antibody therapies against COVID-19

The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.

Immunological pathogenesis and treatment of systemic lupus erythematosus

Background Systemic lupus erythematosis(SLE)is a complex and clinically heterogeneous autoimmune disease.A variety of immunological defects contribute to SLE,including dysregulated innate and adaptive immune response.A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated progress towards improved SLE-personalized approaches to treatment.The aim of this review was to clarify the immunological pathogenesis and treatment of SLE.Data sources Literature reviews and original research articles were collected from database,including PubMed and Wanfang.Relevant articles about SLE were included.Results Breakdown of self-tolerance is the main pathogenesis of SLE.The innate and adaptive immune networks are interlinked with each other through cytokines,complements,immune complexes and kinases of the intracellular machinery.Treatments targeted at possible targets of immunity have been assessed in clinical trials.Most of them did not show better safety and efficacy than traditional treatments.However,novel targeting treatments are still being explored.Conclusions Dysregulated immune response plays a critical role in SLE,including innate immunity and adaptive immunity.Biologic agents that aim to specifically target abnormal immune processes were assessing and may bring new hope to SLE patients.

T cells from induced and spontaneous models of SLE recognize a common T cell epitope on β2-glycoprotein Ⅰ

Systemic lupus erythematosus is a prototypic model for B-cell epitope spread in autoimmunity.Autoantibodies to numerous molecularly distinct self-antigens emerge in a sequential manner over several years,leading to disease manifestations.Among the earliest autoantibodies to appear are those targeting phospholipid-binding proteins,particularlyβ2-glycoprotein Ⅰ.Notably,mice immunized with β2-glycoprotein Ⅰ and lipopolysaccharide develop a strong T cell response to β2-glycoprotein Ⅰ that is associated with autoantibody production and renal disease,similar to that seen in human SLE.Here we hypothesized that mice with murine systemic lupus erythematosus,whether induced or spontaneous,should have T cells that recognizeβ2-glycoprotein I.We evaluated the response of splenic T cells from mice with induced(C57BL/6 and C3H/HeN)and spontaneous(MRL/lpr)systemic lupus erythematosus to peptides spanning the entire sequence of humanβ2GPI.We found that mice with induced and spontaneous systemic lupus erythematosus recognize a common T cell epitope(peptide 31;LYRDTAVFECLPQHAMFG)in domain Ⅲ ofβ2-glycoprotein I.β2GPI-reactive CD4^(+)T cells from the two models differed primarily in cytokine production:T cells from mice with induced SLE expressed IFN-γ,while T cells from MRL/lpr mice expressed both IL-17 and IFN-γ,indicating that IL-17-expressing T cells are not necessary for generating aβ2GPI-reactive T cell response.These data suggest that the generation of aβ2-glycoprotein Ireactive T cell response is shared by both induced and spontaneous models of systemic lupus erythematosus and that this T cell response may mediate epitope spread to autoantibodies in both models.

Anti-Aminoacyl tRNA Synthetases Antibodies in Japanese Patients with Interstitial Lung Disease

Objectives: In the present study, we have sought to establish the clinical and immunological characteristics of Japanese patients with interstitial lung disease (ILD). Methods: Serum samples from 35 patients of ILD were screened for autoantibodies using RNA and protein immunoprecipitation assays. Patients with or without serum antibodies to aminoacyl tRNA synthetases (ARS) were assessed clinically and compared. Results: Sera from 12 of 35 (34%) patients with ILD (mean age at onset = 49.7 yrs;range 27 - 65 yrs) were found to contain anti-ARS antibodies (anti-EJ: 3 patients;anti-OJ: 2 patients;anti-PL-12: 3 patients;anti-KS: 4 patients). Nine of the 12 (75%) were female. Six (50%) had Raynaud’s phenomenon, 5 (42%) had arthralgia/arthritis and four (33%) had rheumatoid factor. Lung biopsy specimens of 8 patients with anti-ARS antibodies were examined histologically in detail. The following was determined: Two patients had usual interstitial pneumonia;3 had non-specific interstitial pneumonia;one had organizing pneumonia;one had lymphocyte interstitial pneumonia and the remaining patient had desquamative interstitial pneumonia. Age at disease onset was significantly lower and the frequency of Raynaud’s phenomenon was significantly greater in these patients compared to anti-ARS-negative patients (49.7 yrs vs. 62.6 yrs, p = 0.004;50% vs. 4%, p = 0.003, respectively). Conclusions: These results indicate that the presence of anti-ARS autoantibodies correlates with ILD without definite diagnosis of connective tissue diseases as well as polymyositis/dermatomyositis (PM/DM) with ILD in Japanese patients.

Rheumatology and functional genome analysis in East Asia

Rheumatic diseases differ in severity and outcome across ethnic groups.Although genetic predisposition is an important factor influencing the development of rheumatic diseases,genomic data to date have been accumulated mainly in Europeans.However,East Asia has become an influential center for genetic studies worldwide,and there is also a growing need for a functional genome database for East Asians.Expression quantitative trait locus data for immune cell subsets can be extremely useful in interpreting the function of disease-associated genetic polymorphisms.The development of a functional genome database for East Asians is expected to make a significant contribution to the understanding and stratification of the pathogenesis of rheumatic diseases in this population in the future.

Application of Bioengineered Bacteria in Allergic Diseases

In recent years,increasing attention has been paid to bioengineered bacteria as vectors for the treatment of allergic diseases.The methods for preparing bioengineered bacteria that can express exogenous genes are improving.Research has focused mainly on application of bioengineered bacteria expressing recombinant allergens,hypoallergenic derivatives of allergens,T-cell epitope derivatives,cytokines,or as mucosal adjuvants to enhance immunotherapy effects.This strategy offers new ideas for the treatment of allergic diseases.This review summarizes recent advances in use of live bioengineered bacteria in allergic diseases as well as the challenges of using microorganisms(or their components)in immunotherapy.

Research Progress in Chronic Autoimmune Urticaria

Introduction Urticaria,more commonly known as the sudden development of transient hives(wheals),angioedema,or both,is a prevalent disorder that affects 15%–25%of the general population at some point during their lifetimes.1 The condition tends to be more common in adults than in children,and more common in women than in men with a peak occurrence in the third to fifth decades of life.This condition is marked by the onset of pruritic wheals,which manifest as well-circumscribed areas of nonpitting edema with blanched centers and raised borders that involve only the superficial portions of the dermis and are seen in conjunction with surrounding erythema of the skin.

Elevated Serum Total IgE Levels in Patients with Chronic Urticaria Indicate Insensitivity to Antihistamine Treatment

Objective:Serum total IgE (tlgE) levels are elevated in patients with chronic urticaria (CU);however,the nature of the elevated serum tlgE level in CU patients remains unclear.The aim of this study was to investigate the relationship between elevated serum levels of tlgE in patients with CU and the sensitivity of these patients to antihistamine treatments.Methods:Blood samples of 302 patients with CU were collected,and their levels of serum tlgE were measured.The patients were divided into two groups according to their serum tlgE level:High serum tlgE level group (>150 U/mL)and Low serum tlgE level group (< 150 U/mL).The correlations between the serum tlgE end disease severity as well as the sensitivity of patients to antihistamine treatments were assessed.Data were statistically analyzed using t-tasts and Chi-square tests.Results:Higher rates of positive autologous serum skin test results (X2=5.707,P=0.017) and skin scratch test results (x2 =5.878,P=0.015),higher CU scores (average:2.88±0.73 vs.2.18±0.59,t =6.377,P< 0.001),and longer disease course durations (median:8.5 vs.14.6,z=5.525,P<0.001) were observed in patients with high levels of serum tlgE compared with those with low levels of serum tlgE;moreover,patients with higher levels of serum tlgE were less sensitive to antihistamine therapies compared with those with lower levels of serum tlgE (x2=16.783,P < 0.001).Conclusion:Our study indicates that the high serum tlgE level is associated with the disease severity as well as with low sensitivity to antihistamine treatment of patients.