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- Background: Severe Combined Immunodeficiency (SCID) is a category of inborn errors of immunity where there is impaired T and B cell development and/or function. Artemis SCID (Art-SCID) is characterized by dysfunctional Artemis protein, which is crucial for V(D)J recombination in T and B cell maturation. Art-SCID is fatal without management, and current definitive treatment involves hematopoietic stem cell transplantation (HSCT) or gene therapy. As the prognosis and survival of SCID patients improves, current research has begun unveiling long-term complications and morbidities. Previous literature has reported neurodevelopmental abnormalities in SCID patients, such as developmental delay and Autism Spectrum Disorder (ASD). However, it remains unknown whether these neurodevelopmental differences are linked to the SCID mutation, an adverse outcome of treatment and hospitalization, or comorbid social isolation and psychosocial challenges.Aims: In this case series, we discuss two cases of Art-SCID which presented with neurodevelopmental deficits following successful HSCT.Results: In both cases, SCID was detected on Newborn Screening (NBS), and Art-SCID was confirmed with genetic testing. Both patients were successfully treated with HSCT at 80 days of life, and followed up clinically well, with robust cell counts. Both patients later presented in toddlerhood with developmental, speech and language delay, however only one patient met diagnostic criteria for ASD.Conclusion: The definitive relationship between SCID, HSCT, and neurodevelopmental outcomes remain unclear, and warrants further study to allow for early intervention. We are currently working with colleagues across the country to further investigate and define this complex relationship.Statement of Novelty: We are investigating the complex relationship between SCID, HSCT, and potential neurodevelopmental outcomes. We present two cases of patients with Artemis SCID who were successfully treated with HSCT, and later presented in toddlerhood with developmental, speech, and language delay.
- Azhar Al Shaqaq,
- Marina Sham,
- Laura Abrego Fuentes,
- Jenny Garkaby,
- Jessica Willett Pachul,
- Linda Vong,
- Julia Upton,
- Vy Kim, and
- Chaim M. Roifman
Background: The global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been profound, with over 760 million confirmed infections and almost 7 million deaths from coronavirus disease 2019 (COVID-19). The pandemic, officially declared in March 2020, has caused significant and irreversible changes in society. COVID-19 continues to pose a serious threat, ranging from asymptomatic cases to severe outcomes such as acute respiratory distress syndrome and organ failure, putting immense pressure on healthcare systems worldwide. The effects of SARS-CoV-2 infection on individuals with primary immunodeficiency (PID) are not yet fully understood. To date, the available research remains scarce, and the results do not yet provide conclusive evidence of a definitive link between PID and severe SARS-CoV-2 infection. In this study we present the clinical course and outcome of COVID-19 in individuals with PID.Methods: This study is a retrospective analysis involving 65 patients, comprising both pediatric and adult individuals diagnosed with PID, who exhibited symptoms of SARS-CoV-2 infection and tested positive at The Hospital for Sick Children in Toronto, Ontario, Canada. The data was collected from October 2020 to December 2022.Results: Sixty-five patients (36 children and 29 adults) were enrolled in our study. Our patients were diagnosed with primary immunodeficiency, and categorized as combined immunodeficiency, antibody deficiency, immune dysregulation disorder, phagocyte defect, intrinsic and innate immunity, or autoinflammatory disorder. Each of our patients had their COVID-19 infection confirmed through serology, rapid antigen test, and/or PCR. Among the study participants, 24 individuals had pre-existing lung conditions. At the time of contracting the infection, 42 patients had been vaccinated against SARS-CoV-2. The majority of patients in the study experienced mild to moderate symptoms of COVID-19.Conclusion: Our patients with PID exhibited mild to moderate symptoms of COVID-19, and all made a full recovery without any complications.Statement of Novelty: This study sheds light on impact of COVID-19 in individuals with primary immunodeficiency, revealing a noteworthy observation that patients exhibited mild to moderate symptoms, and remarkably, all experienced a complete recovery devoid of complications.- Background: Signal Transducers and Activators of Transcription (STAT) proteins are fundamental for multiple cellular processes, including immunity. STAT5B serves as a signal transducer downstream of cytokine and growth factor-mediated activation. Aberrations in STAT5B are associated with the development of atopy, immunodeficiencies, autoimmunity, cancers, hematological disease, growth disorders, and lung disease. Biallelic STAT5B variants are associated with loss-of-function of the gene, and cause a recessive disorder characterized by growth hormone insensitivity and immune dysregulation. Clinically significant heterozygous variants result in either dominant negative or gain-of-function effects; these latter variants are rare and their impact on the immune system is less clearly delineated than those responsible for the recessive form of the condition.Aim: We describe the presentation, immune workup, and genetic findings in a pediatric patient with a novel STAT5B heterozygous variant.Methods: A thorough retrospective review of the patient’s chart was performed.Results: A four-year-old male presented with history of lymphadenopathy, eczema, asthma, food allergy, short stature, and recurrent upper and lower respiratory tract infections. Clinical trio whole exome sequencing identified a novel heterozygous variant (c.1A>G; p. Met1?) in STAT5B. His mother harbours the same heterozygous variant and has a history remarkable for atopy. Immune investigations on the child revealed persistent elevated IgE. The patient’s variant targets the STAT5B N-terminal domain, and represents the first case with a heterozygous variant affecting this region.Conclusion: We present a novel STAT5B variant associated with a dominantly-inherited growth and immune phenotype. This is the first report of a heterozygous variant affecting the N-terminal domain in association with a clinical phenotype, expanding the genotypic landscape of this disorder. Further investigations and follow up responses to growth hormone replacement are needed to better delineate the functional effect of the variant identified in this family.Statement of Novelty: We report a novel germline heterozygous STAT5B variant in a paediatric patient with lymphadenopathy, atopy, and short stature.
- Background: Neurodevelopment is closely entwined with immune maturation and function during embryogenesis. While haematopoietic-derived microglia have recognized roles in a number of neurodevelopmental processes, the contribution of molecules classically involved in the immune system (including complement, toll-like receptors, and cytokines) are also emerging. To date, approximately 11% of genes known to cause primary immunodeficiency also confer varying degrees of neurological abnormalities. These can range from intellectual disability, cognitive and behavioural disorders, through to seizures, spasticity, and motor development delay. However, very rarely are sensory processing defects associated with aberrations of the immune system.Aims: To define the clinical presentation and immune phenotype of a novel syndrome encompassing immunodeficiency, neurodevelopmental abnormalities, and altered pain sensitivity in two siblings.Methods: Comprehensive retrospective review of the patient’s charts were performed, in accordance with local research ethics board approval.Results: We describe two teenage sisters who presented with recurrent sinopulmonary infections, lymphopenia affecting both B and T cells, developmental delay, learning and processing disorder, seizures, and reduced sensitivity to pain. Other features include bronchogenic cyst, microscopic hematuria, oral ulcers, papular urticaria, and keratosis pilaris.Conclusion: An underlying defect in genes known to cause primary immunodeficiency was not identified, suggesting the role of an as-yet undefined molecule at the crossroads of immunity, neurodevelopment, and sensory processing.Statement of novelty: We report on two patients, siblings, with a novel phenotype of combined immunodeficiency, neurodevelopmental delay, and reduced sensitivity to painful stimuli.
- FREE ACCESSBackground: The cell cytoskeleton is regulated by the ezrin-radixin-moesin (ERM) family of proteins, forming links between transmembrane proteins and the underlying actin cytoskeleton. Phosphorylation and activation of these proteins enable interactions with partners critically involved in shape regulation, such as actin filaments, transmembrane proteins, and scaffolding proteins. The MSN gene encodes moesin, which is ubiquitously expressed in lungs, spleen, kidney, endothelial cells of vessels, lymphocytes, and neutrophils. Deficiency or dysregulation of moesin, called X-linked moesin-associated immunodeficiency (X-MAID), is characterized by severe leukopenia affecting T cells, B cells, and neutrophils. To date, the clinical picture of patients with X-MAID is variable.Aim: We describe the presentation, immune-workup, and lung histopathology findings of a young male patient with X-MAID and multi-organ involvement, whose severe pulmonary vein stenosis necessitated a double lung transplant.Methods: A thorough review of the patient’s chart was performed.Results: The patient presented with a history of recurrent respiratory tract infections, oral thrush, and 3 major bacterial infections requiring admission and antibiotic therapy. His immune evaluation was remarkable for low T cells, and normal numbers of B and NK cells. At age 4 years he underwent a double lung transplant due to severe pulmonary vein stenosis and pulmonary hypertension. He further developed chronic kidney injury post-transplant. Clinical trio whole exome sequencing revealed a novel hemizygous variant in the MSN gene (c.278dupT; p.L93FfsX21), predicted to cause loss-of-function in moesin. Histologic evaluation of the lung tissue before transplantation identified profound abnormalities in alveoli formation.Conclusion: Patients with moesin deficiency may present during infancy or childhood with a severe form of the disease, including combined immunodeficiency with lymphopenia and neutropenia, while adults may have a milder clinical picture. The novel MSN mutation described here adds to the known spectrum of disease and highlights the non-redundant functions of moesin, particularly in the lung.Statement of Novelty: We report the first lung histopathological description of an X-MAID case, in a pediatric patient with recurrent infections, cytopenia, and autoimmunity who underwent a double lung transplant.
- FREE ACCESSBackground: Autoinflammatory diseases are a genetically heterogeneous group of conditions characterized by excessive activation of the innate immune system. They frequently present with overlapping features, particularly in cases of digenic or polygenic inheritance. The most common cause of autoinflammation arises from causative variants in the MEFV gene, responsible for familial Mediterranean fever. Clinical features include recurrent episodes of fever with serositis and amyloidosis. Individuals with variants in MEFV that present atypically with heterogeneous autoinflammatory features have also been described. Notably, gene modifiers of MEFV, such as NOD2 encoding an intracellular bacterial sensor, can result in more severe disease. NOD2 underlies a number of autoinflammatory and immunodeficiency conditions, including Blau syndrome. To date, Blau syndrome has not been described in the context of MEFV.Aim: To expand the presentation and phenotype of autoinflammatory disease associated with defects in the NOD2 and MEFV genes.Methods: A retrospective review of the patient’s chart was performed, including family history, medical history, immune laboratory evaluation, and genetics.Results: We describe here a 68-year-old male with a remarkable medical history since childhood of skin rash, erythroderma, recurrent infections, autoinflammation, arthritis, uveitis, and malignancy. A significant family history of cancer and autoinflammation was noted. Genetic work-up involving a 17-gene autoinflammatory panel revealed 3 heterozygous variants of uncertain significance, 2 of which were present in the MEFV gene and one in the NOD2 gene. His features were consistent with an overlapping phenotype of Blau syndrome and atypical FMF.Conclusion: Heterozygous variants in NOD2 and MEFV can result in a spectrum of autoinflammatory disorders with a heterogeneous phenotype. The NOD2 variant identified in our patient has not previously been associated with Blau syndrome.Statement of Novelty: We describe a patient harbouring heterozygous mutations in the MEFV and NOD2 genes marked by recurrent childhood infections.
- FREE ACCESSBackground: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disease in which cells of the immune system are overactivated, leading to uncontrolled inflammation and tissue destruction. Inherited or familial forms of HLH (FHL) are further classified into FHL1 to 5, based on the underlying genetic etiology. The most common form, FHL2, is associated with mutations in the PRF1 gene encoding perforin, a pore-forming glycoprotein required for natural killer and cytotoxic T cell-mediated apoptosis. Importantly, diagnosis of FHL can be challenging, particularly in late-onset cases in which presentation is delayed beyond the first years of life.Aim: We report the essential role of whole exome sequencing in the diagnostic work-up of a patient with complex, late-onset FHL.Methods: A comprehensive retrospective chart review was performed.Results: Our patient presented at 11 years of age with recurrent fever, hepatosplenomegaly, and pancytopenia. In the following years, she was admitted to hospital on multiple occasions, including twice for febrile neutropenia, and once for febrile cytopenia. Serial immune evaluation revealed features of immune dysregulation. While HLH was suspected, she did not fulfil the diagnostic criteria. Initial genetic work-up involving a targeted primary immunodeficiency gene panel identified only a single novel variant of uncertain significance, c.T374C (p.I125T) in PRF1. Subsequently, research-based whole exome sequencing was performed which revealed a second variant, c.C272T (p.A91V), in the same gene. The expanded genetic findings, a set of compound heterozygous missense mutations in PRF1, strengthened the diagnosis of FHL. She later fulfilled the diagnostic criteria for HLH.Conclusion: Whole exome sequencing identified compound heterozygous mutations in the PRF1 gene in a patient with late-onset FHL.Statement of Novelty: We report the use of whole exome sequencing to identify compound heterozygous mutations in PRF1, including a novel p.I125T variant not previously identified in FHL.
- FREE ACCESSBackground: Polyclonal hypergammaglobulinemia (PHGG) is commonly associated with liver disorders and could signify an enhanced or defective immune system. This study was conducted to determine the distribution and significance of PHGG in phases of chronic hepatitis B infection (CHB).Methods: Serum protein electrophoresis and colorimetric protein were assayed in 80 inactive (IA), 45 immune-clearance (IC) and 17 immune-escape (IE) CHB participants. ANOVA and Student’s t-test were used for the comparison of data, while area under curve analysis was used to assess the performance.Results: A significant elevation in γ-globulin was observed in the 3 phases studied in relation to non-hepatitis B virus-infected controls. The incidence of PHGG in different phases of CHB are IA (61.3%), IC (33.3%), and IE (29.4%). The IA phase, considered the least severe, has the highest incidence of PHGG.Conclusion: Occurrence of PHGG seems to signify enhanced immune responses. It may also be used to some extent to predict the IA phase.Statement of novelty: This study utilized both qualitative and quantitative methods to evaluate the patterns of PHGG in untreated and categorized CHB infections.
- FREE ACCESS
- Jenny Garkaby,
- Ori Scott,
- Laura Abrego Fuentes,
- Linda Vong,
- Jessica Willett Pachul,
- Myra Pereira,
- Vy Hong-Diep Kim, and
- Chaim M. Roifman
Background: Since the onset of the COVID-19 pandemic, a main challenge for clinicians and public health decision-makers has revolved around risk stratification in vulnerable populations, in particular individuals with inborn errors of immunity (IEI). However, available reports of the clinical course of COVID-19 in patients with IEI show wide variability, from a complete lack of symptoms to severe and complicated disease.Objective: To present the clinical features and outcomes of SARS-CoV-2 infection in adult patients with IEI.Methods: We performed a retrospective chart review documenting patient characteristics and clinical course of SARS-CoV-2 infection between December 2021 and July 2022.Results: Ten adult patients with IEI followed in our center were diagnosed with COVID-19, as determined by RT-PCR or rapid antigen testing. IEI in this cohort included those with humoral and combined immunodeficiencies, as well as phagocytic defects. An underlying lung comorbidity was identified in 3 patients. Symptoms were mostly mild and self-limiting, and no severe outcomes, complications, or mortality were noted in this study.Conclusions: We suggest that patients affected by a wide range of both humoral and combined IEI may demonstrate resilience, while highlighting the possible protective effects of vaccination and immunoglobulin replacement in this population.Statement of Novelty: We report on the mild COVID-19 clinical course of 10 adults with IEI. - FREE ACCESSBackground: Yellow Nail Syndrome is defined as a triad of lymphedema, respiratory symptoms, and nail discolouration. The precise etiology remains unknown, however it has been reported alongside a broad spectrum of conditions including malignancies, autoinflammatory diseases, and immunodeficiencies.Aim: To highlight the association between defects in the intracellular bacterial sensor gene NOD2 and Yellow Nail Syndrome.Methods: A retrospective review of the patient’s chart was performed, including family history, characteristics, immune laboratory evaluation, and genetics.Results: A 65-year-old female was referred to our centre for lymphedema and bronchiectasis. She had recurrent episodes of pneumonia, cellulitis, and oral ulcers. Bilateral lymphedema on her lower limbs up to the hip and discoloured yellow nails were reported. Given her clinical picture, she was diagnosed with Yellow Nail Syndrome. The immunological evaluation was unremarkable overall, with normal T cell subsets and function and adequate antibody titers. Genetic testing identified a heterozygous mutation in the NOD2 gene, c.2107C>T (p.Arg703Cys), considered a variant of uncertain significance.Conclusion: Heterozygous variants in NOD2 can result in a spectrum of autoimmune and autoinflammatory disorders, including Yellow Nail Syndrome.Statement of novelty: We describe a patient with Yellow Nail Syndrome, presenting with the classic triad of clinical features. Genetic evaluation identified a heterozygous variant in NOD2, which has been extensively associated with several autoinflammatory diseases, but not Yellow Nail Syndrome.
- FREE ACCESS
- Jenny Garkaby,
- Laura Edith Abrego Fuentes,
- Jessica Willett Pachul,
- Abby Watts-Dickens, and
- Meghan Fraser
Introduction: DiGeorge syndrome is a heterogenous disorder with various clinical presentations. Common features include thymic hypoplasia, T cell lymphopenia, conotruncal heart defects, facial dysmorphism, cleft palate, developmental delay, and hypoparathyroidism. The severity of this condition varies, however typical presentation includes congenital heart defects and characteristic facial features. Isolated hypocalcemia in DiGeorge syndrome is rarely seen in neonates but rather as the sole manifestation in older teenagers or adults.Aim: To report a case of an atypical presentation of DiGeorge syndrome.Results: We report here a case of an infant who was diagnosed with DiGeorge syndrome, with seizures being the only clinical manifestation displayed by the patient. He was found to have low T cell receptor excision circle levels on a newborn screen (NBS) for severe combined immunodeficiency (SCID). He did not have facial dysmorphism nor cardiac defect.Conclusion: Our case shows that severe hypocalcemia can be the only presenting symptom in DiGeorge syndrome. Based on this case, we recommend physicians test for calcium levels and PTH at the first encounter with a patient who screened positive during NBS for SCID.Statement of Novelty: We describe an infant with DiGeorge syndrome who presented with severe hypocalcemia. - OPEN ACCESSIntroduction: The epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), continues to affect most of the world’s population. In children, the respiratory and systemic involvement appears to have a much more benign course in comparison to adults, with almost no fatalities reported. However, we are now encountering a post-infectious immune mediated condition, termed, multisystem inflammatory syndrome in children (MIS-C). In most cases the main features are prolonged fever and elevated inflammatory markers. Many of the patients present with abdominal pain and varying degrees of myocardial involvement, from mild reduction in cardiac output to the most alarming manifestation of cardiovascular shock.Results: We present two patients with unusual manifestations of MIS-C related to post COVID-19 infection: an infant born to a mother who was severely ill at the very end of pregnancy, presenting with prolonged fever, rash, pericardial effusion, and evidence of coronary arteries wall dilation thickening as a result of inflammation, and, a teenage girl with severe cardiac tamponade without the more common cardiac manifestations of myocardial involvement.Discussion: Post COVID-19 MIS-C can present with a wide variety of manifestations. The pathophysiologic mechanisms underlying these inflammatory responses in infants are yet to be elucidated. Physicians should be aware of such presentations since rapid diagnosis and treatment are key for a favourable outcome.Statement of novelty: We present two unique manifestations of post COVID-19 infection which, to date, are not discussed frequently in the literature.
- OPEN ACCESSIntroduction: Common Variable Immune Deficiency (CVID) is the most prevalent form of severe antibody deficiency in children and adults. Most patients suffer recurrent, mainly sinopulmonary, infections. Despite adequate IVIG replacement therapy, chronic lung disease continues to be a main cause of morbidity and mortality. The term granulomatous-lymphocytic interstitial lung disease (GLILD) is frequently used to describe interstitial lung disease associated with immune dysregulation in primary antibody deficiency, such as CVID.Aim: To describe the case of a 10-year-old male with CVID who developed GLILD and his response to treatment with Rituximab.Discussion: Our patient is a young male with CVID and no genetic diagnosis, whose lung functions and general condition continued to deteriorate despite adequate intravenous immunoglobulin replacement therapy and mycophenolate mofetil treatment. After the diagnosis of GLILD, we initiated treatment with a 4-dose weekly course of Rituximab with prompt resolution of his interstitial disease. Although GLILD is a well described condition that accompanies CVID as a manifestation of immune dysregulation, it is still under recognized, especially in the pediatric population. Among experts, there is little uniformity when it comes to diagnostic and treatment approaches. Recent studies showed improved outcomes when using combination therapy with Rituximab, such as in our patient.Statement of Novelty: We shed light on GLILD, an important condition that accompanies CVID, and demonstrate an excellent response to the steroid sparing agent Rituximab. This is a crucial aspect when considering therapeutic choices for the pediatric population.
- OPEN ACCESS
- Adebayo Lawrence Adedeji,
- Dauda Jimoh,
- Jelili Abiodun Badmus,
- Ibrahim Olabanji Bello,
- Ibrahim Eleha Suleiman, and
- Olubunmi Gloria Ayelagbe
Background: Serum protein abnormalities, particularly elevated gamma globulins (hypergammaglobulinemia, HGG), have been reported in apparently healthy Nigerians living in Ogbomoso and elsewhere. Since the mechanisms for this phenomenon have not been fully substantiated, we hypothesized that impaired neutrophil phagocytosis could contribute to this condition.Methods: Healthy humans exhibiting HGG were identified using serum protein electrophoresis performed on cellulose acetate gel in barbital buffer (pH 8.6). GelQuant image analysis and quantitation software were further employed to quantify the gamma globulin fraction. Neutrophils were isolated from K3EDTA anticoagulated peripheral blood using Histopaque neutrophil isolation reagent. Neutrophil phagocytic activity was analyzed using a non-subjective commercial colorimetric phagocytosis assay kit.Results: The purity and viability of isolated neutrophils were approximately 94% and 92%, respectively. Ex-vivo phagocytic activity of neutrophils isolated from apparently healthy subjects exhibiting HGG, expressed as a percentage of the average absorbance of the control group, was 48.1 ± 8.6% which was significantly lower (p < 0.05) compared to the controls (98.9 ± 14.3%).Conclusion: Since neutrophils play crucial roles in innate immune responses, impairment of neutrophil phagocytic activity may lead to persistent antigenic stimulations of the adaptive immune system. This could in turn orchestrate gamma globulins expression leading to HGG.Statement of novelty: We demonstrated reduced neutrophil phagocytic activity as a possible basis for hypergammaglobulinemia in healthy Nigerians, perhaps for the first time. - OPEN ACCESSIntroduction: The impact of SARS-CoV-2 infections in children has generally been described as relatively benign. However, since April 2020, there have been reports of a new multisystem inflammatory illness affecting children and related to COVID-19 termed multisystem inflammatory syndrome in children (MIS-C).Aim: To describe 3 cases of children diagnosed with MIS-C and discuss the disease spectrum.Methods: We collected and reviewed data from 3 cases diagnosed with MIS-C admitted to our pediatric ward between October 2020 and January 2021.Discussion: MIS-C is a newly described disease that spans a spectrum of phenotypes and severity, and while it shares clinical similarities with Kawasaki disease, it has a unique set of epidemiological, laboratory, and prognostic characteristics. In this review, we hope to add to the understanding of this new entity.Statement of Novelty: This report discusses 3 cases of MIS-C and elaborates on the spectrum and immunology of this entity. Our cases are unique in their relatively wide spectrum and variability. We hope our own experience with MIS-C adds to the accumulating knowledge and understanding of this emerging disease.
- OPEN ACCESSBackground: Coronavirus disease 2019 (Covid-19) remains a pandemic with multiple challenges to confirm patient infectivity: lack of sufficient tests, accurate results, validated quality, and timeliness of results. We hypothesize that a rapid 15-minute Point-Of-Care serological test to evaluate past infection complements diagnostic testing for Covid-19 and significantly enhances testing availability.Method: A three arm observational study at Sharp Healthcare, San Diego, California was conducted using the Clungene® lateral flow immunoassay (LFI) and compared with the Cobas® Roche real-time polymerase chain reaction (RT-PCR) results. Arm 1: Thirty-five (35) subjects with confirmed Covid-19 using RT-PCR were tested twice: prior to 14 days following symptom onset and once between 12 and 70 days. Arm 2: Thirty (30) subjects with confirmed Covid-19 using RT-PCR were tested 12-70 days post symptom onset. Arm 3: Thirty (30) subjects with a negative RT-PCR for Covid-19 were tested 1–10 days following the RT-PCR test date.Results: Specificity of confirmed negative Covid-19 by RT-PCR was 100% (95% CI, 88.4%–100.0%); meaning there was 100% negative positive agreement between the RT-PCR and the Clungene® serological test results. Covid-19 subjects tested prior to day 7 of symptom onset were antibody negative. In subjects 7–12 days following symptom onset with a confirmed positive Covid-19 by RT-PCR, the combined sensitivity of IgM and IgG was 58.6% (95% CI, 38.9%–76.5%). In subjects 13–70 days following symptom onset with a confirmed positive Covid-19 by RT-PCR, the combined sensitivity of IgM and IgG was 90.5% (95% CI, 80.4%–96.4%).Conclusion: The Clungene® lateral flow immunoassay (LFI) is a useful tool to confirm individuals with an adaptive immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) indicating past infection. Providing Point-Of-Care results within 15 minutes without any laboratory instrumentation or specialized software has an added value of increasing test availability to patients who have been symptomatic for more than 1 week to confirm past infection. Performance characteristics are optimal after 13 days with a sensitivity and specificity of 90% and 100%, respectively.Statement of novelty: Formal controlled clinical studies of Covid-19 antibody tests have been limited. This study demonstrates the utility of the 15 minute rapid Clungene® test and the potential for expanded use where Covid-19 RT-PCR testing and vaccination is limited.
- OPEN ACCESSBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The application of point of care serological testing can help determine past infection and assist healthcare workers assess patient risk.Method: An observational study of 114 subjects in North Suburban Chicago, Illinois, was performed using the Clungene® lateral flow immunoassay (LFI). Patients’ PCR test results and clinical symptoms were used to compare the seroconversion rate of this patient population with the surrounding community.Results: Excluding 1 aberrant result, there was 100% positive agreement (10) between PCR and antibody (IgG or IgM) test results. There were 7 patients who did not have a prior PCR test who were positive for IgG; 5 of the 7 had clinical symptoms consistent with possible exposure and 2 were asymptomatic. There was 1 person with a suspected exposure to an infected person who was IgM positive. Ninety-five asymptomatic patients were seronegative. The overall rate of 15.9% seroconversion (IgG or IgM) is consistent with other community-based testing results in the North Suburban Chicago, Illinois area.Conclusion: Rapid screening tests to identify antibody positive patients recovered from coronavirus disease-2019 can be a useful tool for healthcare professionals to determine or confirm past infection.Statement of novelty: Limited data is available on the use of point of care serological testing to assist healthcare professionals with the assessment of their patient population regarding past SARS-CoV-2 infectivity and seroconversion. The present study successfully investigated the use of a point of care antibody test in a physician’s office to determine which patients have developed antibodies, indicating an immune response to SARS-CoV-2, and to assist with decisions on whether patients should pursue normal social and workplace activities.
- OPEN ACCESSObjectives: To assess the psychological effects of systemic lupus erythematosus (SLE), including perception of aging, in a cohort of participants who were either diagnosed with SLE or had an affected family member.Methods: Over a period of 1 year, we conducted once-monthly face-to-face interviews with 12 participants. The participants were from 4 related families and include 7 females and 5 males. Three participants had a confirmed diagnosis of SLE. Spouses were also included in this study to assess transitivity of the psychological signs of SLE. Responses to structured interview questions were analyzed to assess the perception of aging.Results: The major complaints in participants diagnosed with SLE were pain and psychological stress. Nephrotic syndrome, urinary tract infection, weight disorders and increased need for psychosocial support were common in the participants’ medical history. Qualitative analysis of questionnaires completed by participants with SLE revealed a correlation of “feeling old” with the non-resolution of health complaints. Family members who did not have SLE also reported “feeling old”. Complaints of stress, anxiety, nervousness and lack of enjoyment of life were common in those who were diagnosed with SLE, as well as those who were not. All spouses reported experiencing digestive disorders, hemorrhoids as well as various phobias, regardless of whether their partners had a confirmed SLE diagnosis.Conclusions: In this study, we found that participants with SLE or those who had a close family member with SLE displayed psychological signs of aging. All participants had a predisposition to anxiety, while spouses developed various phobias.Statement of novelty: We show that individuals with SLE and close family members have an increased self-perception of aging.
- OPEN ACCESS
- Mehdi Yeganeh,
- Tallal Basha,
- Lina Sobhi Abdrabo,
- Sophie Ran Wang,
- Joël Lafond-Lapalme,
- Jean-Baptiste Rivière,
- Duncan Lejtenyi,
- David S. Rosenblatt,
- Christine McCusker,
- Reza Alizadehfar, and
- Bruce D. Mazer
Background: Patients with chromosome 18 abnormalities can present with an immune phenotype that resembles common variable immunodeficiency. Knowledge of the genes underlying the immune defects related to chromosome 18 aberrations could improve our understanding of the molecular basis of primary antibody deficiencies. Here we present a patient with ring chromosome 18 affected by primary antibody deficiency and autoimmunity.Methods: Lymphocyte populations were determined by flow cytometry. Specific antibody response to protein vaccines and pneumococcal capsule antigen were measured by ELISA. Genome sequencing was performed using a PCR-free protocol.Case: The patient was diagnosed with ring chromosome 18 for delayed growth and dysmorphic features at the age of 1 month. Array comparative genomic hybridization showed deletions of 18p11.21-pter and 18q21.31-qter. At the age of 10 months, she started having recurrent episodes of otitis media and pneumonia, as well as autoimmune arthritis. Serum immunoglobulins and specific antibody levels were low. The CD19+CD27+ memory B cell and CD45RO+ T cell populations were decreased. Recurrent infections were controlled with parenteral immunoglobulin and autoimmune arthritis was treated with systemic and intra-articular therapies.Conclusions: Selective IgA deficiency is the most common form of immunodeficiency associated with chromosome 18 abnormalities, however patients with ring chromosome 18 may also be affected by specific antibody deficiency and require immunoglobulin replacement for optimal care. These patients might partially share the same genomic loss as in patients with non-syndromic primary antibody deficiency.Statement of novelty: This report highlights an important teaching point about immune deficiency in a chromosomal anomaly that is not infrequently encountered in pediatric hospitals. Furthermore, our investigations provide more insight into the pathogenesis of immunodeficiency among patients with chromosome 18 abnormalities. - OPEN ACCESSIntroduction: Serum sickness is a type III hypersensitivity reaction. Immune complex deposition activates complement pathways resulting in fever, vasculitic rash, arthritis and lymphadenopathy. Medications are known to trigger serum sickness-like reactions which clinically resemble serum sickness, however, are not thought to involve circulating immune complexes. The full pathophysiology is not clear. Risperidone is an atypical antipsychotic drug commonly used in the paediatric population.Aim: To describe the diagnosis, disease course and outcome of a patient who developed serum sickness-like reaction secondary to risperidone.Methods: Review of patient chart and medical interview in accordance with institutional research ethics board approval.Results: The patient, a 7 year old male with Attention Deficit Hyperactivity Disorder, was started on risperidone 0.25 mg once daily. Within a week the dose was increased to 0.5 mg once daily. During the third week after initiation of medication, the patient developed generalized purpuric, confluent, maculopapular rash. Although the patient did not have any signs and symptoms of a viral illness, he was diagnosed with viral-induced exanthema and continued on risperidone. On day 28, he developed significant, bilateral swelling of upper and lower extremities, facial angioedema, lymphadenopathy, arthralgia and arthritis in ankles, knees, hands and elbows without fever. Investigations showed normal complement C3 and C4 levels. C1 esterase inhibitor, anti-nuclear antibody and urinalysis were normal. Erythrocyte sedimentation rate, C-reactive protein and leukocyte levels were elevated. The diagnosis of serum sickness-like reaction to risperidone was made and the patient subsequently treated with cetirizine, hydrocortisone, and prednisone for 1 week with significant improvement. Skin biopsy was declined by the patients’ parents and therefore was not performed. Provocative oral challenge to risperidone was not considered because of clear suggestive history and ethical consideration.Conclusion: Psychotropic medications are known to cause cutaneous eruptions. Serum sickness-like reactions can happen upon exposure to risperidone. Clinicians should be aware of this potential adverse reaction that can develop weeks after therapy initiation, and be encouraged to discontinue risperidone when the suggestive symptoms emerges.Statement of novelty: We describe a case of serum sickness-like reaction to risperidone in a paediatric patient. To our knowledge, this is the first case of serum sickness-like reaction to risperidone.
