Journal Of Immunology Research Articles

As-needed fluticasone furoate for allergic rhinitis appears beneficial

Use of fluticasone furoate nasal spray on an as-needed basis for patients with moderate-to-severe, persistent perennial allergic rhinitis yielded similar improvements in nasal symptoms compared with scheduled once daily use, according to findings of a recent randomized controlled trial. “These results may not apply to other nasal steroids,” said Leslie Hendeles, PharmD, professor emeritus from the College of Pharmacy at the University of Florida, Gainesville. Fluticasone furoate (i.e., OTC Flonase Sensimist Allergy Relief—Glaxo-SmithKline) has greater affinity for the glucocorticoid receptor and has a longer duration of effect than fluticasone propionate (e.g., Flonase Allergy Relief nasal spray and various generic store names). In asthma, for example, Hendeles said that fluticasone furoate is more effective than placebo with once daily administration, whereas fluticasone propionate is no more effective than placebo when given once a day. Fluticasone propionate requires daily dosing twice a day. Allergic rhinitis is a common condition affecting nearly 50% of children and 40% of adults worldwide. Current guidelines for the management of patients with allergic rhinitis recommend the daily use of intranasal corticosteroids. However, previous data have suggested that intermittent or as-needed use of an intranasal corticosteroid may be an effective option for those with seasonal allergic rhinitis. This idea of as-needed use of therapies follows the most recent asthma guideline update. In December 2020, the National Asthma Education and Prevention Program (NAEPP) Coordinating Committee released a focused update to its 2007 asthma guidelines. One of the biggest changes is that NAEPP now recommends that patients aged 12 years and older with mild persistent asthma use low-dose inhaled corticosteroids either once daily or as needed along with a short-acting beta-agonist. Authors of the new study, published in the Journal of Allergy and Clinical Immunology: In Practice, conducted a single-blinded, randomized controlled trial with 108 adults who had moderate-to-severe, persistent perennial allergic rhinitis. The goal was to evaluate the efficacy of as-needed use compared with daily use of fluticasone furoate nasal spray (27.5 mcg/spray). In the as-needed group, patients ad-ministered two sprays once daily for 1 week, followed by as-needed use for 5 additional weeks. In the daily group, patients used two sprays once daily for 6 weeks. Study participants were instructed to record their 24-hour reflective nasal symptoms, such as congestion, rhinorrhea, sneezing, and itching, on a daily diary card using a 4-point rating scale from 0 (no symptoms) to 3 (severe, and sufficiently troublesome to interfere with normal daily activity or sleep). The summation of the four individual nasal symptoms comprised the total nasal symptom score (TNSS). After 6 weeks, researchers found that the mean change in the TNSS from baseline was not significantly different between the two groups from the first week to the sixth week. When assessing individual symptom scores, although the daily group showed more improvement in nasal congestion and sneezing at week 6, there was no difference in nasal itching and rhinorrhea between the groups. Both groups showed similar improvements in quality-of-life scores and the as-needed group used about half as much steroid as the daily cumulative group. Adverse events were comparable in both groups. This new research supports the use of as-needed fluticasone furoate for the management of moderate-to-severe, persistent perennial allergic rhinitis as a reasonable alternative to daily corticosteroids. Since adherence is often an issue with regularly scheduled use of intranasal corticosteroids for allergic rhinitis, the concept of as-needed use may be appealing to both patients and providers as a safe and effective treatment option. Additional studies are needed to confirm the efficacy of other intranasal corticosteroids used on an as-needed basis for those with moderate-to-severe, persistent perennial allergic rhinitis.

6th European Congress of Immunology, 1-4 September 2021, Virtual meeting.

Abstracts of ECI 2021: 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. John Wiley and Sons; 2021. p. 351. (European Journal of Immunology; Vol. 52; No. S1)

One year of Young EFIS: achievements and future directions

One year of Young EFIS: achievements and future directions

The Day of Immunology 2021

The Day of Immunology 2021

Jacob B. Natvig (1934‐2021), one of the founders of Scandinavian Journal of Immunology

Jacob B. Natvig (1934‐2021), one of the founders of Scandinavian Journal of Immunology

«Å ALLTID VILLE NOE – En beretning om immunologiprofessor Jacob Birger Natvigs liv og virke» by Per E.Hem, 283 pages, 2021. www.kolofon.no ISBN: 978‐82‐300‐2181‐1

English title freely translated: ‘The energetic doer—A biography of the professor in immunology Jacob B. Natvig’ This Norwegian biography about Jacob B. Natvig is an interesting story of his life and adventure over 86 years. The book has been authored by Per E. Hem who has a track record of writing biographies of prominent Norwegian politicians and community builders. Natvig, one of the true pioneers in immunology in Scandinavia, died peacefully in his home on 2 April 2021, about the time when this book was published. Not only was Natvig a well-respected scientist but also a person with an inspiring and dedicated personality. The book gives the background of his career where Natvig already in the 1970s became a well-respected scientist in immunology. Further, it presents the story of one of the lasting legacies of Scandinavian immunology when Natvig together with Morten Harboe founded the Scandinavian Journal of Immunology in 1972, with Scandinavian collaborators Gunnar Bendixen, Olli Mäkelä and Hans Wigzell. The establishment of the journal was at the very right moment when immunology rapidly developed. In 1989, Natvig was elected president of the International Union of the Immunological Societies (IUIS) where he made a major effort for immunology in the developing countries. Natvig has been ambitious, but not really followed a strait career path. Rather, his dedication was that ‘the road was developed while walking’. In 1966, he did his postdoc with one of the world’s most famous immunologists—Henry G. Kunkel—at the Rockefeller Institute of Medical Research in New York. This close collaboration had a major impact on Natvig’s future career in immunology at a high international level. When he arrived back to Norway in 1967, he became chief physician and the first head of the newly developed research institute of immunology and rheumatology (IGRI) at the National Hospital in Oslo, at that time only 32 years old. His subsequent career involved also an 8-year period as director of the National Hospital between 1978 and 1986, a period characterized as very demanding but exciting regarding development in several medical fields. After this, he went back to science and then as professor of immunology at the University of Oslo. This biography about Jakob Natvig is an outstanding story of an immensely energetic and engaged person, and dedicated representative for the entire field of immunology in a global perspective. In all, we can follow his career as one of the key pioneers of immunology and clinical immunology in Scandinavia. The value of his dedicated international engagement should not be underestimated, not the least within the IUIS. All in all, he was not only a dedicated leader and an inspirer but also a warm-hearted personality with a passion for his work and field. The book can be highly recommended for those who master one of the Scandinavian languages. It is easy to read and should also be of interest not only for immunologists.

Morten Harboe (1929‐2021), one of the founders of Scandinavian Journal of Immunology

Morten Harboe (1929‐2021), one of the founders of Scandinavian Journal of Immunology

Role models that shaped Scandinavian immunology

Three of Scandinavian immunology's major influencers in the last century (to use modern terminology), Morten Harboe, Jakob B. Natvig and Eric Thorsby, died earlier this year. Three obituaries in this issue of the Scandinavian Journal of Immunology give appreciations of their achievements. The articles provide inspiring recollections of the scientific accomplishments​ of these immunologists, resulting from fascination of then unsolved and mysterious features of immune reactions of humoral and cellular nature. The immunology field has advanced tremendously in the last 50 years. This becomes clear when reading about the questions posed at the start of Harboe's, Natvig's and Thorsby's respective careers. The complexities of the immune system were only starting to be defined back then and in comparison with today, the questions that were asked were much more fundamental in dealing with the overall function of cells and soluble factors. A sense of nostalgia sneaks in, accompanied by a wish to have been part of these early days when we were less concerned by details and more with conceptual problems. However, nostalgia should not be overrated. It is easy to look at the questions asked then in the light of today's methodology and knowledge. In these days, we did not have FACS, we could not sequence and clone genes and the techniques to produce monoclonal antibodies had not been invented. Thus, while exciting conceptually, these time were also frustrating, encompassing complex cellular assays for immune function and indirect results that had to be interpreted cautiously. The complexity of cellular assays remains today, but the possibility and ease by which big unbiased data sets can be generated increases demands ​of definitive conclusions in seminars and in publications. Because of this, we are less inclined to ask, and even less to answer, big fundamental questions, and it is impossible to publish a papers attempting to attack a question broader than what your combination of molecular and cellular assay can manage. I am sure that in the long run, the advancement of science will benefit from all detail that are now provided, but with regard to being a scientist, we have to be careful not to lose the big picture in the ocean of available descriptive data. Major questions regarding the function of immunity as a whole remain, not the least in vivo. The next generation immunologists need to be stimulated by mentors that ask naïve questions, put things into perspective and stimulate creative thinking. This brings me back to the three giants in immunology who recently passed. They all took their roles as mentors very seriously, supervising younger scientists along their whole careers, stimulating them with broad questions that triggered curiosity. Equally important, they also took a broader responsibility for the development of the field, including founding and leading international societies, chairing departments, organizing conferences, and, not the least pivotal, founding and supporting scientific journals such as the Scandinavian Journal of Immunology.1 It is very important to recognize these legacies from our predecessors in times when the efforts, resources and engagements it takes by us as scientists to fulfil reviewer's and journal's demands for detail is overwhelming. We must not forget our roles as ambassadeurs for our discipline, a role that increases by increasing seniority. Harboe, Natvig and Thorsby were role models in this respect. By following suit, we take responsibility for future generations and for the development of our discipline.

Anca Catrina 1971–2021

Our dear friend and colleague professor Anca Catrina passed away February 8, 2021 due to cancer. Anca Catrina was one of those scientists who made life and science more interesting and challenging for all who had the fortune to meet her. Anca was born in Bucharest, Romania. After medical studies at the University of Bucharest, beginning her practical training as physician, she soon became fascinated by the complexity and the unresolved questions in the field of rheumatology. In order to address both patients’ needs and to begin her scientific career, she shared her time between rheumatology specialist training in Bucharest and research training at Karolinska Institutet, Stockholm, Sweden, where she produced an outstanding thesis on rheumatoid arthritis (RA) in 2004. Soon thereafter, still in Stockholm, she established herself as a group leader in rheumatology research and as a clinician and developed a research line devoted to the understanding of the origins and effects of immunity associated with rheumatic diseases, in particular RA. Based on her conviction that effective therapy is good, but prevention better, she entered into a long and successful research program exploring the basis for the triggering of autoimmunity in RA. She performed pioneering work that increased our understanding of how external agents affecting the lungs may trigger immunity against post-translationally modified, in particular citrullinated antigens. Thus, together with several of her students, clinicians and basic scientists, she showed how citrullination [1], as well as antibody production against citrullinated antigens, may be increased in the lungs of patients with early RA [2, 3]. She also initiated a very promising research line exploring how immunity triggered in lungs may subsequently target cells in the joint giving rise to symptoms seen also in patients with emerging RA [4, 5]. In parallel with this basic work, she organised clinical studies with cohorts of patients at risk for RA to understand disease development [6], but also to use results from the basic studies for clinical trials testing preventive strategies for RA. It must also be emphasized how Anca's charisma and engagement in her fellow scientists as well as her patients made all who met her a bit more happy, a bit more energetic. She had that ability to see and respect everyone, irrespective of background and status. In the midst of all this work, after being appointed professor and head of academic rheumatology at Karolinska, and after having received much international praise and funding, for example a recent ERC grant and the position as an Executive Committee member of the European Journal of Immunology, she was struck by her disease. Typically for Anca, her passion for science and her support to students and to her many national and international collaborators, she remained active in science until the month before her death. The research group and larger scientific environment that she formed is now continuing the work that Anca was only able to start, but her visions of the power of science in improving health and enhancing international collaboration continues to inspire us and many of her friends and colleagues over the world.

JAK inhibitors: Ten years after.

The European Journal of Immunology was launched 50 years ago, coinciding with the discovery of many cytokines and growth factors and the emergence of an entirely new field of research. Ultimately, our knowledge about the biological activity of these factors allowed us to better understand how the immune system functions in the context of inflammatory and autoimmune diseases leading to the development of targeted biologic therapies. The study of cytokine signal transduction led to the discovery of Janus kinases (JAK), and the consideration of therapeutically targeting JAKs to treat immune and inflammatory diseases. This year also marks the tenth anniversary of the approval of the first JAK inhibitor (jakinib) and now there are a total of nine approved jakinibs for treatment of rheumatologic, dermatologic, gastrointestinal, and neoplastic indications and most recently COVID-19. Here, we summarized the discoveries that led to development of first-generation jakinibs, discussed some of the newer, possibly more selective jakinibs, as well as jakinibs that also target other kinases. We also illustrated the rationale behind the application of these drugs in the treatment of COVID-19 cytokine storm. In this review, we will discuss the clinical success of jakinibs, the gaps in our understanding of their biological activities as well as challenges in regard to their clinical application.

PD-1 blocking antibodies moonlighting as killers.

Therapeutic antibodies that block PD-1-mediated inhibition of T cells have revolutionized cancer therapy. Murine cancer models are an essential tool for testing the efficacy of PD-1 blockers alone or in combination with other treatments. Depending on the isotype of the antibody and the host species, blocking antibodies can also exert cytotoxic activity towards cells expressing the target molecule. In the current issue of the European Journal of Immunology [Eur. J. Immunol. 2021. 51: 1473-1481], Polesso etal. demonstrate that depletion of PD-1+ T cells by "blocking" PD-1 antibodies can greatly impact the outcome of preclinical immunotherapy experiments. Whereas some PD-1 antibodies promoted activation and proliferation of PD-1-expressing murine T cells, the authors report that administration of a particular PD-1 antibody can result in a significant loss of antigen-specific CD8 T cells in different in vivo models. These findings once more highlight that a comprehensive characterization of antibodies is warranted to avoid misinterpretation of immunotherapy studies.

Association between septal deviation and OSA diagnoses: a nationwide 9-year follow-up cohort study.

Obstructive sleep apnea (OSA) is a multilevel problematic disease. Major septal deviation (SD) can lead to severe nasal congestion, which, in turn, can lead to sleep apnea. Although SD seems to be related to OSA, very few studies have quantitatively examined this relationship. In this study, we investigate this using a 9-year large-scale cohort study. The SD group was selected out of 1 million individuals randomly extracted by the National Health Insurance Service. The non-SD group was obtained through propensity score matching considering several variables. The primary end point was OSA diagnosis. The study (SD) group included 11,238 individuals and the non-SD group (control group) included 22,476 persons. The overall hazard ratio for OSA in the SD group was 4.39 (95% confidence interval [CI]: 3.56-5.42). In subgroup analysis, the hazard ratio for OSA of male individuals was 3.77 (95% CI: 2.83-5.03), high economic status was 1.27 (95% CI: 1.05-1.56), metropolitan area was 1.31 (95% CI: 1.07-1.62), young age was 0.79 (95% CI: 0.64-0.98), hypertension was 1.00 (95% CI: 0.37-2.7), and diabetes mellitus was 2.44 (95% CI: 1.15-5.21). In the SD group, the hazard ratio for OSA after septoplasty was 0.71 (95% CI: 0.54-0.94). From long-term follow-up, the prevalence of OSA was 4.39 times higher in the SD group compared with the control group. This phenomenon was more pronounced with increasing body mass index and decreased significantly after septoplasty. Yeom SW, Chung SK, Lee EJ, etal. Association between septal deviation and OSA diagnoses: a nationwide 9-year follow-up cohort study. J Clin Sleep Med. 2021;17(10):2099-2106.

MiR-148a weaves its thread into the plasma cell fate.

The plasma cells (PC) are characterized by their rarity, their formidable capacity to continuously secrete massive amounts of antibodies and the potential to live through the whole life span of the organism that houses them. Because of the potency of their effector function, their differentiation and survival are tightly regulated. The PC identity is implemented and maintained by a transcriptional program that allow them to face the challenges entailed by their longevity and high metabolic activity. The main transcription factors overseeing this transcriptional network have been identified (BLIMP1, IRF4, XBP1), but new players, like miRNA, continue to emerge and bring new layers of complexity to the regulatory loops. In the current issue of the European Journal of Immunology [Eur. J. Immunol. 2021. 51: 1089-1109], Pracht etal. identify miR-148a as a significant actor of the PC program that favors the differentiation through the inhibition of competitor fates, and supports the survival and fitness of the long-lived PC. In this commentary, we will discuss the place of miR-148a in the PC transcriptional network and its potential as a therapeutic target in PC-driven diseases.

Editorial introductions.

Editorial introductions.

ECI 2021 goes virtual

ECI 2021 goes virtual

Relationship between body mass index and atopic dermatitis: a Mendelian randomization approach in exploring causality: a critical appraisal.

Atopic dermatitis (AD) is a common, chronic inflammatory skin disease with a complex etiology including genetic and environmental risk factors.1 Obesity has been associated with increased AD risk and severity,2 but a causal relationship has not been established. In the Journal of Allergy and Clinical Immunology, Budu-Aggrey et al.3 assessed the causality between elevated body mass index (BMI) and AD using a Mendelian randomization (MR)approach1 .

An early experience of Itolizumab with best supportive care in the treatment of moderate to severe COVID-19 patients: A retrospective study

An early experience of Itolizumab with best supportive care in the treatment of moderate to severe COVID-19 patients: A retrospective study - IJIRM- Print ISSN No: - 2581-4214 Online ISSN No:- 2581-4222 Article DOI No:- 10.18231/j.ijirm.2021.005, IP Indian Journal of Immunology and Respiratory Medicine-IP Indian J Immu

Itolizumab in addressing symptoms of acute respiratory distress syndrome (ARDS) with weaning off oxygen requirements in a COVID-19 patient: A case study

Itolizumab in addressing symptoms of acute respiratory distress syndrome (ARDS) with weaning off oxygen requirements in a COVID-19 patient: A case study - IJIRM- Print ISSN No: - 2581-4214 Online ISSN No:- 2581-4222 Article DOI No:- 10.18231/j.ijirm.2021.013, IP Indian Journal of Immunology and Respiratory Medicine-IP

Cross-sectional study of chest CT-scan findings in patients affected by SARS-CoV-2 in a tertiary care health centre in Guntur Andhra Pradesh

Cross-sectional study of chest CT-scan findings in patients affected by SARS-CoV-2 in a tertiary care health centre in Guntur Andhra Pradesh - IJIRM- Print ISSN No: - 2581-4214 Online ISSN No:- 2581-4222 Article DOI No:- 10.18231/j.ijirm.2021.012, IP Indian Journal of Immunology and Respiratory Medicine-IP Indian J Imm

Cross - sectional study of baseline characteristics, clinical features and biomarkers in patients affected by SARS-CoV-2 in a tertiary care health center in Guntur, Andhra Pradesh

Cross - sectional study of baseline characteristics, clinical features and biomarkers in patients affected by SARS-CoV-2 in a tertiary care health center in Guntur, Andhra Pradesh - IJIRM- Print ISSN No: - 2581-4214 Online ISSN No:- 2581-4222 Article DOI No:- 10.18231/j.ijirm.2021.011, IP Indian Journal of Immunology a