Department Of Immunology Research Articles

Jen Gommerman: Leadership is not a one-way street.

Jen Gommerman is a Canada Research Chair in Tissue Specific Immunity, and a professor and newly appointed chair for the Department of Immunology at the University of Toronto. Her lab is interested in the underlying mechanisms of immune dysregulation in autoimmune diseases such as MS, mucosal immunology, and the role of TNF family members in immune cell biology. We spoke to Jen about the importance of authenticity and openness in leadership, and her goals as she begins her tenure as department chair of Immunology.

The use of high-sensitivity cardiac troponin I in assessing cardiac involvement and Disease prognosis in idiopathic inflammatory myopathy

ObjectivesCardiac involvement is one of the most serious complications of idiopathic inflammatory myopathy (IIM) that indicates poor prognosis. However, there is a lack of effective biomarkers for the identification of cardiac involvement and the prediction of prognosis in IIM. Here, we aimed to explore the value of different cardiac biomarkers in IIM patients.MethodsA total of 142 IIM patients in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2019 to October 2022 were included in this study. The clinical characteristics, laboratory tests, treatments and prognosis were recorded. The disease activity was assessed according to the core set measures. The correlations of the serum cardiac biomarkers levels with disease activity were analyzed by the Spearman correlation test. Risk factors for cardiac involvement were evaluated by multivariate logistic regression analysis.ResultsHigher high-sensitivity cardiac troponin I (hs-cTnI) levels were associated with cardiac involvement (n = 41) in IIM patients [adjusted OR 7.810 (95% CI: 1.962–31.097); p = 0.004], independent of other serum cardiac biomarkers. The abnormal hs-cTnI had the highest AUC for distinguishing of cardiac involvement in IIM patients (AUC = 0.848, 95% CI: 0.772,0.924; p < 0.001). Besides, we found that high serum levels of hs-cTnI were significantly correlated with disease activity. Moreover, patients with higher serum levels of hs-cTnI tended to suffer from poor prognosis.ConclusionsSerum hs-cTnI testing may play a role in screening for cardiac involvement in IIM patients. Abnormal levels of serum hs-cTnI were associated with increased disease activity and poor prognosis.

COVID-19 vaccination hesitancy among patients admitted to the immunology and allergy clinic with drug allergies

The aim of our study was to determine the factors responsible for COVID-19 vaccination acceptance and hesitancy in patients with drug allergies. We prepared a survey to understand the thoughts, hesitancies and experiences about COVID-19 vaccination and COVID-19 infection in patients with drug allergies and statistically examined the results. A survey study was applied to 76 patients who were admitted to Ankara University Internal Medicine Allergy and Immunology Department with drug allergies. 38 patients who were vaccinated and 38 patients who weren’t were compared. Among the 38 patients who were vaccinated, 34 (89.5%) chose Biontech vaccine, 4 (10.5%) chose Sinovac vaccine. Among the patients who weren’t vaccinated, 28 (73.7%) explained they weren’t vaccinatedbecause of drug allergies. Educational statuses were statistically significantly different (p=0.026) among vaccinated and non-vaccinated patients, lower in vaccinated patients. Vaccinated patients thought the vaccine reduced the possibility of COVID-19 infection and complications, which was significantly different (p&lt;0.01). Non-vaccinated group significantly feared the possible allergic reaction to the COVID-19 vaccine, more than the vaccinated group (p=0.028). Fear of the possible side effects of the COVID-19 vaccine (p&lt;0.001) and the thought of the COVID-19 vaccine being associated with unpredictable effects were significantly more evident in the non-vaccinated group (p&lt;0.001). In conclusion, our study analyzed multiple factors in drug allergy patients regarding vaccine acceptance, rejection, and hesitancy for the first time in literature, similar studies with larger samples can also contribute to the literature in the future.

Increasing medical student awareness of pathology through a virtual, asynchronous pathology elective

Faculty from the University of Florida Department of Pathology, Immunology, and Laboratory Medicine developed an asynchronous, fully virtual pathology elective for medical students that emphasizes both foundational pathology concepts as well as the role of pathologists in the broader health system. The program includes ten core modules as well as several selective modules which allows students to tailor their coursework to better align with their desired specialty. After completing each module, students were required to concisely summarize the topic in the form of a 280-character tweet. Students were surveyed immediately after finishing the course and again one year after finishing the course to assess the effectiveness of the course in teaching students about pathology. Survey results showed significant improvement in student knowledge about the field of pathology and high levels of satisfaction with the course content and delivery. The tweet summaries required in the course provided a unique challenge for students. Although the course was initially developed in response to the COVID-19 pandemic, enrollment has continued steadily through 2023. Our study suggests that online pathology electives can be an effective way to increase medical student exposure to pathology and facilitate learning about the field of pathology, especially among students who may not ultimately pursue a career in pathology.

Analysis of Factors Influencing Whole Blood Hydroxychloroquine Concentration in Patients with Systemic Lupus Erythematosus in China.

The aim of this study was to determine the factors associated with the concentrations of hydroxychloroquine (HCQ) and its major metabolite, desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE). Patients with SLE taking oral HCQ for at least 3months were recruited from the Department of Rheumatology and Immunology of Nanjing Drum Tower Hospital. Clinical characteristics and laboratory values were examined. The concentrations of HCQ and DHCQ were measured by high-performance liquid chromatography, and the effects of various factors on the concentrations were investigated. A total of 272 patients were included in this study. The average concentration of HCQ was 690.90ng/ml and the average concentration of DHCQ was 431.84ng/ml. Multivariate analysis indicated that gender (P = 0.015), age (year) (P < 0.001), weight (kg) (P = 0.013), duration of HCQ use (month) (P < 0.001), systemic lupus erythematosus disease activity index (SLEDAI) (P < 0.001), platelet count (× 109/l) (P < 0.001), immunoglobulin G levels (g/l) (P = 0.014) were associated with low HCQ concentrations. Gender (P = 0.006), duration of HCQ use (month) (P < 0.001), SLEDAI (P = 0.007), and platelet count (× 109/l) (P < 0.001) were associated with low DHCQ concentrations. Patients with SLE require long-term administration of HCQ, but blood levels vary widely between individuals. Studying the factors influencing the blood HCQ and DHCQ concentrations and optimizing the dose according to individual characteristics might help to improve the efficacy of HCQ. ChiCTR2300070628.

Related factors of renal injury in primary Sjögren's syndrome

BackgroundPrimary Sjögren’s syndrome (pSS) is a common chronic systemic autoimmune disorder which primarily affects the exocrine glands. Patients may have extraglandular disease involving multiple organs, including the kidneys. This study aimed at investigating the clinical data and laboratory markers which were associated with renal function damage or renal involvement.MethodOne thousand two hundred eighty-eight adult pSS patients from the Department of Rheumatology and Clinical Immunology were enrolled in this retrospective cohort study. And there were 334 patients of them followed up for more than two years for analyzing demographic, clinical data and laboratory markers. Statistical analysis was performed by R software (Version 3.6.2).ResultNearly 95% of 1288 pSS patients were women, and the positive rates of anti-SSA (Sjögren's syndrome A) and anti-SSB were 63% and 27% respectively. 12% of the pSS patients presented renal involvement with eGFR < 60 mL/min/1.73 m2, and the mean age of hospital presentation, serum creatinine and urea were the highest (P < 0.001), and ANA (antinuclear antibody)-positive, anti-SSB-positive and anti-scl-70-positive were more prevalent in this group. Multivariate analyses showed that age, urea, chlorine and anti-SSA indicate a significant association with renal dysfunction. Potassium, sodium and Jo-1 were also confirmed to be related with decreased renal function. The receiver operating characteristic (ROC) analysis including the above factors showed a good performance on the evaluation of renal injury including eGFR < 60 mL/min/1.73 m2 and eGFR 60 -90 mL/min/1.73 m2 in pSS, with area under curve (AUC) values of 0.957 and 0.821, and high sensitivity (71.1% and 84.4%) and specificity (95.5% and 70.5%). After a more than two years follow-up of anti-SSA positive patients, 34.14% of them developed decreased renal function, and 13.58% of them experienced a progression of renal injury with a 23.64% decrease in eGFR.ConclusionAge, urea, chlorine, and anti-SSA were highly associated with renal injury in pSS. Early screening for autoantibodies would be meaningful for evaluation and prevention of renal injury in pSS.

Newly diagnosed ANCA-associated vasculitis after COVID-19 infection: a case report

BackgroundAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic autoimmune disease characterized by mononuclear cell infiltration and small and medium-sized blood vessel destruction leading to renal failure. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to have the potential to induce the presentation or exacerbation of autoimmune disease. This report describes the clinical features of a case of newly diagnosed ANCA-associated vasculitis after COVID-19 Infection.Case presentationDuring the COVID-19 pandemic, a 67- year-old female Japanese was undergoing treatment for interstitial pneumonia, diabetes mellitus, and hypertension at her local doctor. About 2 months ago, she was diagnosed with COVID-19 and went to a hotel for treatment, and her condition improved. But a month later, after her COVID-19 infection, she presented with a fever and cough and visited Yodogawa Christian Hospital in Osaka, Japan. The reverse transcription-polymerase chain reaction was negative. She underwent extensive radiological and laboratory investigations. Serologies revealed a high perinuclear-ANCA titer with a specific anti-myeloperoxidase antibody titer of 31.7 units/mL. We suspected ANCA-associated vasculitis and performed a renal biopsy. Renal biopsy showed evidence of crescentic glomerulonephritis, which was consistent with ANCA-associated vasculitis. The patient was referred to the Department of Rheumatology and Clinical Immunology for steroid pulse and cyclophosphamide treatment.ConclusionsDelayed screening may lead to progression of the autoimmune disease, so prompt diagnosis is necessary. In this case, we could make an immediate diagnosis and refer the patient to the Department of Rheumatology and Clinical Immunology.

Chronic Spontaneous Urticaria in Belgium: Deciphering the Clinical Profile and Treatment of Patients Visiting an Urban City Immunology Department

Background: Chronic urticaria (CSU) is a chronic inflammatory mast cell-driven disorder of which reliable clinical data in Belgium are lacking. This study focusses on clinical characteristics of CSU patients presenting at an urban Immunology-Allergology department. Methods: Outpatients with CSU were included from 2018 to 2021. Clinical characteristics, Dermatology Life Quality Index (DLQI) and Urticaria activity score (UAS7) were collected by thorough anamnesis and questionnaires. Furthermore, patients underwent provocational testing, an autologous serum skin test (ASST) and a blood analysis. Results: The study included 49 CSU patients and 20 non-CSU subjects. CSU was distributed differently with age and sex, showing higher numbers in female patients below the age of 46 years. 67% of CSU patients had accompanying angioedema of which 9% were reported genital. CSU patients scored a mean 8/30 on their DLQI questionnaire. There was no significant difference in immunoglobulin E (IgE), C-reactive protein, and tryptase levels between CSU patients and controls. Oral glucocorticosteroids were prescribed in 23% of CSU patients during their disease course though only half of these patients had a severity grade 4 CSU. In 82% of the included CSU patients, Urticaria Control Test (UCT) scores were below 12. When we hypothetically considered low IgE levels and high IgG anti-thyroid peroxidase levels as differentiation marker for autoimmune (ai)CSU and non-aiCSU, we found that 4% of all included CSU patients could be considered aiCSU. Conclusion: Generally, the inner-city population displayed the same clinical characteristics, as previous cohorts from Northern Europe. The relatively high rate of CSU patients receiving oral glucocorticosteroid treatment for their disease though not always classified as severe, underlines the need to train doctors of various specialties in the treatment algorithms of CSU. Furthermore, by looking at potential autoimmune characteristics, our findings open perspectives on the identification of new routinely used clinical parameters for the detection of aiCSU, a relatively small immunological subtype of CSU.

Seroprevalence of Apparently Healthy and Unvaccinated Healthcare Workers at the Ward of COVID Patients in a Referral Hospital, Dhaka, Bangladesh

Introduction: In Bangladesh, when a SARS-CoV-2 infected person comes to close contact with another person, especially unvaccinated healthcare workers (HCWs) during staying at the hospital, the disease spreads among the other patients also. This study was carried out in the initial stage of the Corona virus disease 2019 (COVID-19) pandemic before the vaccination program had started. It was observed that among the HCWs some were infected by the virus while they take care of the infected patients and some suffered from subclinical infection without significant symptoms whereas some were not infected at all. Objective: To observe the seroprevalence of SARS- CoV-2 antibodies in a specific group of people (HCWs) who were healthy and unvaccinated but exposed to the patients at the COVID ward in a referral hospital. Methods: This study was carried out in Immunology and Virology Department, Armed Forces Institute of Pathology (AFIP), Dhaka Bangladesh from the date of 21st April, 2020 to 31st May, 2020. As this study was carried out in very early stage of the COVID-19 pandemic, samples were collected within a short period that is for forty days only. In this study, 294 samples were collected from apparently healthy and unvaccinated HCWs who work at the COVID wards in a referral hospital. To detect SARS-CoV-2 antibodies, Immunochromatographic (ICT) method was applied which is a well-accepted method worldwide. Results: This study revealed that among 294 samples from healthcare workers, 36% (106) cases developed antibodies but 64% (188) cases didn’t develop any type of antibody and 19.3(57) cases were PCR positive which might be possible due to their duties in COVID ward. Among 106 seroconvert cases, 16.98% (18)were positive for only IgM, 50.9% (54) were positive for only IgG and 34(32.07%)) were positive for both IgG and IgM. Among 57 infected cases, 21.05% (12) were positive for only IgM, 45.61% (26) were positive for only IgG and 33.33% (34) were for both IgG and IgM antibodies. The ratio between male and female in health-workers were 2.58:1 respectively. Conclusion: This study revealed that the serological test of SARS-CoV-2 is useful for the identification of symptomatic, asymptomatic or subclinical infection among the persons who are the close contacts of COVID-19 patients; moreover, it will help to understand the disease outbreak, the contagiousness of SARS- CoV-2 and the immunity to SARS-CoV-2 in both the vulnerable and general populations. JAFMC Bangladesh. Vol 18, No 2 (December) 2022: 31-34

What to Do When Chimeric Antigen Receptor T Cells Are Not the Most Appropriate Option in Second-Line Diffuse Large B Cell Lymphoma: Current Treatment Options for Transplant-Ineligible Patients

This symposium was held on the first day of the 2023 International Conference on Malignant Lymphoma (ICML) Congress in Lugano, Switzerland. Björn Chapuy, a Haematologist in the department of Oncology and Tumour Immunology at Benjamin Franklin Campus, Charité – Universitätsmedizin Berlin, Germany, described the rapid pace of development of new treatment options for patients with diffuse large B cell lymphoma (DLBCL) who relapse after their first-line (1L) of therapy, and introduced an expert panel of speakers including both haematologists and a patient representative from the Lymphoma Coalition, Europe. Philipp Staber, Programme Director for Lymphoma and Chronic Lymphocytic Leukaemia at the Medical University of Vienna, Austria, discussed the importance of tumour boards, and how they are structured, while Natacha Bolaños, Head of membership and alliances for the Lymphoma Coalition Europe, shared insights from a global survey of patients living with DLBCL or relapsed/refractory (R/R) DLBCL. Eva González-Barca, Co-ordinator of the Lymphoma Unit at the Catalan Institute of Oncology, Barcelona, Spain, and Gabriel Brisou, a Haematologist at the Institut Paoli-Calmettes, Marseille, France, presented case studies of patients with R/R DLBCL treated with different therapies at second-line (2L). The panellists also described the supporting data for some of the options for 2L therapy. The overarching message from the symposium was that involvement of the patient, and potentially their caregiver, in treatment decisions is vital, and that recommendations for treatment should come from a multidisciplinary tumour board composed of pathologists, radiologists, and haemato-oncologists, rather than an individual clinician. Though there is currently no simple answer to which treatment approach should be chosen for each patient, the panel hopes that the next few years will bring a greater understanding of the best choices for individualised therapy.

Inborn Errors of Immunity-the Sri Lankan Experience 2010-2022.

Inborn errors of immunity (IEI) are typically monogenic. Data from the Indian subcontinent are relatively scarce. This paper evaluates IEI diagnosed in Sri Lanka. Data of patients diagnosed with IEI from 2010 to 2022 at the Department of Immunology, Medical Research Institute, Colombo, Sri Lanka, were retrospectively analyzed. Two hundred and six patients were diagnosed with IEI, with a prevalence of 0.94per 100,000. The onset of disease was below 12years in 84.9%, whereas in 10.9%, it was after 18years. The male: female ratio was 1.78:1. Consanguinity was identified in 26.6%. IEI were found in all but one (bone marrow failure) of the 10 IUIS categories. Predominantly antibody deficiencies were the most common category among the nine identified (30.1%), followed by combined immune deficiencies with syndromic features (21.3%), immunodeficiencies affecting cellular and humoral immunity (19.9%), congenital defects of phagocyte number or function (13.1%), and defects in intrinsic and innate immunity (8.2%). Severe combined immune deficiency (SCID) was the commonest disease (14.6%), followed by chronic granulomatous disease (CGD) (10.6%) and X linked agammaglobulinemia (8.7%). Of the patients with a known outcome (n = 184), 51 died (27.7%). Mortality rates were high in SCID (83.3%), Omenn syndrome (OS) (100%), and CGD (31.8%) patients. IEI in Sri Lanka are diagnosed mainly in childhood. The low diagnosis rates suggest a need for educating clinicians regarding IEI in adulthood. The high mortality rates associated with some IEI indicate the need of transplant services in the country.

Targeted treatment strategy for patients with severe pulmonary hypertension secondary to connective tissue diseases

AbstractBackgroundPulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTD) (CTD‐PAH) remains a difficult challenge in clinical practice. We aimed to evaluate the effects of targeted vasodilators in patients with severe CTD‐PAH.MethodsThe data of 53 patients with severe CTD‐PAH hospitalized at the Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, were retrospectively reviewed. Patients were followed up for an average of 2 years to track their outcomes. The efficacy of treatment and the survival rate of patients with severe CTD‐PAH were determined.ResultsAmong the causes of severe CTD‐PAH, systemic lupus erythematosus (SLE) was the most common (39.6%), and the age at onset in patients with SLE‐PAH was younger than that of patients with other CTD. Bosentan was more effective than sildenafil in reducing pulmonary artery pressure, improving cardiac function, and increasing survival time. Combination therapy with targeted vasodilators significantly improved the prognosis of patients with severe CTD‐PAH compared with monotherapy.ConclusionsPatients with severe CTD‐PAH should be treated early with targeted vasodilators. In this study, bosentan was superior to sildenafil. Combined treatment might be an option for severe CTD‐PAH.

Increasing the collection flow rate to 2 mL/min is effective and reduces the procedure time in off-line photopheresis.

Extracorporeal photopheresis (ECP) treatment, mostly based on apheresis technology, is used for immunomodulation in various diseases such as cutaneous T-cell lymphoma, graft versus host disease and other (auto)immune disorders. The aim of this study was to collect high cell counts and purity in shorter procedure times using an ECP off-line system with an increased collection flow rate of 2 mL/min to a target volume of 200 mL buffy coat. In this prospective study, data of routinely performed off-line photopheresis treatments were collected and analyzed at the Central Institute for Blood Transfusion & Department of Immunology (ZIB) of the Tirol Kliniken, to assess absolute cell counts and procedure times and to calculate collection efficiencies (CE2). A total of 22 patients participated in this study. The processed blood volume was 4312 mL, the collection time 120 min, overall procedure time 157 min and the absolute cell counts of treated white blood cells (WBC) and mononuclear cells (MNC) were 5.0 and 4.3 × 109 respectively (median values). The calculated CE2 for WBC and MNC was 21.1% and 58.5%, the proportion of treated MNCs of the total number of MNCs present was 55.0%. The data presented in this study show high therapeutically effective cell counts collected with a high MNC purity within a shorter overall collection/procedure time due to an increased collection flow rate.

Circulating natural killer cells and their association with breast cancer and its clinico-pathological characteristics.

Natural killer (NK) cells play a critical role in cancer immunosurveillance and hold promise as both therapies and prognostic markers in advanced disease. We explore factors that may influence NK cell concentration in the peripheral blood of women with breast cancer in Côte d'Ivoire compared to healthy controls and implications for future research in our context. In this cross-sectional case-control study, blood samples were taken from 30 women diagnosed with breast cancer within 6 months of diagnosis and fifteen healthy women at University Teaching Hospital [Centre Hospitalier Universitaire (CHU)] Treichville in Abidjan, Côte d'Ivoire, from March to September 2018. The blood draw could take place at any time following diagnosis and through treatment. Demographic and clinical data were collected. NK cells were isolated, stained, analysed and counted using the flow cytometer at the Department of Immunology at CHU of Cocody. All p-values were two-sided. Mean age among 30 women with breast cancer was 49 years old compared to 45 years old for 15 controls (p = 0.41). Among 30 women with breast cancer, 4 (13.3%) had Stage 2 disease, 14 (46.7 %) at Stage 3, and 12 (40%) at Stage 4. Fourteen (46.7%) had breast cancer that was hormone receptor-positive (HR+) HER2-negative, 10 (33.3%) had triple-negative cancer, three (10.0%) had HR+HER2+ disease, and three (10.0%) HR-HER2+ cancer. NK cell concentration was not associated with cancer diagnosis, age, cancer stage, subtype, or type of treatment patients received (p > 0.05). Although we did not find an association between NK cell concentration, cancer characteristics or treatment, our results be limited by the small sample size and timing of blood draw. Our next steps include a larger study to explore circulating NK cells prior to any treatment and NK cell infiltration within breast cancer tumour and correlating this with response to treatment and prognosis.

Young Investigator Interview with CSCI Distinguished Scientist Awardee Dr. Caroline Quach-Thanh.

Dr. Caroline Quach-Thanh is a Professor in the Departments of Microbiology, Infectious Diseases and Immunology and of Pediatrics at University of Montreal. She is in charge of Infection Prevention and Control at CHU Sainte-Justine where she works as a pediatric infectious diseases specialist and medical microbiologist. Dr. Quach is a clinician-scientist and the Canada Research Chair, Tier 1 in Infection Prevention and Control. In 2022, Dr. Quach-Thanh received the Distinguished Scientist Award 2022 from the Canadian Society for Clinical Investigation. In the same year, she received a Women of Distinction Award-for public service-from the Women's Y Foundation. Dr. Quach-Thanh is the former president from the Association for Medical Microbiology and Infectious Diseases Canada (AMMI), a past Chair of the National Advisory Committee on Immunization (NACI) and is the current chair of the Quebec Immunization Committee. She was named Fellow of the Canadian Academy of Health Sciences and of the Society for Healthcare Epidemiology of America. Dr. QuachThanh was selected as one of the 2019 most Powerful Women in Canada. In 2021, she received the Order of Merit from Université de Montréal and was made Officière de l'Ordre national du Québec in 2022.

P-512 Cell-mediated immunity as a biomarker of predisposition in recurrent miscarriage.

Abstract Study question Are alterations in the peripheral cellular immune system a potential risk factor for recurrent miscarriage? Summary answer Percentage alteration of some circulating immune cell subpopulations could be used as biomarkers or potential therapeutic targets in recurrent miscarriage. What is known already About 50% of patients with recurrent miscarriage (RM) have no known cause of the disease. The maternal immune system plays an important role in maternal-fetal tolerance, so an imbalance in the maternal immune system could trigger reproductive failure in women. Antiphospholipid syndrome is the only immunological alteration with sufficient evidence of association with RM, however, there are many other immunological parameters under investigation that appear to mediate the maternal-fetal relationship such as KIR receptors and HLA-C. Other authors are focusing their studies on reproductive immunology at the cellular level, looking at the role of different lymphocyte subpopulations in RM. Study design, size, duration Prospective observational analytical study (cases and controls) conducted in the Immunology Department of the Hospital General Universitario Gregorio Marañón (Madrid, Spain) from 2019 to 2022. It included a group of 49 non-pregnant women with a clinical history of recurrent miscarriages of unknown cause, and two control groups, one with 40 women of childbearing age who had at least one live newborn and another with 60 women of childbearing age who had no history of pregnancy. Participants/materials, setting, methods The inclusion criteria for the study were: two or more gestational losses (&amp;lt; 22 weeks of pregnancy). Patients with severe uterine pathologies, genetic disorders, thrombophilias, obesity, infections, coeliac disease without gluten restriction, uncontrolled endocrine disorders, immunomodulatory treatment, autoimmune disorders and documented RM were excluded from the study. An immunophenotypic study of T, B, NK and NKT lymphocyte subpopulations and monocytic series was performed. Cell characterization was carried out by 6-colour flow cytometry in peripheral blood. Main results and the role of chance When comparing the cellular profile of RM patients with the profile of both control groups, we observed alterations in the percentage levels of CD3+ T cells, CD8+ T cells, NKT cells and non-switch and class switch memory B cells in the patient group, suggesting the presence of a predominantly pro-inflammatory peripheral cellular immune profile in RM patients. In contrast to previous studies by our research group, we did not observe significant differences between the percentage levels of NK cells and activated CD8+ T cells (HLA DR+) in the patient and control groups, which may be explained by the high and exhaustive patient selection in this study. After association study of these alterations with RM, we identified levels of NKT cells &amp;gt; 5%, CD8+ T cells &amp;gt; 26.50%, non-switch memory B cells &amp;gt; 22% and class switch memory B cells &amp;gt; 32% as new biomarkers of RM risk. In addition, the combination of at least two of these new biomarkers was found to significantly increase the likelihood of developing the disease, suggesting that RM is a complex pathology in which multiple factors may influence the pathogenesis of the disease. Limitations, reasons for caution Among the limitations of our study, we can highlight the collection of control group variables from databases developed in previous studies, in addition to a small sample size. Wider implications of the findings The determination of these immunological biomarkers in RM allows us to evaluate the role of immunomodulatory therapies on these biomarkers in order to evaluate possible new treatments to help prevent immune-mediated reproductive failure, thus contributing to a more personalized medicine. Trial registration number Not applicable

Acute Rejection After Kidney Transplant-An Endpoint Not Predictive of Treatment Effect on Graft Survival.

1 Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois, Chicago, IL. 2 Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL. 3 Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium. 4 Department of Nephrology, UZ Leuven, Leuven, Belgium. Received 21 March 2023. Revision received 13 May 2023. Accepted 17 May 2023. The authors declare no conflicts of interest. W.E.F. participated in data collection, analysis, and writing of the article. M.N. participated in the writing of the article. W.E.F. is a board member for Tutela Pharmaceuticals, Inc., a 501(c)(3) nonprofit, and CTI Clinical Trial Services and is a consultant for Transplant Therapeutics Consortium, Critical Path Institute, and TRACT Therapeutics, Inc. Correspondence: William E. Fitzsimmons, PharmD, MS, University of Illinois, College of Pharmacy, 833 S Wood St, Chicago, IL 60607. ([email protected]).

Nonlinear main components of the cytokine profile in children with community-acquired pneumonia

Cytokines are the key mediators which control and regulate immune and inflammatory responses via complex networks and serve as biomarkers of many diseases. Quantitative determination of cytokines is helpful in assessing immune status and adjusting therapy for various inflammatory diseases, such as sepsis and pneumonia. Since community-acquired pneumonia remains a common cause of childhood morbidity and mortality. At the present stage, prognosis of the disease severity in children is an urgent problem. The aim of our study was to identify associations between cytokine levels in healthy children and in children with community-acquired pneumonia (CAP), depending on the age of patients and severity of the pathological process. The work was carried out at the Department of Microbiology, Virology and Immunology, Department of Propaedeutics of Childhood Diseases and Pediatrics, and at the Research Institute of Immunology at the South Ural State Medical University. The study included 117 children aged 1 to 18 years with radiologically confirmed diagnosis of CAP, either severe or mild degree. The comparison group was composed from 28 healthy children who did not have community-acquired pneumonia, as well as other signs of acute respiratory viral infection at the time of examination, being observed for any chronic disorders. The levels of IL-1β, IFNγ, IL-6, IL-4, IL-10, IL-2, TNFα, IFNλ2 (IL-28A), IFNλ3 (IL-28B), IL-8, MCP-1, IL-17AF, GM-CSF were determined in blood serum by means of ELISA test systems (a “sandwich” technique with peroxidase as an indicator enzyme). For statistical analysis, a multidimensional method was used, i.e., non-linear analysis of the principal components using the CATPCA algorithm. Among the children with CAP, our study revealed a consistent increase of IL-1ß, IL-4, IL-10, IL-2, TNFα, IFNλ2 (IL-28A), IFNλ3 (IL-28B), IL-8, MCP-1, IL-17AF, GM-CSF in blood serum. The highest correlation with severity was shown for IFNλ2 (IL-28A), IFNλ3 (IL-28B) and MCP-1, which may be considered additional biomarkers of the CAP severity. There was also a significant variability of the cytokine profile in healthy children and its significant skewing in pneumonia, especially in severe cases.

Analysis of the clinical characteristics and therapeutic effect of refractory juvenile dermatomyositis to tofacitinib

Objective: To elucidate the clinical features of patients with refractory juvenile dermatomyositis (JDM), and to explore the efficacy and safety of tofacitinib in the treatment of refractory JDM. Methods: A total of 75 JDM patients admitted to the Department of Rheumatology and Immunology in Shenzhen Children's Hospital from January 2012 to January 2021 were retrospectively analyzed, and to analyze the clinical manifestations, efficacy and safety of tofacitinib in the treatment of refractory JDM. Patients were divided into refractory group with using of glucocorticoids in combination with two or more anti-rheumatic drugs for treatment, and the presence of disease activity or steroid dependence after a one-year follow-up. The non-refractory group is defined as clinical symptoms disappeared, laboratory indicators were normal, and clinical remission was achieved after initial treatment, and the clinical manifestations and laboratory indexes of the two groups were compared. The Mann-Whitney U test, Fisher's precision probability test was used for intergroup comparison. Binary Logistic multivariate regression analysis was used to identify risk factors for refractory JDM. Results: Among the 75 children with JDM, 41 were males and 34 were females with a age of onset of 5.3 (2.3, 7.8) years. The refractory group consisted of 27 cases with a age of onset of 4.4 (1.5, 6.8) years, while the non-refractory group consisted of 48 cases with a age of onset of 5.9 (2.5, 8.0) years. Compared with 48 cases in the non-refractory group, the proportion of interstitial lesions and calcinosis in the refractory group was higher than that in the non-refractory group (6 cases (22%) vs. 2 cases (4%), 8 cases (30%) vs. 4 cases (8%), both P<0.05). Binary Logistic regression analysis showed that observation group were more likely to be associated with to interstitial lung disease (OR=6.57, 95%CI 1.22-35.31, P=0.028) and calcinosis (OR=4.63, 95%CI 1.24-17.25, P=0.022). Among the 27 patients in the refractory group, 22 cases were treated with tofacitinib, after treatment with tofacitinib, 15 of 19 cases (86%) children with rashes showed improvement, and 6 cases (27%) with myositis evaluation table score less than 48 score both were improved, 3 of 6 cases (27%) had calcinosis were relieved, and 2 cases (9%) had glucocorticoid-dependence children were successfully weaned off. During the tofacitinib treatment, there was no increase in recurrent infection, blood lipids, liver enzymes, and creatinine were all normal in the 22 cases. Conclusions: Children with JDM with calcinosis and interstitial lung disease are more likely to develop refractory JDM. Tofacitinib is safe and effective for refractory JDM.

Clinical features and prognosis of 118 children with histiocytic necrotizing lymphadenitis

Objective: To explore the clinical features and prognosis of children with histiocytic necrotizing lymphadenitis (HNL). Methods: The clinical data of 118 children with HNL diagnosed and treated in the Department of Rheumatology and Immunology of Children's Hospital, Capital Institute of Pediatrics from January 2014 to December 2021 were retrospectively analyzed. The clinical symptoms, laboratory examination, imaging examination, pathological findings, treatment and follow-up were analyzed. Results: Among the 118 patients, 69 were males and 49 were females. The age of onset was 10.0 (8.0, 12.0) years, ranging from 1.5 to 16.0 years. All the children had fever lymph node enlargement, blood system involvement in 74 cases (62.7%), skin injury in 39 cases (33.1%). The main manifestations of laboratory examination were increased erythrocyte sedimentation rate in 90 cases (76.3%), decreased hemoglobin in 58 cases (49.2%), decreased white blood cells in 54 cases (45.8%) and positive antinuclear antibody in 35 cases (29.7%). Ninety-seven cases (82.2%) underwent B-mode ultrasound of lymph nodes, showing nodular lesions with low echo in the neck; 22 cases (18.6%) underwent cervical X-ray and (or) CT; 7 cases (5.9%) underwent cervical magnetic resonance imaging. Lymph node biopsy was performed in all 118 cases, and the pathological results did not support malignant diseases such as lymphoma or Epstein-Barr virus infection, suggesting HNL. Fifty-seven cases (48.3%) recovered without treatment, 61 cases (51.7%) received oral steroid therapy, and 4 cases (3.4%) received indomethacin as anal stopper. The 118 cases were followed up for 4 (2, 6) years, ranging from 1 to 7 years, 87 cases (73.7%) had one onset and did not develop into other rheumatological diseases, and 24 cases (20.3%) had different degrees of recurrence, 7 cases (5.9%) had multiple system injuries, and all of the tested autoantibodies were positive for medium and high titers. All of them developed into other rheumatic immune diseases, among which 5 cases developed into systemic lupus erythematosus and 2 cases developed into Sjogren's syndrome; 7 cases were given oral steroid therapy, including 6 cases plus immunosuppressant and 2 cases receiving methylprednisolone 20 mg/kg shock therapy. Conclusions: The first-onset HNL portion is self-healing, hormone-sensitive and has a good prognosis. For HNL with repeated disease and multiple system injury, antinuclear antibody titer should be monitored during follow-up, and attention should be paid to the possibility of developing into other rheumatological diseases, with poor prognosis.