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FOCIS 2025 Virtual Issue

In celebration of the Federation of Clinical Immunology Societies (FOCIS) Annual Meeting in Boston, June 24 – 27 2025, we are pleased to share a selection of Clinical & Experimental Immunology research that complements the scientific programme. These papers represent recent advances in fields such as allergy-mechanisms and immuno-oncology.

We hope you enjoy this collection of articles, and encourage you to share this with colleagues, using the hashtag #FOCIS2025 and tagging @CEIjournal and @FOCISimmunology on X, or @ceijournal.bsky.social and @focisimmunology.bsky.social on Bluesky.

Allergy Mechanisms to Treatments

The role of neutrophils in allergic disease

James Trayer, Johana Isaza-Correa, Lynne Kelly, Maeve Kelleher, Jonathan Hourihane, Aideen Byrne and Eleanor Molloy.

Clinical and Experimental Immunology, Volume 219, Issue 1, 2025, uxae126, https://doi.org/10.1093/cei/uxae126

Neutrophils play a potential amplifying role in food and drug allergy. Neutrophilic inflammation drives a discrete phenotype of treatment-resistant and often severe asthma. Neutrophil dysfunction is a feature of atopic dermatitis contributing to skin flora dysbiosis.


Extracellular distribution of galectin-10 in the esophageal mucosa of patients with eosinophilic esophagitis

Sofie Albinsson, Christine Lingblom, Leif Johansson, Helen Larsson and Christine Wennerås.

Clinical and Experimental Immunology, Volume 212, Issue 2, May 2023, Pages 147–155, https://doi.org/10.1093/cei/uxad026

CD16+ eosinophils and large amounts of extracellular vesicles containing galectin-10, a T-cell suppressive eosinophil protein, were found in the esophageal mucosa of patients with active eosinophilic esophagitis. Both the CD16+ eosinophils and the released galectin-10-containing extracellular vesicles disappeared in successfully treated patients but remained in the mucosa of the non-responders to treatment.


Increased thromboinflammatory load in hereditary angioedema

Olav Rogde Gramstad, Camilla Schjalm, Tom Eirik Mollnes and Erik Waage Nielsen.

Clinical and Experimental Immunology, Volume 214, Issue 2, November 2023, Pages 170–181, https://doi.org/10.1093/cei/uxad091

C1 inhibitor (C1Inh) is a serine protease inhibitor involved in the kallikrein-kinin system, the complement system, the coagulation system, and the fibrinolytic system.


Microbiome and Immunity

Revolutionizing immune research with organoid-based co-culture and chip systems

Diana Papp, Tamas Korcsmaros and Isabelle Hautefort

Clinical and Experimental Immunology, Volume 218, Issue 1, October 2024, Pages 40–54, https://doi.org/10.1093/cei/uxae004

Potential use and translational applications of patient-derived organoids are very diverse. Such models have revolutionized research in immunological diseases. Co-culture of organoids and immune cells can be used to model diseases, test genetic and environmental factors, and screen drugs or compounds with health-promoting or homeostasis-restoring potentials.


Immune cell composition and inflammatory profile of human peri-implantitis and periodontitis lesions

Sebastian Malmqvist, Reuben Clark, Gunnar Johannsen, Annsofi Johannsen, Elisabeth A Boström and Ronaldo Lira-Junior.

Clinical and Experimental Immunology, Volume 217, Issue 2, August 2024, Pages 173–182, https://doi.org/10.1093/cei/uxae033

Peri-implantitis (PI) and periodontitis (PD) are common oral inflammatory diseases. Here we explored the immune cell composition and the corresponding inflammatory profile in soft tissues and crevicular fluid of PI and PD lesions. We found an incremental increase in the proportion of B cells from non-diseased to PI tissues, as well as an enhanced inflammatory profile in PI.

Human cytomegalovirus seropositivity and its influence on oral rotavirus vaccine immunogenicity: a specific concern for HIV-exposed-uninfected infants

Natasha Laban, Samuel Bosomprah, Roma Chilengi, Michelo Simuyandi, Caroline Chisenga, Harriet Ng’ombe, Kalo Musukuma-Chifulo and Martin Goodier.

Clinical and Experimental Immunology, Volume 217, Issue 1, July 2024, Pages 99–108, https://doi.org/10.1093/cei/uxae029

Among rotavirus vaccinated infants, there was no evidence of an association between HCMV-IgM serostatus at 9 months with RV-IgA titer at 12 months (GMR 1.01, 95%CI: 0.70, 1.45; P  = 0.976). However, HIV-exposed-uninfected infants who were HCMV-IgM seropositive at 9 months old had a 63% reduction in RV-IgA geometric mean titers at 12 months compared to HIV-exposed-uninfected infants who were HCMV-IgM seronegative (geometric mean ratio 0.37, 95%CI: 0.17, 0.77; P  = 0.008). 


Plenary Sessions

Tumor gene signatures that correlate with release of extracellular vesicles shape the immune landscape in head and neck squamous cell carcinoma

Isabella Kallinger, Dominique S Rubenich, Alicja Głuszko, Aditi Kulkarni, Gerrit Spanier, Steffen Spoerl, Juergen Taxis, Hendrik Poeck, Mirosław J Szczepański, Tobias Ettl, Torsten E Reichert, Johannes K Meier, Elizandra Braganhol, Robert L Ferris, Theresa L Whiteside and Nils Ludwig.

Clinical and Experimental Immunology, Volume 213, Issue 1, July 2023, Pages 102–113, https://doi.org/10.1093/cei/uxad019

The expression of vesiculation-related genes (EVsig) is upregulated in HNSCC and is associated with a specific immune cell landscape. Hereby, the EVsig correlates with a decreased abundance of tumor-infiltrating effector lymphocytes and with the expression of immunosuppressive markers NT5E and TGBF1.


What do we know about co-stimulatory and co-inhibitory immune checkpoint signals in ankylosing spondylitis?

Christian Schütz and Xenofon Baraliakos.

Clinical and Experimental Immunology, Volume 213, Issue 3, September 2023, Pages 288–300, https://doi.org/10.1093/cei/uxad032

In this review, we summarize the experimental and genetic data available and evaluate the relevance of immune checkpoint signalling in the pathogenesis of ankylosing spondylitis. Markers such as PD-1 and CTLA-4 have been extensively studied and facilitate the concept of an impaired negative immune regulation in ankylosing spondylitis. Other markers are either neglected completely or insufficiently examined, and the data are conflicting. Still, some of those markers remain interesting targets to decipher the pathogenesis of ankylosing spondylitis and to develop new treatment strategies.


Altered CD226/TIGIT expressions were associated with NK phenotypes in primary antiphospholipid syndrome and affected by IL-4/JAK pathway

Yan Long, Ke-Jia Lu, Chang-Sheng Xia, Jing-Hong Feng, Wen-Yi Li, Yin-Ting Ma, Yuan-Yuan Sun, Chun-Hong Fan and Chun Li.

Clinical and Experimental Immunology, Volume 216, Issue 2, May 2024, Pages 132–145, https://doi.org/10.1093/cei/uxae016

Levels of CD56bright NK and natural killer (NK)-like cells were significantly elevated with imbalanced expressions of CD226 and T-cell immunoreceptor with Ig and ITIM domains (TIGIT), exhibited as higher expression of CD226 but lower expression of TIGIT. Imbalanced expression of CD226 and TIGIT were closely associated with activated phenotypes and stronger functions of NK subsets, and this imbalance was most prominently in pAPS patients with complicated serum antiphospholipid antibodies status. Altered CD226/TIGIT expression on CD56bright NK and NK-like cells may be aggravated by stimulation of IL-4 and recovered by JAK inhibitor tofacitinib.


Exposure to gestational diabetes mellitus increases subclinical inflammation mediated in part by obesity

Andrea Musumeci, Colm John McElwain, Samprikta Manna, Fergus McCarthy and Cathal McCarthy.

Clinical and Experimental Immunology, Volume 216, Issue 3, June 2024, Pages 280–292, https://doi.org/10.1093/cei/uxae010

Gestational diabetes mellitus (GDM) is a frequent and serious complication of pregnancy, often associated with obesity. In this study, there was significant evidence of subclinical inflammation in maternal circulation and in both placental and visceral adipose


Immuno-oncology

Efficacy of anti-programmed cell death protein 1 monoclonal antibody combined with bevacizumab and/or Pseudomonas aeruginosa injection in transplanted tumor of mouse forestomach carcinoma cell gastric cancer in mice and its mechanism in regulating tumor immune microenvironment

Xiangyong Liu, Chao Yan, Aijie Yang, Enhao Yu, Jie Yu, Chunyang Zhou, Yun Wang, Kai Wang, Ying Sun and Yufeng Cheng.

Clinical and Experimental Immunology, Volume 213, Issue 3, September 2023, Pages 328–338, https://doi.org/10.1093/cei/uxad069

Anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) combined with bevacizumab and/or Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) has a synergistic effect. Bevacizumab and PA-MSHA can transform the tumor immunosuppressive microenvironment into a supportive immune microenvironment, thus maximizing the antitumor effect of anti-PD-1 mAb.


What do we know about co-stimulatory and co-inhibitory immune checkpoint signals in ankylosing spondylitis?

Christian Schütz and Xenofon Baraliakos.

Clinical and Experimental Immunology, Volume 213, Issue 3, September 2023, Pages 288–300, https://doi.org/10.1093/cei/uxad032

In this review, we summarize the experimental and genetic data available and evaluate the relevance of immune checkpoint signalling in the pathogenesis of ankylosing spondylitis. Markers such as PD-1 and CTLA-4 have been extensively studied and facilitate the concept of an impaired negative immune regulation in ankylosing spondylitis. Other markers are either neglected completely or insufficiently examined, and the data are conflicting. Still, some of those markers remain interesting targets to decipher the pathogenesis of ankylosing spondylitis and to develop new treatment strategies.


Clinical features, diagnosis, and management of pembrolizumab-induced myasthenia gravis

Shaoli Zhao, Yulu Zhou, Wei Sun, Zuojun Li and Chunjiang Wang.

Clinical and Experimental Immunology, Volume 211, Issue 2, February 2023, Pages 85–92, https://doi.org/10.1093/cei/uxac108

Considering an increasing number of reported cases with pembrolizumab induced MG, clinicians need to be more aware of this phenomenon. Pembrolizumab induced MG treatment usually occurs within 8 weeks after administration. The primary treatment for pembrolizumab induced MG is steroids. Other treatments include intravenous immunoglobulin, plasmapheresis, and immunomodulators such as rituximab and cyclosporine


Vaccines, Pathogens & Syndromes

New insights of antineutrophil cytoplasmic antibody-associated vasculitis from the perspective of COVID-19 vaccination

Yang Yang, Yi Xiong and Gaosi Xu.

Clinical and Experimental Immunology, Volume 213, Issue 3, September 2023, Pages 301–309, https://doi.org/10.1093/cei/uxad043

The occurrence of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) has been reported since the coronavirus disease 2019 (COVID-19) vaccination, but whether there is a causal relationship or coincidence remains to be verified. This paper explores the occurrence of AAV, especially in genetically susceptible populations.


Protecting children and adults with primary antibody deficiencies against common and emergent pathogens and non-infectious complications

Olaf Neth, Nizar Mahlaoui and Charlotte Cunningham-Rundles.

Clinical and Experimental Immunology, Volume 218, Issue 2, November 2024, Pages 136–150, https://doi.org/10.1093/cei/uxae059

In this review, the infectious and non-infectious complications of antibody deficiencies will be discussed along with the limited number of studies that support the effective use of the available therapies and to drive the development of new therapies. Some illustrative case studies will be presented and the outlook for additional controlled clinical trials and potential for therapies driven by the underlying disease genetics will be considered.


Conventional and unconventional T-cell responses contribute to the prediction of clinical outcome and causative bacterial pathogen in sepsis patients

Ross J Burton, Loïc Raffray, Linda M Moet, Simone M Cuff, Daniel A White, Sarah E Baker, Bernhard Moser, Valerie B O’Donnell, Peter Ghazal, Matt P Morgan, Andreas Artemiou and Matthias Eberl.

Clinical and Experimental Immunology, Volume 216, Issue 3, June 2024, Pages 293–306, https://doi.org/10.1093/cei/uxae019

This study explores the potential of explainable machine learning models to predict mortality and causative pathogen in sepsis patients and demonstrates the feasibility to identify integrative patterns from clinical parameters, plasma biomarkers, and phenotyping of blood cells. While no single variable had sufficient predictive power, models that combined five and more features were able to predict 90-day mortality after sepsis diagnosis, and discriminate between Gram-positive and Gram-negative bacterial infections. Overall, our findings highlight the added value of measuring the proportion and activation patterns of conventional and unconventional T cells in the blood of sepsis patients in combination with other immunological, biochemical, and clinical parameters.


Metabolic Dysfunction and Inflammation

Regulatory T-cell dysfunction and its implication for cell therapy

Nicolas Valentini, Christopher J Requejo Cier and Caroline Lamarche.

Clinical and Experimental Immunology, Volume 213, Issue 1, July 2023, Pages 40–49, https://doi.org/10.1093/cei/uxad051

Recent advances in Treg-based immunotherapy, as an immune tolerance approach for transplantation and autoimmune diseases, exhibited the need for a better understanding of Treg biology. Classical mechanisms of dysfunction in T cells such as exhaustion, senescence, and anergy are poorly understood in Tregs. Previous works in auto- and alloimmune diseases, as well as in cell-engineering, have shown susceptibility of Tregs to such complications, furthering the importance of this knowledge for future design and interpretation of Treg adoptive immunotherapy trials.


Regulatory T-cell frequency and function in acute myocardial infarction patients and its correlation with ventricular dysfunction

Elena Berenice Martínez-Shio, Laura Sherell Marín-Jáuregui, Alma Celeste Rodríguez-Ortega, Lesly Marsol Doníz-Padilla, Roberto González-Amaro, Carlos David Escobedo-Uribe, Adriana Elizabeth Monsiváis-Urenda.

Clinical and Experimental Immunology, Volume 216, Issue 3, June 2024, Pages 262–271, https://doi.org/10.1093/cei/uxae014

A high percentage of patients with acute coronary syndrome develop heart failure due to the ischemic event. Regulatory T cells play a role in regulating inflammation after an acute myocardial infarction and its function may be compromised in this pathology. This work is the first report to evaluate CD69+ Foxp3− Treg cells in acute myocardial infarction patients.


Immune Dysregulation

Investigating dysregulation of TGF-β1/SMAD3 signaling in atopic dermatitis: a molecular and immunohistochemical analysis

Tabasum Shafi, Roohi Rasool Wani, Showkat Hussain, Imtiyaz A Bhat, Rumana Makhdoomi, Sheikh Adil Bashir, Iffat Hassan, Zafar A Shah. 

Clinical and Experimental Immunology, Volume 216, Issue 2, May 2024, Pages 192–199, https://doi.org/10.1093/cei/uxad130

The study highlights the upregulation of transforming growth factor-β1 (TGF-β1) mRNA and protein expression in the affected skin of patientswith atopic dermatitis (AD), suggesting a potential role for TGF-β1 in the modulation of inflammation and tissue remodeling in AD. The association of TGF-β1 mRNA with vitamin D deficiency in serum, and its protein expression with the severity of AD emphasizes the clinical significance of TGF-β1 in AD pathogenesis and its potential role as a marker for disease severity. A significant decrease in the expression of small mothers against decapentaplegic homolog 3 (SMAD3) in the affected skin of AD patients suggests a dysregulation in the TGF-β1/SMAD3 signaling pathway in AD.


Immune cell activity during anti-TNF treatment in patients with psoriasis and psoriatic arthritis

Aleksandra Petrovic, Victoria Marie Samuelsen, Richard Davies, Anders K Aarebrot, Timothy Holmes, Irene Sarkar, Brith Bergum, Roland Jonsson, Lene F Sandvik, Silje M Solberg and Silke Appel.

Clinical and Experimental Immunology, Volume 218, Issue 3, December 2024, Pages 329–340, https://doi.org/10.1093/cei/uxae070

Psoriasis is a chronic, inflammatory skin disease characterized by a dysregulated immune response and systemic inflammation. Up to one-third of patients with psoriasis have psoriatic arthritis. We here explored the impact of long-term infliximab treatment on the composition and activity status of circulating immune cells involved in chronic skin and joint inflammation.


TREX1 cytosolic DNA degradation correlates with autoimmune disease and cancer immunity

Liwei Fang, Songcheng Ying, Xi Xu and De Wu.

Clinical and Experimental Immunology, Volume 211, Issue 3, March 2023, Pages 193–207, https://doi.org/10.1093/cei/uxad017

The N-terminal domain of Three Prime Repair Exonuclease 1 (TREX1) is catalytically active and can degrade dsDNA or ssDNA in the cytosol, whereas the C-terminal domain is primarily involved in protein localization. TREX1 deficiency induces cytosolic DNA accumulation as well as activation of the cGAS-STING-IFN signaling pathway, which results in tissue inflammation and autoimmune diseases. Furthermore, TREX1 expression in cancer immunity can be adaptively regulated to promote tumor proliferation, making it a promising therapeutic target.