Low Percentage of Signal Regulatory Protein α/β+ Memory B Cells in Blood Predicts Development of Anti-drug Antibodies (ADA) in Adalimumab-Treated Rheumatoid Arthritis Patients.


:An important goal for personalized treatment is predicting response to a particular therapeutic. A drawback of biological treatment is immunogenicity and the development of antibodies directed against the drug [anti-drug antibodies (ADA)], which are associated with a poorer clinical outcome. Here we set out to identify a predictive biomarker that discriminates rheumatoid arthritis (RA) patients who are more likely to develop ADA in response to adalimumab, a human monoclonal antibody against tumor necrosis factor (TNF)α. By taking advantage of an immune-phenotyping platform, LEGENDScreen™, we measured the expression of 332 cell surface markers on B and T cells in a cross-sectional adalimumab-treated RA patient cohort with a defined ADA response. The analysis revealed seven differentially expressed markers (DEMs) between the ADA+ and ADA- patients. Validation of the DEMs in an independent prospective European cohort of adalimumab treated RA patients, revealed a significant and consistent reduced frequency of signal regulatory protein (SIRP)α/β-expressing memory B cells in ADA+ vs. ADA- RA patients. We also assessed the predictive value of SIRPα/β expression in a longitudinal RA cohort prior to the initiation of adalimumab treatment. We show that a frequency of < 9.4% of SIRPα/β-expressing memory B cells predicts patients that will develop ADA, and consequentially fail to respond to treatment, with a receiver operating characteristic (ROC) area under the curve (AUC) score of 0.92. Thus, measuring the frequency of SIRPα/β-expressing memory B cells in patients prior to adalimumab treatment may be clinically useful to identify a subgroup of active RA subjects who are going to develop an ADA response and not gain substantial clinical benefit from this treatment.


Front Immunol


Frontiers in immunology


Magill L,Adriani M,Berthou V,Chen K,Gleizes A,Hacein-Bey-Abina S,Hincelin-Mery A,Mariette X,Pallardy M,Spindeldreher S,Szely N,Isenberg DA,Manson JJ,Jury EC,Mauri C




Has Abstract


2018-12-05 00:00:00








  • Interaction Between Macrophage Migration Inhibitory Factor and CD74 in Human Immunodeficiency Virus Type I Infected Primary Monocyte-Derived Macrophages Triggers the Production of Proinflammatory Mediators and Enhances Infection of Unactivated CD4+ T Cell

    abstract::Understanding the mechanisms of human immunodeficiency virus type I (HIV-1) pathogenesis would facilitate the identification of new therapeutic targets to control the infection in face of current antiretroviral therapy limitations. CD74 membrane expression is upregulated in HIV-1-infected cells and the magnitude of it...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Trifone C,Salido J,Ruiz MJ,Leng L,Quiroga MF,Salomón H,Bucala R,Ghiglione Y,Turk G

    更新日期:2018-06-27 00:00:00

  • SpBark Suppresses Bacterial Infection by Mediating Hemocyte Phagocytosis in an Invertebrate Model, Scylla paramamosain.

    abstract::Scavenger receptors are cell surface membrane-bound receptors that typically bind multiple ligands and promote the removal of endogenous proteins and pathogens. In this study, we characterized a novel scavenger receptor-like protein, namely, SpBark. SpBark was upregulated in hemocytes after challenges with bacteria, s...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Li XC,Zhou J,Zhou JF,Wang Y,Ma H,Wang Y,Zhao S,Fang WH

    更新日期:2019-08-23 00:00:00

  • Monkeying Around: Using Non-human Primate Models to Study NK Cell Biology in HIV Infections.

    abstract::Natural killer (NK) cells are the major innate effectors primed to eliminate virus-infected and tumor or neoplastic cells. Recent studies also suggest nuances in phenotypic and functional characteristics among NK cell subsets may further permit execution of regulatory and adaptive roles. Animal models, particularly no...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Manickam C,Shah SV,Nohara J,Ferrari G,Reeves RK

    更新日期:2019-05-22 00:00:00

  • Ankylosing Spondylitis: A Trade Off of HLA-B27, ERAP, and Pathogen Interconnections? Focus on Sardinia.

    abstract::The frequency of HLA-B27 in patients with Ankylosing Spondylitis (AS) is over 85%. There are more than 170 recognized HLA-B27 alleles but the majority of them is not sufficiently represented for genetic association studies. So far only two alleles, the HLA-B*2706 in Asia and the HLA-B*2709 in Sardinia, have not been f...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Paladini F,Fiorillo MT,Tedeschi V,Cauli A,Mathieu A,Sorrentino R

    更新日期:2019-01-25 00:00:00

  • Th17 Cells Paradoxical Roles in Melanoma and Potential Application in Immunotherapy.

    abstract::The progressive infiltration of immune cells is associated with the progression of melanoma. Specifically, Th17 cells in melanoma microenvironment have both antitumor and protumor effects. It is now necessary to understand the contradictory data associated with how Th17 cells play a role in melanoma. This review will ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Chen C,Gao FH

    更新日期:2019-02-08 00:00:00

  • Differential Mechanisms of Septic Human Pulmonary Microvascular Endothelial Cell Barrier Dysfunction Depending on the Presence of Neutrophils.

    abstract::Sepsis is characterized by injury of pulmonary microvascular endothelial cells (PMVEC) leading to barrier dysfunction. Multiple mechanisms promote septic PMVEC barrier dysfunction, including interaction with circulating leukocytes and PMVEC apoptotic death. Our previous work demonstrated a strong correlation between s...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Wang L,Mehta S,Ahmed Y,Wallace S,Pape MC,Gill SE

    更新日期:2018-08-02 00:00:00

  • Expression and Roles of Antimicrobial Peptides in Innate Defense of Airway Mucosa: Potential Implication in Cystic Fibrosis.

    abstract::The treatment of respiratory infections is associated with the dissemination of antibiotic resistance in the community and clinical settings. Development of new antibiotics is notoriously costly and slow; therefore, alternative strategies are needed. Antimicrobial peptides (AMPs), the central effector molecules of the...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Geitani R,Moubareck CA,Xu Z,Karam Sarkis D,Touqui L

    更新日期:2020-06-30 00:00:00

  • Characterization of the Porcine CLEC12A and Analysis of Its Expression on Blood Dendritic Cell Subsets.

    abstract::CLEC12A has been proposed as a suitable target for delivering antigen to dendritic cells (DCs) to enhance vaccine efficacy both in human and mouse. In this study, we have characterized the porcine homolog of CLEC12A (poCLEC12A). Using new monoclonal antibodies (mAb), raised against its ectodomain, poCLEC12A was found ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Álvarez B,Nieto-Pelegrín E,Martínez de la Riva P,Toki D,Poderoso T,Revilla C,Uenishi H,Ezquerra A,Domínguez J

    更新日期:2020-05-13 00:00:00

  • Corrigendum: Complement System Inhibition Modulates the Pro-Inflammatory Effects of a Snake Venom Metalloproteinase.

    abstract::[This corrects the article DOI: 10.3389/fimmu.2019.01137.]. ...

    journal_title:Frontiers in immunology

    pub_type: 已发布勘误


    authors: Luchini LSG,Pidde G,Squaiella-Baptistão CC,Tambourgi DV

    更新日期:2019-07-03 00:00:00

  • Leukotriene A4 Hydrolase Is a Candidate Predictive Biomarker for Successful Allergen Immunotherapy.

    abstract:Background:Allergic rhinitis is a common disorder that affects 10% to 40% of the population worldwide. Allergen immunotherapy (AIT) represents the only therapy that has the potential to resolve clinical symptoms of allergic rhinitis. However, up to 30% of patients do not respond to AIT. Biomarkers predicting the clinic...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Ma TT,Cao MD,Yu RL,Shi HY,Yan WJ,Liu JG,Pan C,Sun J,Wei QY,Wang DY,Wei JF,Wang XY,Yin JS

    更新日期:2020-11-24 00:00:00

  • Role of Tumor-Mediated Dendritic Cell Tolerization in Immune Evasion.

    abstract::The vast majority of cancer-related deaths are due to metastasis, a process that requires evasion of the host immune system. In addition, a significant percentage of cancer patients do not benefit from our current immunotherapy arsenal due to either primary or secondary immunotherapy resistance. Importantly, select su...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: DeVito NC,Plebanek MP,Theivanthiran B,Hanks BA

    更新日期:2019-12-10 00:00:00

  • Mass Cytometry Reveals a Sustained Reduction in CD16+ Natural Killer Cells Following Chemotherapy in Colorectal Cancer Patients.

    abstract::The immune system and inflammation plays a significant role in tumour immune evasion enhancing disease progression and reducing survival in colorectal cancer (CRC). Patients with advanced stages of colorectal cancer will all undergo treatment with cytotoxic chemotherapy which may alter the complexity of immune cell po...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Shinko D,McGuire HM,Diakos CI,Pavlakis N,Clarke SJ,Byrne SN,Charles KA

    更新日期:2019-11-05 00:00:00

  • Sex Bias in Asthma Prevalence and Pathogenesis.

    abstract::Sex-related differences in asthma prevalence are well established and change through the reproductive phases of life. As children, boys have increased prevalence of asthma compared to girls. However, as adults, women have increased prevalence of asthma compared to men. Many factors, including genetics, environment, im...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Shah R,Newcomb DC

    更新日期:2018-12-18 00:00:00

  • Systemic Inflammation and Cardiovascular Comorbidity in Psoriasis Patients: Causes and Consequences.

    abstract::Psoriasis is a common inflammatory skin disease characterized by the appearance of red scaly plaques that can affect any part of the body. High prevalence, chronicity, disfiguration, disability, and associated comorbidity make it a challenge for clinicians of multiple specialties. Likewise, its complex pathogenesis, c...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Boehncke WH

    更新日期:2018-04-05 00:00:00

  • Paclitaxel Enhances the Innate Immunity by Promoting NLRP3 Inflammasome Activation in Macrophages.

    abstract::Microtubules play critical roles in regulating the activation of NLRP3 inflammasome and microtubule-destabilizing agents such as colchicine have been shown to suppress the activation of this inflammasome. However, it remains largely unknown whether paclitaxel, a microtubule-stabilizing agent being used in cancer thera...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Zeng QZ,Yang F,Li CG,Xu LH,He XH,Mai FY,Zeng CY,Zhang CC,Zha QB,Ouyang DY

    更新日期:2019-01-29 00:00:00

  • Induction of Mycobacterium Tuberculosis Lipid-Specific T Cell Responses by Pulmonary Delivery of Mycolic Acid-Loaded Polymeric Micellar Nanocarriers.

    abstract::Mycolic acid (MA), a major lipid component of Mycobacterium tuberculosis (Mtb) cell wall, can be presented by the non-polymorphic antigen presenting molecule CD1b to T cells isolated from Mtb-infected individuals. These MA-specific CD1b-restricted T cells are cytotoxic, produce Th1 cytokines, and form memory populatio...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Shang S,Kats D,Cao L,Morgun E,Velluto D,He Y,Xu Q,Wang CR,Scott EA

    更新日期:2018-11-27 00:00:00

  • Environmental Factor-Mediated Transgenerational Inheritance of Igf2r Hypomethylation and Pulmonary Allergic Response via Targeting Dendritic Cells.

    abstract::The developmental origin of allergic diseases has been suggested, but the molecular basis remains enigmatic. Exposure to environmental factors, such as di-(2-ethylhexyl) phthalate (DEHP; a common plasticizer), is suggested to be associated with increased childhood allergic asthma, but the causal relationship and its u...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Suen JL,Wu TT,Li YH,Lee CL,Kuo FC,Yan PS,Wu CF,Tran M,Wang CJ,Hung CH,Wu MT,Chan MWY,Huang SK

    更新日期:2020-12-23 00:00:00

  • Betaine Inhibits Interleukin-1β Production and Release: Potential Mechanisms.

    abstract::Betaine is a critical nutrient for mammal health, and has been found to alleviate inflammation by lowering interleukin (IL)-1β secretion; however, the underlying mechanisms by which betaine inhibits IL-1β secretion remain to be uncovered. In this review, we summarize the current understanding about the mechanisms of b...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Xia Y,Chen S,Zhu G,Huang R,Yin Y,Ren W

    更新日期:2018-11-20 00:00:00

  • Efficacy of Lactoferrin Oral Administration in the Treatment of Anemia and Anemia of Inflammation in Pregnant and Non-pregnant Women: An Interventional Study.

    abstract::The discovery of the ferroportin-hepcidin complex has led to a critical review on the treatment of anemia and anemia of inflammation (AI). Ferroportin, the only known mammalian iron exporter from cells to blood, is negatively regulated by hepcidin, a hormone peptide able to bind to ferroportin, leading to its degradat...

    journal_title:Frontiers in immunology

    pub_type: 临床试验,杂志文章


    authors: Lepanto MS,Rosa L,Cutone A,Conte MP,Paesano R,Valenti P

    更新日期:2018-09-21 00:00:00

  • Role of Viral and Host microRNAs in Immune Regulation of Epstein-Barr Virus-Associated Diseases.

    abstract::Epstein-Barr virus (EBV) is an oncogenic human herpes virus that was discovered in 1964. Viral non-coding RNAs, such as BamHI-A rightward fragment-derived microRNAs (BART miRNAs) or BamHI-H rightward fragment 1-derived miRNAs (BHRF1 miRNA) in EBV-infected cells have been recently reported. Host miRNAs are also upregul...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Iizasa H,Kim H,Kartika AV,Kanehiro Y,Yoshiyama H

    更新日期:2020-03-03 00:00:00

  • Mechanisms of Graft-versus-Host Disease Prevention by Post-transplantation Cyclophosphamide: An Evolving Understanding.

    abstract::Post-transplantation cyclophosphamide (PTCy) has been highly successful at preventing severe acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). The clinical application of this approach was based on extensive studies in major histocompatibility complex (MHC)-m...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Nunes NS,Kanakry CG

    更新日期:2019-11-29 00:00:00

  • Neuroimmunology of Behavioral Comorbidities Associated With Cancer and Cancer Treatments.

    abstract::Behavioral comorbidities (depression, anxiety, fatigue, cognitive disturbances, and neuropathic pain) are prevalent in cancer patients and survivors. These mental and neurological health issues reduce quality-of-life, which is a significant societal concern given the increasing rates of long-term survival after variou...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Santos JC,Pyter LM

    更新日期:2018-06-07 00:00:00

  • CAR Talk: How Cancer-Specific CAR T Cells Can Instruct How to Build CAR T Cells to Cure HIV.

    abstract::Re-directing T cells via chimeric antigen receptors (CARs) was first tested in HIV-infected individuals with limited success, but these pioneering studies laid the groundwork for the clinically successful CD19 CARs that were recently FDA approved. Now there is great interest in revisiting the concept of using CAR-expr...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Kim GB,Hege K,Riley JL

    更新日期:2019-09-27 00:00:00

  • Cyclic Peptide [R4W4] in Improving the Ability of First-Line Antibiotics to Inhibit Mycobacterium tuberculosis Inside in vitro Human Granulomas.

    abstract::Tuberculosis (TB) is currently one of the leading causes of global mortality. Medical non-compliance due to the length of the treatment and antibiotic side effects has led to the emergence of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (M. tb) that are difficult to treat. A current therapeutic stra...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Hernandez J,Ashley D,Cao R,Abrahem R,Nguyen T,To K,Yegiazaryan A,Akinwale David A,Kumar Tiwari R,Venketaraman V

    更新日期:2020-08-13 00:00:00

  • Strategies to Genetically Modulate Dendritic Cells to Potentiate Anti-Tumor Responses in Hematologic Malignancies.

    abstract::Dendritic cell (DC) vaccination has been investigated as a potential strategy to target hematologic malignancies, while generating sustained immunological responses to control potential future relapse. Nonetheless, few clinical trials have shown robust long-term efficacy. It has been suggested that a combination of su...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Cornel AM,van Til NP,Boelens JJ,Nierkens S

    更新日期:2018-05-18 00:00:00

  • Inhibitory Effects of the Lactobacillus rhamnosus GG Effector Protein HM0539 on Inflammatory Response Through the TLR4/MyD88/NF-кB Axis.

    abstract::Inflammatory bowel disease (IBD) is a chronic and relapsing intestinal inflammatory condition with no effective treatment. Probiotics have gained wide attention because of their outstanding advantages in intestinal health issues. In previous studies, a novel soluble protein, HM0539, which is derived from Lactobacillus...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Li Y,Yang S,Lun J,Gao J,Gao X,Gong Z,Wan Y,He X,Cao H

    更新日期:2020-10-05 00:00:00

  • Subclinical Atherosclerosis in Primary Sjögren's Syndrome: Does Inflammation Matter?

    abstract::Sjögren's syndrome (SS) is a systemic autoimmune disease mainly characterized by inflammatory involvement of exocrine gland. Atherosclerosis is a complex process leading to plaque formation in arterial wall with subsequent cardiovascular (CV) events. Recently, numerous studies demonstrated that SS patients bear an inc...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Bartoloni E,Alunno A,Cafaro G,Valentini V,Bistoni O,Bonifacio AF,Gerli R

    更新日期:2019-04-17 00:00:00

  • Emerging Mechanisms of Insulin-Mediated Antiviral Immunity in Drosophila melanogaster.

    abstract::Arboviruses (arthropod-borne viruses), such as Zika (ZIKV), West Nile (WNV), and dengue (DENV) virus, include some of the most significant global health risks to human populations. The steady increase in the number of cases is of great concern due to the debilitating diseases associated with each viral infection. Beca...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Trammell CE,Goodman AG

    更新日期:2019-12-20 00:00:00

  • MicroRNA-1 Negatively Regulates Peripheral NK Cell Function via Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Signaling Pathways During PPRV Infection.

    abstract::Peste des petits ruminants virus (PPRV) has emerged as a significant threat to the productivity of small ruminants worldwide. PPRV is lymphotropic in nature and induces in the hosts a transient but severe immunosuppression, especially innate immunity. However, it remains largely unknown how NK cells respond and are re...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Qi X,Li Z,Li H,Wang T,Zhang Y,Wang J

    更新日期:2020-01-23 00:00:00

  • Alum Activates the Bovine NLRP3 Inflammasome.

    abstract::There has been a move away from vaccines composed of whole or inactivated antigens toward subunit-based vaccines, which although safe, provide less immunological protection. As a result, the use of adjuvants to enhance and direct adaptive immune responses has become the focus of much targeted bovine vaccine research. ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Harte C,Gorman AL,McCluskey S,Carty M,Bowie AG,Scott CJ,Meade KG,Lavelle EC

    更新日期:2017-11-09 00:00:00