Immunoblotting with (sub)class-specific antibodies reveals a high frequency of monoclonal gammopathies in persons thought to be immunodeficient.

Abstract Immunoblotting, in combination with high-resolution electrophoresis and the use of mouse monoclonal antibodies to human (sub)class immunoglobulin (Ig) isotypes, substantially increased the sensitivity with which homogeneous Ig components (H-Ig) could be detected. Using this technique, we reinvestigated 40 selected sera, previously found to be negative for H-Ig by agar electrophoresis and immunofixation, from two groups of individuals thought to have an age-related immunodeficiency, i.e., persons older than 95 years and recipients of kidney grafts who were undergoing immunosuppressive treatment. In both groups, small single or multiple H-Ig components were found, in frequencies of 76% and 79%, respectively. For comparison, the Ig spectrum of 10 sera from patients on dialysis treatment and of 33 sera from young adult blood donors was ordinarily heterogeneous, except for one elderly patient and one blood donor with a previously unknown IgG2 deficiency. These results are complementary to the observations in some immunodeficiencies in children and indicate that the appearance of single or multiple H-Ig components in low concentration can be considered a very sensitive indicator of certain immune system disorders forming a separate category of monoclonal gammopathies.

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A screening for serum markers of arbovirus infections in healthy blood donors from the Volgograd Region

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-2019-5-6-743-749 ◽

2020 ◽

Vol 9 (5-6) ◽

pp. 743-749

Author(s):

A. О. Negodenkoa ◽

D. N. Luchinin ◽

P. Sh. Konovalov ◽

O. A. Pavlyukova ◽

E. A. Skrynnikova ◽

...

Keyword(s):

Blood Serum ◽

Blood Donors ◽

Clinical Signs ◽

Serum Samples ◽

West Nile ◽

Specific Antibodies ◽

Age Related ◽

Tick Borne Encephalitis ◽

Volgograd Region ◽

California Serogroup

Volgograd region is considered to be endemic West Nile fever (WNF) area due to the established circulation of the West Nile virus (WNV) therein. Some previous independent studies examining samples collected on the territory of the Volgograd region revealed markers related to the California serogroup (CSG), Sindbis and Ukuniemi viruses. WNF, CSG, Sindbis and Ukuniemi fever mainly being asymptomatic posing thereby a threat of virus spread due to transfusiological manipulations along with vector-borne transmission are manifested by diverse clinical signs. The study was aimed at detection of antibodies specific to West Nile, tick-borne encephalitis, California serogroup (Tyaginya, Inko), Sidbis, and Ukuniemi viruses in blood donors from the Volgograd region. For this, 404 blood sera samples collected from blood donors residing in the Volgograd as well as the Volgograd region were examined by ELISA. It was found that percentage of blood serum samples positive for arbovirus-specific antibodies was 18.32%. Among the, 67 out of 404 (16.58%) samples contained anti-WNV antibodies, 3 out of 279 (1.08%) samples — to tick-borne encephalitis virus, 1 out of 92 (1.09%) — to California serogroup fever and Ukuniemi viruses, and 2 out of 92 (2.17%) — to Sindbis fever virus. Importantly, the peak number of IgG and IgM WNV-positive samples was found among residents of Volgograd (29 out of 110, 26%) and Oktyabrsky district (7 out of 25, 28%). In addition, anti-Sindbis, Ukuniemi and CSG virus antibodies were detected in blood serum samples from blood donors residing in the Kalachevsky region and the city of Volgograd. Analyzing age-related distribution and percentage of seropositive subjects in each age group showed as follows: the lowest percentage (14.5%) was positive for anti-WNV, Sindbis, Ukuniemi and CSG virus antibodies in blood donors aged 32–41 years, whereas the peak percentage (25%) — in the subjects aged 52–61 years. Thus, virus specific antibodies detected in healthy individuals in the aforementioned region evidence about potential recovery after asymptomatic infections. In this regard, further research is required to determine a role of the such arboviruses in the structure of regional infectious diseases. The data obtained suggest a need to continue serological arbovirus monitoring in the Volgograd region.

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Potential immunotherapy for Alzheimer disease and age-related dementia

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2019.21.1/mischwartz ◽

2019 ◽

Vol 21 (1) ◽

pp. 21-25 ◽

Cited By ~ 1

Keyword(s):

Immune System ◽

Alzheimer Disease ◽

Cross Talk ◽

Immune Checkpoint ◽

Short Review ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

New Approach ◽

Age Related ◽

The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

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Potential immunotherapy for Alzheimer disease and age-related dementia

Dialogues in Clinical Neuroscience ◽

10.31887/dnc.2019.21.1/mschwartz ◽

2019 ◽

Vol 21 (1) ◽

pp. 21-25 ◽

Cited By ~ 1

Keyword(s):

Immune System ◽

Alzheimer Disease ◽

Cross Talk ◽

Immune Checkpoint ◽

Short Review ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

New Approach ◽

Age Related ◽

The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain’s pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain’s disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

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Antibody Therapy for the Control of Viral Diseases: An Update

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190809112704 ◽

2019 ◽

Vol 20 (13) ◽

pp. 1108-1121 ◽

Cited By ~ 7

Author(s):

Miriam Dibo ◽

Eduardo C. Battocchio ◽

Lucas M. dos Santos Souza ◽

Matheus D. Veloso da Silva ◽

Bruna K. Banin-Hirata ◽

...

Keyword(s):

Clinical Trials ◽

Monoclonal Antibodies ◽

Viral Antigen ◽

Viral Infections ◽

Antibody Therapy ◽

Therapeutic Strategies ◽

Viral Diseases ◽

Specific Antibodies ◽

The Status ◽

Epidemiological Impact

The epidemiological impact of viral diseases, combined with the emergence and reemergence of some viruses, and the difficulties in identifying effective therapies, have encouraged several studies to develop new therapeutic strategies for viral infections. In this context, the use of immunotherapy for the treatment of viral diseases is increasing. One of the strategies of immunotherapy is the use of antibodies, particularly the monoclonal antibodies (mAbs) and multi-specific antibodies, which bind directly to the viral antigen and bring about activation of the immune system. With current advancements in science and technology, several such antibodies are being tested, and some are already approved and are undergoing clinical trials. The present work aims to review the status of mAb development for the treatment of viral diseases.

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The Role of Monoclonal Antibodies in Smoldering and Newly Diagnosed Transplant-Eligible Multiple Myeloma

Pharmaceuticals ◽

10.3390/ph13120451 ◽

2020 ◽

Vol 13 (12) ◽

pp. 451

Author(s):

Elena Zamagni ◽

Paola Tacchetti ◽

Paola Deias ◽

Francesca Patriarca

Keyword(s):

Multiple Myeloma ◽

Monoclonal Antibodies ◽

Immune System ◽

Survival Outcomes ◽

Newly Diagnosed ◽

Cellular Targets ◽

Recent Introduction

The recent introduction of monoclonal antibodies (MoAbs), with several cellular targets, such as CD-38 (daratumumab and isatuximab) and SLAM F7 (elotuzumab), differently combined with other classes of agents, has significantly extended the outcomes of patients with multiple myeloma (MM) in different phases of the disease. Initially used in advanced/refractory patients, different MoAbs combination have been introduced in the treatment of newly diagnosed transplant eligible patients (NDTEMM), showing a significant improvement in the depth of the response and in survival outcomes, without a significant price in terms of toxicity. In smoldering MM, MoAbs have been applied, either alone or in combination with other drugs, with the goal of delaying the progression to active MM and restoring the immune system. In this review, we will focus on the main results achieved so far and on the main on-going trials using MoAbs in SMM and NDTEMM.

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Sex dependent differences in physiological ageing in the immune system of lower airways in healthy non-smoking volunteers: study of lymphocyte subsets in bronchoalveolar lavage fluid and blood

Thorax ◽

10.1136/thx.56.6.450 ◽

2001 ◽

Vol 56 (6) ◽

pp. 450-455

Author(s):

E Mund ◽

B Christensson ◽

K Larsson ◽

R Grönneberg

Keyword(s):

Immune System ◽

Bronchoalveolar Lavage ◽

Lymphocyte Subsets ◽

Antigen Expression ◽

Lavage Fluid ◽

Physiological Ageing ◽

Younger Women ◽

Cd8 Cells ◽

Age Related ◽

Surface Antigen Expression

BACKGROUNDAge related changes in the immune system have been studied frequently but a possible relation to sex has not, to our knowledge, previously been examined. The effect of age and sex on the composition of lymphocyte subsets in bronchoalveolar lavage (BAL) fluid and peripheral blood was therefore examined.METHODSBronchoscopy with lavage was performed in 32 healthy non-atopic, non-smoking volunteers (16 women aged 26–63 years (mean 44) and 16 men aged 23–63 years (mean 39)). Cytospin preparations for differential counts of BAL fluid cells and surface antigen expression of lymphocytes from BAL fluid and blood were analysed by flow cytometry.RESULTSMost parameters in the BAL fluid changed with age in women. The percentage of CD4+ lymphocytes increased with age from a mean of 48 (SD10)% in women aged ⩽40 years to 69 (11)% in women aged >43 years (p=0.001). The percentage of CD8+ lymphocytes tended to decrease with age and the CD4/CD8 ratio was 5.8 (1.2) in women aged >43 years compared with 2.1 (0.7) in those aged ⩽40 years (p<0.0001). Women aged >43 years differed from men aged >43 years as well as from younger subjects of both sexes with respect to CD4+ cells and CD4/CD8 ratio, and from younger women with respect to CD8+ cells. There was no age related change in the CD4/CD8 ratio in blood. No sex related differences were seen in the blood or BAL fluid of adults below the age of 40 years.CONCLUSIONSThe composition of lymphocytes with different phenotypes in the lower respiratory tract changes with age in women but not in men. This may have implications for some clinical conditions such as chronic dry cough which are observed predominantly in women.

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Antibodies to Streptococcus pneumoniae Capsular Polysaccharide Enhance Pneumococcal Quorum Sensing

mBio ◽

10.1128/mbio.00176-11 ◽

2011 ◽

Vol 2 (5) ◽

Cited By ~ 22

Author(s):

Masahide Yano ◽

Shruti Gohil ◽

J. Robert Coleman ◽

Catherine Manix ◽

Liise-anne Pirofski

Keyword(s):

Monoclonal Antibodies ◽

Streptococcus Pneumoniae ◽

Quorum Sensing ◽

Direct Effect ◽

Pneumococcal Disease ◽

Effector Cell ◽

Capsular Polysaccharide ◽

Genetic Exchange ◽

Content Type ◽

Specific Antibodies

ABSTRACTThe use of pneumococcal capsular polysaccharide (PPS)-based vaccines has resulted in a substantial reduction in invasive pneumococcal disease. However, much remains to be learned about vaccine-mediated immunity, as seven-valent PPS-protein conjugate vaccine use in children has been associated with nonvaccine serotype replacement and 23-valent vaccine use in adults has not prevented pneumococcal pneumonia. In this report, we demonstrate that certain PPS-specific monoclonal antibodies (MAbs) enhance the transformation frequency of two differentStreptococcus pneumoniaeserotypes. This phenomenon was mediated by PPS-specific MAbs that agglutinate but do not promote opsonic effector cell killing of the homologous serotypeinvitro. Compared to the autoinducer, competence-stimulating peptide (CSP) alone, transcriptional profiling of pneumococcal gene expression after incubation with CSP and one such MAb to the PPS of serotype 3 revealed changes in the expression of competence (com)-related and bacteriocin-like peptide (blp) genes involved in pneumococcal quorum sensing. This MAb was also found to induce a nearly 2-fold increase in CSP2-mediated bacterial killing or fratricide. These observations reveal a novel, direct effect of PPS-binding MAbs on pneumococcal biology that has important implications for antibody immunity to pneumococcus in the pneumococcal vaccine era. Taken together, our data suggest heretofore unsuspected mechanisms by which PPS-specific antibodies could affect genetic exchange and bacterial viability in the absence of host cells.IMPORTANCECurrent thought holds that pneumococcal capsular polysaccharide (PPS)-binding antibodies protect against pneumococcus by inducing effector cell opsonic killing of the homologous serotype. While such antibodies are an important part of how pneumococcal vaccines protect against pneumococcal disease, PPS-specific antibodies that do not exhibit this activity but are highly protective against pneumococcus in mice have been identified. This article examines the effect of nonopsonic PPS-specific monoclonal antibodies (MAbs) on the biology ofStreptococcus pneumoniae. The results showed that in the presence of a competence-stimulating peptide (CSP), such MAbs increase the frequency of pneumococcal transformation. Further studies with one such MAb showed that it altered the expression of genes involved in quorum sensing and increased competence-induced killing or fratricide. These findings reveal a novel, previously unsuspected mechanism by which certain PPS-specific antibodies exert a direct effect on pneumococcal biology that has broad implications for bacterial clearance, genetic exchange, and antibody immunity to pneumococcus.

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Cardiovascular risk in 159 934 frequent blood donors while addressing the healthy donor effect

Heart ◽

10.1136/heartjnl-2018-314138 ◽

2019 ◽

Vol 105 (16) ◽

pp. 1260-1265 ◽

Cited By ~ 1

Author(s):

Karlijn Peffer ◽

Martin den Heijer ◽

Wim L A M de Kort ◽

André L M Verbeek ◽

Femke Atsma

Keyword(s):

Cardiovascular Risk ◽

High Frequency ◽

Healthy Donor ◽

Blood Donors ◽

Cox Regression ◽

Blood Donation ◽

Low Frequency ◽

Sensitivity Analyses ◽

Hospital Data ◽

Dutch Hospital

ObjectiveTo investigate whether regular blood donation decreases cardiovascular risk.MethodsAll 159 934 Dutch whole-blood donors with an active donation career of at least 10 years were categorised into sex-specific donation tertiles based on the number of donations during this 10-year qualification period. Cardiovascular endpoints were based on hospital discharge diagnoses and death certificates from Dutch Hospital Data and Statistics Netherlands and occurring after the 10-year qualification period. Cox regression was used to estimate the age-adjusted and starting year-adjusted hazard rate ratio (HRR).ResultsFemale high-frequency blood donors had a reduced cardiovascular morbidity (HRR=0.91, 95% CI 0.85 to 0.98) compared with low-frequency blood donors. No effect was observed in men (HRR=1.00, 95% CI 0.95 to 1.05). To rule out a residual healthy donor effect (HDE), additional sensitivity analyses using a 5-year qualification period were conducted. The results supported the absence of a residual HDE.ConclusionsThis study showed a protective effect of long-term, high-frequency blood donation against cardiovascular disease. This effect was only observed in women and not in men.

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Decreased Neutrophil Cyclic AMP Response to Isoprenaline Stimulation in the Elderly

Clinical Science ◽

10.1042/cs0650155 ◽

1983 ◽

Vol 65 (2) ◽

pp. 155-157 ◽

Cited By ~ 13

Author(s):

T. G. Cotter ◽

K. O'Malley

Keyword(s):

Monoclonal Antibodies ◽

Cyclic Amp ◽

The Elderly ◽

Population Heterogeneity ◽

Elderly Subjects ◽

Age Related ◽

Significant Difference ◽

Young Subjects ◽

Drug Free

1. Neutrophils from drug-free elderly subjects produced approximately 50% less cyclic AMP in response to isoprenaline than did neutrophils from young subjects. A significant difference in basal cyclic AMP levels was also evident (elderly 2.8 ± 0.37; young 4.9 ± 0.36 pmol of cAMP/107 cells; P < 0.05). 2. With a range of anti-neutrophil monoclonal antibodies no evidence of age-related neutrophil population heterogeneity was found. 3. These findings indicate that the age-related decline in β-adrenoceptor responsiveness is not due to changes in the neutrophil population. 4. The present results support the hypothesis that there is a generalized decline in β-adrenoceptor-mediated responsiveness in the elderly.

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