Assessment of Sleep Disorders in Patients with CVID.

Inborn errors of immunity have been associated with reduced health-related quality of life and increased fatigue. Sleep disorders, which have been shown to contribute to fatigue and other health concerns, are prevalent in the general population, but there are limited studies evaluating these conditions in patients with common variable immunodeficiency (CVID). Our aim was to evaluate the prevalence of fatigue, sleep disturbances, and sleep-disordered breathing in adults with CVID. Patients completed 4 validated, self-administered questionnaires and a 1-night disposable home sleep apnea test. Our results demonstrated increased median Patient-Reported Outcomes Measurement Information System fatigue scores of 58.7 in patients with CVID in addition to clinically significant fatigue as measured by Fatigue Severity Scale score (median, 5.2) and overall poor sleep quality based on global Pittsburgh Sleep Quality Index score (median, 9.0). For CVID patients who completed the home sleep apnea test, 76.9% met criteria for sleep-disordered breathing with an Apnea-Hypopnea Index score of 5 or greater. The results of our study indicate that patients with CVID may have increased rates of undiagnosed sleep disorders that may contribute to increased fatigue and reduced health-related quality of life.

Statistical Mechanics Metrics in Pairing and Parsing In Silico and Phenotypic Data of a Novel Genetic NFκB1 (c.T638A) Variant.

(1) Background: Mutations in NFκB1, a transcriptional regulator of immunomodulating proteins, are a known cause of inborn errors of immunity. Our proband is a 22-year-old male with a diagnosis of common variable immunodeficiency (CVID), cytopenias with massive splenomegaly, and nodular regenerative hyperplasia of the liver. Genetic studies identified a novel, single-point mutation variant in NFκB1, c. T638A p. V213E. (2) Methods: Next-generation panel sequencing of the patient uncovered a novel single-point mutation in the NFκB1 gene that was modeled using the I-TASSER homology-modeling software, and molecular dynamics were assessed using the YASARA2 software (version 20.14.24). (3) Results: This variant replaces valine with glutamic acid at position 213 in the NFκB1 sequence. Molecular modeling and molecular dynamic studies showed altered dynamics in and around the rel homology domain, ankyrin regions, and death domain of the protein. We postulate that these changes alter overall protein function. (4) Conclusions: This case suggests the pathogenicity of a novel variant using protein-modeling techniques and molecular dynamic simulations.

Disseminated mycobacterial infections after tumor necrosis factor inhibitor use, revealing inborn errors of immunity.

Tumor necrosis factor-a inhibitors can be associated with increased risk of infections, particularly reactivation of latent tuberculosis or nontuberculous mycobacterium (NTM). However, because disseminated NTM is rare, inborn errors of immunity should be considered. We present three patients with disseminated NTM after tumor necrosis factor-a inhibitor use who were found to have inborn errors of immunity.

Safety and tolerability of Evusheld in patients with CVID: The Mayo Clinic experience.

Background: The past 2 years of the COVID-19 pandemic brought with it many unknowns for patients with immunodeficiency. Because of the concern for severe infection in those with immunocompromise, patients have been eager for effective prevention, vaccination, and treatment strategies. Preexposure prophylaxis provides another means of prevention in those with immunocompromise. A combination of tixagevimab and cilgavimab (Evusheld [AstraZeneca Cambridge, United Kingdom]) was granted emergency use authorization for preexposure prophylaxis at the end of 2021, but questions remained regarding how this would be tolerated and the side effects associated with its use. Objectives: Our aim was to evaluate the safety and tolerability of Evusheld in patients with CVID from our tri-site institution. Methods: We performed an institutional review board-approved, retrospective chart review of patients with common variable immunodeficiency (CVID) who received Evusheld before March 26, 2022. Results: Of the 45 patients with CVID who received Evusheld, 41 (91%) received the recommended full dose of 600 mg. The majority of patients (39 of 45 [87%]) tolerated Evusheld without adverse events. The adverse events reported included immediate injection site pain, fatigue and cough, an episode of shingles, and chest pain. Conclusions: This is an initial report on the safety and tolerability of Evusheld injections in patients with CVID. The majority of patients tolerated the injections without adverse events. For patients with reported chest pain, the results of a subsequent cardiac workup were negative. The efficacy of Evusheld could not be evaluated owing to the short median follow-up of this study (19 days).

Immunoglobulin treatment for B-cell immunodeficiencies.

This article aims to describe the rationale and utility of immunoglobulin therapies in patients with B-cell immunodeficiency states. We describe the historical perspective, mechanism of actions, and indications for use in this population. We then focus upon management pearls and special considerations for its utility. Finally, we elaborate upon the important economic implications for these patients and the need to develop individualized management strategies in this vulnerable population.

Clinical and Phenotypic Characterization of Common Variable Immunodeficiency Diagnosed in Younger and Older Adults.

PURPOSE: Common variable immunodeficiency (CVID) is the most prevalent symptomatic immunodeficiency in adults. Little is known about the manifestations of CVID presenting in older adults. Herein, we performed a phenotypic characterization of patients diagnosed older than age 40. METHODS: A retrospective chart review of 79 patients seen at UF Health between 2006 and 2020 with a verified diagnosis of CVID per the ICON 2016 criteria was conducted. Patients were classified according to four phenotypes: no-disease-related complications, autoimmune cytopenias, polyclonal lymphoproliferation, and unexplained enteropathy. Patients diagnosed with CVID from age 2 to 40 (n = 41, "younger cohort") were compared to patients diagnosed with CVID age 41 and older (n = 38, "older cohort"). RESULTS: Among the younger cohort, pathologic genetic variants, positive family history for immunodeficiency, autoimmunity (49% vs 24%, p = 0.03), and splenomegaly (46% vs 16%, p = 0.004) were more common, as was the "autoimmune cytopenias" phenotype (24% vs 3%, p = 0.007). Among the older cohort, lymphoma (11% vs 0%, p = 0.049) and the "no disease-related complications" phenotype (79% vs 57%, p = 0.03) were more commonly seen. Comorbidities such as bronchiectasis (27% vs 21%, p = 0.61), GI involvement (34% vs 24%, p = 0.33), and GLILD (5% vs 8%, p = 0.67) were equally present among both the younger and older cohorts, respectively. CONCLUSION: The lower incidence of autoimmunity and splenomegaly, as well as overlapping clinical features with immunosenescence, may make diagnosing CVID in older patients more challenging; however, the disease is not more indolent as the risks for lymphoma, bronchiectasis, and GLILD are similar to those of younger patients.

Case Report: Secondary Hemophagocytic Lymphohistiocytosis With Disseminated Infection in Chronic Granulomatous Disease-A Serious Cause of Mortality.

Chronic granulomatous disease (CGD) is a primary immune deficiency due to defects in phagocyte respiratory burst leading to severe and life-threatening infections. Patients with CGD also suffer from disorders of inflammation and immune dysregulation including colitis and granulomatous lung disease, among others. Additionally, patients with CGD may be at increased risk of systemic inflammatory disorders such as hemophagocytic lymphohistiocytosis (HLH). The presentation of HLH often overlaps with symptoms of systemic inflammatory response syndrome (SIRS) or sepsis and therefore can be difficult to identify, especially in patients with a primary immune deficiency in which incidence of infection is increased. Thorough evaluation and empiric treatment for bacterial and fungal infections is necessary as HLH in CGD is almost always secondary to infection. Simultaneous treatment of infection with anti-microbials and inflammation with immunosuppression may be needed to blunt the hyperinflammatory response in secondary HLH. Herein, we present a series of X-linked CGD patients who developed HLH secondary to or with concurrent disseminated CGD-related infection. In two patients, CGD was a known diagnosis prior to development of HLH and in the other two CGD was diagnosed as part of the evaluation for HLH. Concurrent infection and HLH were fatal in three; one case was successfully treated, ultimately receiving hematopoietic stem cell transplantation. The current literature on presentation, diagnosis, and treatment of HLH in CGD is reviewed.

Asplenia and Hyposplenism: An Underrecognized Immune Deficiency.

The number of disorders associated with congenital or acquired asplenia and functional hyposplenism has increased substantially over the past couple decades. Previously, screening for asplenia and hyposplenism was a barrier to identifying patients at risk. Recent methods for measuring splenic function have emerged as accurate and reliable. Identifying patients prevents overwhelming postsplenectomy infection or invasive pneumococcal disease. Approaches to protect patients with asplenia or hyposplenism include patient education of risks and signs/symptoms of infection, vaccination, and antibiotic prophylaxis. Physicians have evaluated methods of preserving splenic function after trauma and sought alternative treatments of refractory cytopenias treated with splenectomy in the past.

Antibiotic Prophylaxis for Dental Treatment in Patients with Immunodeficiency.

Routine antibacterial prophylaxis is recommended before dental procedures in select patient populations. Currently, no guidelines are in place for routine prophylaxis before dental procedures in patients with primary immunodeficiency diseases. We review risk factors and provide recommendations on routine dental care and antibacterial prophylaxis in patients with primary immunodeficiency diseases.