scholarly journals Systemic anti-commensal response to fungi analyzed by flow cytometry is related to gut mycobiome ecology

Microbiome ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Alicia Moreno-Sabater ◽  
Gaelle Autaa ◽  
Delphine Sterlin ◽  
Amenie Jerbi ◽  
Remy Villette ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Alpha Diversity ◽  
Fungal Species ◽  
Individual Variability ◽  
Humoral Immune ◽  
Healthy Donors ◽  
Significant Difference ◽  
Genus Richness ◽  
Humoral Responses ◽  
The Impact

Abstract Background Interest for the study of gut mycobiota in relation with human health and immune homeostasis has increased in the last years. From this perspective, new tools to study the immune/fungal interface are warranted. Systemic humoral immune responses could reflect the dynamic relationships between gut mycobiota and immunity. Using a novel flow cytometry technology (Fungi-Flow) to determine immunoglobulin (Ig) responses to fungi, we studied the relationships between gut mycobiota and systemic humoral anti-commensal immunity. Results The Fungi-Flow method allows a sensitive and specific measurement of systemic IgG responses against 17 commensal and environmental fungi from the two main divisions; Ascomycota and Basidiomycota. IgG responses exhibited a high inter-individual variability. Anti-commensal IgG responses were contrasted with the relative abundance, alpha-diversity, and intra-genus richness of fungal species in gut mycobiota of twenty healthy donors. Categorization of gut mycobiota composition revealed two differentiated fungal ecosystems. Significant difference of anti-Saccharomyces systemic IgG responses were observed in healthy donors stratified according to the fungal ecosystem colonizing their gut. A positive and significant correlation was observed between the variety of IgG responses against fungal commensals and intestinal alpha-diversity. At the level of intra-genus species richness, intense IgG responses were associated with a low intra-genus richness for known pathobionts, but not commensals. Conclusions Fungi-Flow allows an easy and reliable measure of personalized humoral responses against commensal fungi. Combining sequencing technology with our novel Fungi-Flow immunological method, we propose that there are at least two defined ecosystems in the human gut mycobiome associated with systemic humoral responses. Fungi-Flow opens new opportunities to improve our knowledge about the impact of mycobiota in humoral anti-commensal immunity and homeostasis.

scholarly journals Immunophenotypic Response After Allografting In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3371-3371 ◽  
Author(s):  
Luisa Giaccone ◽  
Lucia Brunello ◽  
Roberto Passera ◽  
Moreno Festuccia ◽  
Milena Gilestro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
First Line ◽  
Significant Difference ◽  
The Impact

Abstract Background Minimal residual disease (MRD) by multiparameter flow-cytometry recently showed a promising role in predicting outcomes in patients with multiple myeloma. However, data on immunophenotypic response (IR) after allografting are lacking. Aim To evaluate the impact of IR and compare it to conventional complete remission (CR) following allografting in myeloma patients. Methods Sixty-six consecutive patients, median age 54 years (35-66), who underwent an allograft between January 2000 and December 2011 with a follow-up of at least 3 months were included. Disease response was evaluated by serum and urine electrophoresis, and bone marrow aspirate at baseline, 3, 6, 12, 18, 24 months after transplant and yearly thereafter. Skeletal survey or MRI were performed yearly or as clinically indicated (overt relapse or complaints of bone pain). Bone marrow aspirates had to contain at least 13000 cells/µL for flow-cytometry studies and IR was defined as absence of monoclonal plasma-cells detected by 4 or 6-colour staining with the following antibodies: CD38, CD138, CD56, CD19, CD45, cyKappa, cyLambda. CR was defined according to standard criteria (Durie et al, Leukemia 2006; 20:1467-73). Results Conditioning regimen was non-myeloablative 2Gy TBI-based in 55 patients, reduced intensity (fludarabine-melphalan-based) in 10 and myeloablative in 1 patient. Post-grafting immunosuppression consisted of cyclosporine with mycophenolate mofetil or methotrexate. Donors were HLA identical siblings in 58 patients and unrelated in 8. Only 1 patient received bone marrow as source of stem cells. Thirty-five/66 (53%) received the allograft as part of the first line treatment, whereas the remaining 31/66, (47%) were transplanted at relapse. At the time of transplant, 5/66 were both in IR and CR, 16 were only in IR and 4 patients were only in clinical CR. All 21 patients in IR at the time of transplant maintained it, while 26/45 (58%) entered IR after the allograft. Among patients surviving at least 3 months, overall treatment related mortality was 10.6% at 3 years. After a median follow-up of 69 months (range 19-147), the incidence of acute and chronic graft-versus-host disease was 45.6% and 49.3% without significant difference between responsive and non-responsive patients. At follow-up, overall, 24 patients achieved CR and IR (CR/IR group), 21 achieved IR but not CR because of persistence of urine/serum M-component (noCR/IR group), and 21 did not achieve either CR or IR (noCR/noIR group). Interestingly, none achieved CR without IR. Median overall survival (OS) and event-free survival (EFS) in patients who achieved IR were 96 and 55 months versus 36 and 7 months in those who did not (p<0.001). Median OS and EFS were not reached and 59 months in the CR/IR group, 77 and 15 months in the noCR/IR, and 30 and 5 months in the noCR/noIR respectively (p<0.001 for both EFS and OS-fig.1). In univariate analysis, being in the CR/IR group was the only significant predictor for prolonged OS and EFS (p<0.001). Of note, cumulative incidence of extra-medullary disease at first relapse after the allograft was 4% in the CR/IR, 32% in the noCR/IR and 15% in the noCR/noIR groups respectively (p<0.001). Receiving the allograft as first line therapy or later during the disease course did not significantly impact on OS and EFS. Conclusion The achievement of IR confers a favorable impact on OS and EFS after allografting. A higher incidence of extra-medullary in the noCR/IR group (some 30% of our patient cohort) may suggest that myeloma cells escape immune control outside the bone marrow. In this group, imaging studies such as positron emission tomography may clinically be indicated during follow-up to detect early relapse. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Impact of Acne Treatment on Skin Bacterial Microbiota: A Systematic Review

2021 ◽  
pp. 120347542110379
Author(s):  
Megan Lam ◽  
Angie Hu ◽  
Patrick Fleming ◽  
Charles W. Lynde
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Flora ◽  
Antimicrobial Properties ◽  
Alpha Diversity ◽  
Individual Variability ◽  
Cochrane Central Register ◽  
Microbiome Composition ◽  
Cutibacterium Acnes ◽  
Acne Treatment ◽  
The Impact

Background Microbial strains such as Cutibacterium acnes have been examined as contributors to the pathogenesis of acne. Given the prevalence of the disease among adolescents and adults, the overutilization of antimicrobial agents may breed resistance and alter commensal microflora. Objectives To characterize the impact of acne treatment on the diversity and relative abundance of the cutaneous microbial community, particularly of the bacterial flora Methods An electronic search was conducted of Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) on June 5, 2020. Interventional and observational studies examining patients receiving acne treatment with culture-independent, community-level analysis of the cutaneous microbiome were included. Results Nine studies with 170 treated acne patients were included. Five studies reported a significant change in alpha diversity following treatment, 3 of which examining systemic antibiotics reported significant increases in diversity. Two of 3 studies examining effects of benzoyl peroxide reported a decrease in diversity. However, trends in diversity were heterogeneous among studies. Conclusions While individual variability in microbiome composition, and study-level heterogeneity in study sampling techniques may limit quantitative synthesis, our results support findings that acne treatment, including those not considered to have antimicrobial properties, alters the composition of the cutaneous microbiome. PROSPERO registration: CRD42020190629

Unique ELISA-Based Assays for VWF-GPIb Interactions and the Impact of Racial Differences on VWF Testing

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 423-423
Author(s):  
Veronica H. Flood ◽  
Patricia A. Morateck ◽  
Pamela A. Christopherson ◽  
Kenneth D. Friedman ◽  
Joan Cox Gill ◽  
...  
Keyword(s):  
Racial Differences ◽  
Von Willebrand Disease ◽  
Mutant Form ◽  
Plasma Samples ◽  
Healthy Donors ◽  
Significant Difference ◽  
The Mean ◽  
Clinical Biology ◽  
Von Willebrand ◽  
The Impact

Abstract Diagnosis of von Willebrand disease (VWD) relies primarily on assays of von Willebrand factor (VWF) function (VWF:RCo) and concentration of VWF protein (VWF:Ag). VWF:RCo is a surrogate measure of VWF activity for VWF interaction with the GPIb receptor on platelets. For VWD screening purposes, some have advocated that VWF:RCo is the most appropriate single test, but variability and reproducibility of VWF:RCo assays between laboratories has been problematic. Alternative assays have therefore been sought. Type 2 VWD variants, 2A, 2B, and 2M, are characterized by a discrepancy between the VWF:Ag and VWF:RCo, yet numerous factors can affect this ratio. Previously, our laboratory has reported a cell based assay to measure VWF interaction with the GPIb complex by flow cytometry, but such assay instrumentation is not available in hemostasis testing laboratories. Plasma samples were collected from 75 healthy donors enrolled in the TS Zimmerman Program for the Molecular and Clinical Biology of VWD, including 44 African American (AA) and 31 Caucasian subjects. VWF:Ag and VWF:RCo levels were performed in a central laboratory, as were collagen binding (VWF:CB) and propeptide (VWFpp) testing. Two ELISA-based assays were developed to measure VWF interaction with GPIb using recombinant GPIbα – one using normal GPIb with ristocetin (VWF:RCo ELISA) and the other a mutant form of GPIbα containing the platelet-type mutations D235Y and M239V that does not require ristocetin (VWF:IbCo ELISA). A monoclonal antibody is used to capture the rGPIb and to orient the GPIb for subsequent interaction with VWF. Serially diluted plasma samples were incubated for 1 hour with or without added ristocetin and monoclonal antibodies to VWF were used to detect the presence of VWF. Both assays utilized a 10 minute agitation at the end of the plasma incubation step. For all subjects, the mean VWF:Ag was 142, the mean VWF:RCo was 124, and the mean VWF:RCo/VWF:Ag ratio was 0.90. The two new assays yielded similar activity results when all the control subjects were analyzed, with a mean of 104 for the VWF:RCo ELISA and a mean of 108 for the VWF:IbCo ELISA. Both assays correlated well with each other and with the VWF:RCo. R squared values as determined by linear regression were 0.79 for the comparison of the VWF:RCo ELISA with the VWF:IbCo ELISA and 0.80 for comparison of either with the regular VWF:RCo. When the results were analyzed by race, however, a significant difference was seen for the two ristocetin-containing assays. The mean VWF:RCo/VWF:Ag ratio for the AA controls was 0.85, compared to 0.95 for the Caucasian controls (p&lt;0.025). For the ristocetin ELISA, the mean was 0.54 for the AA controls and 0.79 for the Caucasian controls (p&lt;0.001). However, no significant racial difference was seen for the VWF:IbCo ELISA with mean of 0.72 for the AA controls and 0.81 for the Caucasian controls (p=NS). Other VWF ratios have been proposed to be used to classify VWD – VWF:CB/VWF:Ag, FVIII/VWF:Ag, and VWFpp/VWF:Ag, but none were significantly different by race. The use of ELISA-based assays to determine VWF function is therefore feasible and may alleviate some of the problems inherent in the traditional VWF:RCo assay, including reproducibility and the technical demands of the assay. The VWF:IbCo assay may also eliminate racial differences in the VWF activity to antigen ratio, thus preventing the potential for erroneous diagnosis of VWD. Furthermore, the ELISA-based assays can be performed using standard hemostasis laboratory instrumentation.

OCT-1 Protein Expression Detected by Flow Cytometry Provided Valuable Information in CML Patients Treated with Imatinib MesylateÃ, FHigher hOCT-1 Expression Predict Better Outcome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1117-1117
Author(s):  
Huanling Zhu ◽  
Qiurong Zhang ◽  
Nenggang Jiang ◽  
Ting Liu
Keyword(s):  
Flow Cytometry ◽  
Protein Expression ◽  
Conflicts Of Interest ◽  
Organic Cation Transporter ◽  
Negative Control ◽  
Expression Level ◽  
Molecular Response ◽  
Fluorescent Intensity ◽  
Healthy Donors ◽  
Significant Difference

Abstract Abstract 1117 Poster Board I-139 Objective The human organic cation transporter-1(hOCT-1) is the major active influx protein responsible for the transport of imatinib into cells. The functional activity of the hOCT-1 protein using 14-C detected by others demonstrated a link between CML molecular response and hOCT-1 activity. However, 14-C labeled detection is not convenient in routine clinical practice. Hence, we use flow cytometry to detect hOCT-1 protein expression level in CML patient and try to find some relation between hOCT-1 expression and imatinib response. Subjects and methods In this study, 64 CML CP patients and 31 healthy donors were enrolled. Totally, there are 78 patient' peripheral blood (PB) or bone marrow (BM) samples and 31 donor PB samples were measured. The hOCT-1 protein expression levels were detected by indirect immunofluorescent flow cytometry. The hOCT-1 levels were expressed as mean fluorescent intensity (MFI). In avoided to systematic error, lymphocytes which had little hOCT-1 expression were used as internal negative control. Results ‡@ Assessing PB hOCT-1 expressing in patients with donors, hOCT-1 level is higher in healthy donors than in CML patient (mean±standard deviation 9.11±6.04,5.60±3.74,P=0.005). ‡AThe hOCT-1 level was compared with molecular response in patients. Of 39 patients achieved optimal molecular response, the hOCT-1 level was 6.49±3.83, versus 3.86±2.91 in 20 patients with non-optimal response(P=0.009). Comparing 39 optimal responders with 16 sub-optimal responders, hOCT-1 level were 6.49±3.83, versus 3.98±1.23(P=0.025. ‡B Assessing CML stages with hOCT-1 expression, there is no significant difference in chronic stage and advanced stage(5.93±3.87, 3.49±1.64, P=0.085). Conclusions hOCT-1 expression level measured by flow cytometry is very convenient and clinically available. The hOCT-1 expression level can be an important predictor in CML patients treated with imatinib mesylate. Disclosures No relevant conflicts of interest to declare.

scholarly journals Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain

Blood ◽  
2009 ◽  
Vol 113 (18) ◽  
pp. 4250-4261 ◽  
Author(s):  
Thaidra Gaufin ◽  
Rajeev Gautam ◽  
Melissa Kasheta ◽  
Ruy Ribeiro ◽  
Erin Ribka ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antibody Production ◽  
Neutralizing Antibody ◽  
Viral Loads ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Significant Difference ◽  
Anti Cd20 ◽  
And Control ◽  
The Impact

AbstractWe investigated the impact of rhesus macaque (RM) B-cell depletion before inoculation with the isolate SIVsmmD215. Seven RMs were treated every 3 weeks with 50 mg/kg of an anti-CD20 antibody (rituximab) starting 7 days before inoculation for 2 (n = 4) and 5 (n = 3) months. Four control animals received no antibody. Three animals were completely depleted of CD20+ B cells, but 4 were only partially depleted of CD20 cells in the LNs and intestine. The decrease in antibody production was consistent with the efficacy of tissue CD20 depletion. Seroconversion and neutralizing antibody production was significantly delayed in animals showing complete tissue CD20 depletion and remained at low titers in all CD20-depleted RMs. Surprisingly, there was no significant difference in acute or chronic viral loads between CD20-depleted and control animal groups. There was a tendency for lower viral set points in CD20-depleted animals. At 6 weeks after inoculation, cellular immune responses were significantly stronger in CD20-depleted animals than in controls. There was no significant difference in survival between CD20-depleted and control animals. Our data suggest that a deficiency of Ab responses did not markedly affect viral replication or disease progression and that they may be compensated by more robust cellular responses.

scholarly journals Assessing the impact of storage time on the stability of stool microbiota richness, diversity, and composition

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Elizabeth A. Holzhausen ◽  
Maria Nikodemova ◽  
Courtney L. Deblois ◽  
Jodi H. Barnet ◽  
Paul E. Peppard ◽  
...  
Keyword(s):  
Community Composition ◽  
Storage Time ◽  
New Technologies ◽  
Alpha Diversity ◽  
Population Based ◽  
Individual Variability ◽  
Storage Duration ◽  
Relative Abundances ◽  
The Impact ◽  
Baseline Sample

Abstract Background New technologies like next-generation sequencing have led to a proliferation of studies investigating the role of the gut microbiome in human health, particularly population-based studies that rely upon participant self-collection of samples. However, the impact of methodological differences in sample shipping, storage, and processing are not well-characterized for these types of studies, especially when transit times may exceed 24 h. The aim of this study was to experimentally assess microbiota stability in stool samples stored at 4 °C for durations of 6, 24, 48, 72, and 96 h with no additives to better understand effects of variable shipping times in population-based studies. These data were compared to a baseline sample that was immediately stored at − 80 °C after stool production. Results Compared to the baseline sample, we found that the alpha-diversity metrics Shannon’s and Inverse Simpson’s had excellent intra-class correlations (ICC) for all storage durations. Chao1 richness had good to excellent ICC. We found that the relative abundances of bacteria in the phyla Verrucomicrobia, Actinobacteria, and Proteobacteria had excellent ICC with baseline for all storage durations, while Firmicutes and Bacteroidetes ranged from moderate to good. We interpreted the ICCs as follows: poor: ICC < 0.50, moderate: 0.50 < ICC < 0.75, good: 0.75 < ICC < 0.90, and excellent: ICC > 0.90. Using the Bray–Curtis dissimilarity index, we found that the greatest change in community composition occurred between 0 and 24 h of storage, while community composition remained relatively stable for subsequent storage durations. Samples showed strong clustering by individual, indicating that inter-individual variability was greater than the variability associated with storage time. Conclusions The results of this analysis suggest that several measures of alpha diversity, relative abundance, and overall community composition are robust to storage at 4 °C for up to 96 h. We found that the overall community richness was influenced by storage duration in addition to the relative abundances of sequences within the Firmicutes and Bacteroidetes phyla. Finally, we demonstrate that inter-individual variability in microbiota composition was greater than the variability due to changing storage durations.

scholarly journals Study on the Course of Cryptosporidium baileyi Infection in Chickens Treated with interleukin-1 or Indomethacin

1999 ◽  
Vol 47 (2) ◽  
pp. 207-216 ◽  
Author(s):  
S. Hornok ◽  
Z. Széll ◽  
Tatjana A. Shibalova ◽  
I. Varga
Keyword(s):  
Immune Response ◽  
Skin Test ◽  
Humoral Immune Response ◽  
Interleukin 1 ◽  
Immunological Parameters ◽  
Humoral Immune ◽  
Significant Difference ◽  
Humoral Responses ◽  
Cellular Immune ◽  
Cryptosporidium Baileyi

The effects exerted by human recombinant interleukin-1β (hrIL-1β) and the prostaglandin inhibitor indomethacin on the course of Cryptosporidium baileyi infection in chickens were studied. Daily oocyst shedding was monitored by a quantitative method throughout the experiment. Humoral immune response to C. baileyi was assessed by ELISA at 3 weeks of age while the level of cellular immune response to phytohaemagglutinin-P (PHA-P) by a skin test at 23 days of age. Parenteral application of hrIL-1b decreased oocyst shedding to 62%, but the infection ran a similar course in treated and control birds. The PHA-P skin test demonstrated increased cellular immune reaction in chickens receiving IL-1b, but there was no significant difference in the humoral responses of the two groups as detected by ELISA. On the other hand, indomethacin mixed to the feed lessened oocyst shedding to 13.7% and also shortened its duration. Immunological parameters as reflected by PHA-P skin test and ELISA results indicated enhanced cellular but unaltered humoral immune response. These data suggest that the sys- temic application of interleukin-1 can induce partial protection against C. baileyi in chickens and that prolonged, abundant oocyst shedding is due to an indometha- cin-sensitive immunodepression via the prostaglandin pathway.

The impact of gut microbial composition on response to neoadjuvant chemotherapy (NACT) in early-stage triple negative breast cancer (TNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 590-590
Author(s):  
Nour Abuhadra ◽  
Chia-Chi Chang ◽  
Clinton Yam ◽  
Jason B White ◽  
Elizabeth Ravenberg ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Early Stage ◽  
Univariate Analysis ◽  
Alpha Diversity ◽  
Microbial Composition ◽  
Fecal Microbiota Transplant ◽  
Fecal Samples ◽  
Response To Chemotherapy ◽  
Significant Difference ◽  
The Impact

590 Background: The impact of gut microbiome on tumor biology, progression and response to immunotherapy has been shown across cancer types. However, there is little known about the impact of gut microbial composition on response to chemotherapy. We have previously shown that the gut microbiome remains unaltered during NACT in a cohort of 32 patients. Here we investigate the association between gut microbiome and response to NACT in a larger cohort of early-stage TNBC. Methods: Longitudinal fecal samples were collected from 85 patients with newly-diagnosed, early-stage TNBC patients enrolled in the ARTEMIS trial (NCT02276443). Patients all received standard NACT with adriamycin/cyclophosphamide (AC); volumetric change was assessed using ultrasound and patients with < 70% volumetric reduction (VR) after 4 cycles of AC were recommended to receive targeted therapy in addition to standard NACT to improve response rates. We performed 16S sequencing on bacterial genomic DNA extracted from 85 pre-AC fecal samples using the 2x250 bp paired-end read protocol. Quality-filtered sequences were clustered into Operational Taxonomic Units and classified using Mothur method with the Silva database version 138. For differential taxa-based univariate analysis, abundant microbiome taxa at species, genus, family, class, and order levels were analyzed using DESeq2 after logit transformation. Alpha-diversity indices within group categories were calculated using phyloseq. Microbial alpha diversity (within-sample diversity) was measured by Simpson's reciprocal index. β-diversity was measured using weighted UniFrac distances between the groups. The association between microbiota abundance and pathologic complete response (pCR) or residual disease (RD) was assessed using DESeq2 analysis. Results: Pre-AC fecal samples from 85 patients were available for analysis. Amongst them, there were 46 patients with pCR and 39 patients with RD. There was no significant difference in alpha diversity (p = 0.8) or beta-diversity (p = 0.7) between the pCR and RD groups. However, relative to patients with RD, the gut microbiome in patients with pCR was enriched for the Bifidobacterium longum species (p = 0.03). The gut microbiome in patients with RD was enriched for Lachnospiraceae (p = 0.03) at the genus level and the Bacteroides thetaiotaomicron species (p = 0.02). Conclusions: We have demonstrated significant differences in the gut microbial composition in patients with pCR as compared to patients with RD. Further investigation in larger studies is needed to support therapeutic exploration of gut microbiome modulation in TNBC patients receiving chemotherapy such as probiotic supplementation or fecal microbiota transplant.

scholarly journals Effect of Different Disease-Modifying Therapies on Humoral Response to BNT162b2 Vaccine in Sardinian Multiple Sclerosis Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Maristella Pitzalis ◽  
Maria Laura Idda ◽  
Valeria Lodde ◽  
Annalisa Loizedda ◽  
Monia Lobina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Smoking Status ◽  
Humoral Response ◽  
Disease Modifying Therapies ◽  
Significant Difference ◽  
Disease Modifying ◽  
Multiple Sclerosis Patients ◽  
Humoral Responses ◽  
The Impact

ObjectivesVaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients.MethodsWe obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology. Previous SARS-CoV-2 infection was assessed by anti-Nucleocapsid (N) serology. Patients were either untreated or undergoing treatment with a total of 13 different DMTs. Differences between treatment groups comprised of at least 10 patients were assessed by generalized linear mixed-effects model. Demographic and clinical data and smoking status were analyzed as additional factors potentially influencing humoral immunity from COVID-19 vaccine.ResultsMS patients treated with natalizumab, teriflunomide, azathioprine, fingolimod, ocrelizumab, and rituximab showed significantly lower humoral responses compared to untreated patients. We did not observe a statistically significant difference in response between patients treated with the other drugs (dimethyl fumarate, interferon, alemtuzumab and glatiramer acetate) and untreated patients. In addition, older age, male sex and active smoking were significantly associated with lower antibody titers against SARS-CoV-2. MS patients previously infected with SARS-CoV-2 had significantly higher humoral responses to vaccine than uninfected patients.ConclusionHumoral response to BNT162b2 is significantly influenced by the specific DMTs followed by patients, as well as by other factors such as previous SARS-CoV-2 infection, age, sex, and smoking status. These results are important to inform targeted strategies to prevent clinically relevant COVID-19 in MS patients.

scholarly journals Effect of different disease-modifying therapies on humoral response to BNT162b2 vaccine in Sardinian multiple sclerosis patients

2021 ◽  
Author(s):  
Maristella Pitzalis ◽  
Maria Laura Idda ◽  
Valeria Lodde ◽  
Annalisa Loizedda ◽  
Monia Lobina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Smoking Status ◽  
Humoral Response ◽  
Disease Modifying Therapies ◽  
Significant Difference ◽  
Disease Modifying ◽  
Multiple Sclerosis Patients ◽  
Humoral Responses ◽  
The Impact

Objectives: Vaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients. Methods: We obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology. Previous SARS-CoV-2 infection was assessed by anti-Nucleocapsid (N) serology. Patients were either untreated or undergoing treatment with a total of 13 different DMTs. Differences between treatment groups comprised of at least 10 patients were assessed by generalized linear mixed-effects model. Demographic and clinical data and smoking status were analyzed as additional factors potentially influencing humoral immunity from COVID-19 vaccine. Results: MS patients treated with natalizumab, teriflunomide, azathioprine, fingolimod, ocrelizumab, and rituximab showed significantly lower humoral responses compared to untreated patients. We did not observe a statistically significant difference in response between patients treated with the other drugs (dimethyl fumarate, interferon, alemtuzumab and glatiramer acetate) and untreated patients. In addition, older age, male sex and active smoking were significantly associated with lower antibody titers against SARS-CoV-2. MS patients previously infected with SARS-CoV-2 had significantly higher humoral responses to vaccine than uninfected patients. Conclusion: Humoral response to BNT162b2 is significantly influenced by the specific DMTs followed by patients, as well as by other factors such as previous SARS-CoV-2 infection, age, sex, and smoking status. These results are important to inform targeted strategies to prevent clinically relevant COVID-19 in MS patients.

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