Overview of subcutaneous immunoglobulin 16.5% in primary and secondary immunodeficiency diseases

Most primary immunodeficiency diseases, and select secondary immunodeficiency diseases, are treated with immunoglobulin (IG) therapy, administered intravenously or subcutaneously (SCIG). The first instance of IG replacement for primary immunodeficiency disease was a 16.5% formulation administered subcutaneously in 1952. While most SCIG products are now a 10 or 20% concentration, this review will focus on SCIG 16.5% products with a historical overview of development, including the early pioneers who initiated and refined IG replacement therapy, as well as key characteristics, manufacturing and clinical studies. In determining an appropriate IG regimen, one must consider specific patient needs, characteristics and preferences. There are advantages to SCIG, such as stable serum immunoglobulin G levels, high tolerability and the flexibility of self-administered home treatment.

Atopic manifestations are underestimated clinical features in various primary immunodeficiency disease phenotypes

Background: Atopic manifestations are describedas clinical feature of variousprimary immunodeficiency disease (PID) phenotypes and in particular frequently reported in the combined immune deficiencies. The prevalence of atopic manifestations in other PIDs remains largely unknown. Objective: To evaluate the prevalence of atopic manifestations in other PIDs and to identify in which PIDsatopic manifestations are most common in order to improve patient care. Methods: A partner-controlled questionnaire-based study was performed in pediatric and adult PID patients. Subsequently, data of diagnostic tests for atopic manifestations (i.e. diagnostic criteria for AD, spirometry, specific IgE against food and inhalant allergens) were collected in adult patients to confirm patient-reported atopic manifestations. Results: Forty-seven children and 206 adults with PIDs, and 56 partner-controls completed the questionnaire. Thirty-five (74.5%) pediatric and 164 (79.6%) adult patients reported to have ever experienced one or more atopic manifestations compared with 28 (50.0%) partner-controls. In adult patients vs. partner-controls, prevalence of atopic dermatitis was 49.5% vs. 27.3% (p=0.003), food allergy10.7% vs. 1.9% (p=0.031), asthma 55.7% vs. 14.8% (p<0.001) and allergic rhinitis 49.8% vs. 21.8% (p<0.001).The frequency of current atopic manifestationsreported by patients washigher than the prevalence based on diagnostic tests (atopic dermatitis 11.2%, food allergy 1.9%, asthma 16.4% and allergic rhinitis 11.5%). Conclusions: Atopic manifestations are prevalent clinicalfeatures in a large spectrum of PIDs and in our cohort frequently present in patients with combined immune deficiencies and predominant antibody deficiencies. Evaluation of atopic manifestations should be considered in patients with PIDs.

Epidemiological Features and Predictors of Mortality in Patients with COVID-19 with and without Underlying Hypertension

Backgrounds. Individuals with hypertension are at higher risk of COVID-19 infection and related mortality. This study was carried out to assess the epidemiological features and predictors of mortality in patients with COVID-19 with hypertension. Methods. In this retrospective study, the epidemiological characteristics of two groups of patients with COVID-19 with hypertension (1927) and without hypertension (39030) were compared. Chi-square test was applied to evaluate the differences between qualitative variables in two study groups. Logistic regression was also used to determine predictors of mortality in patients with COVID-19 and in patients with COVID-19 with hypertension. Results. The prevalence of hypertension in patients with COVID-19 was 4.7%, and 24.37% of COVID-19 related deaths occurred in these individuals. The average age of hypertension and nonhypertension patients was 61 and 37 years, respectively. Fever, cough, headache, anorexia, fatigue, and comorbid diseases, such as cardiovascular disease, chronic lung and kidney disease, diabetes, immunodeficiency disease, and thyroid disease, were significantly more frequent in people with hypertension than those without hypertension. The chances of mortality in patient with COVID-19 were 1.8 times higher in individuals with dyspnea, 1.25 in individuals with fever, 1.33 in individuals with cough, 3.6 in patients with hypertension, 2.21 in diabetics, and 2.2 in individuals with cardiovascular disease. Also, individuals with COVID-19 with hypertension that had dyspnea, immunodeficiency, and cardiovascular disease were at higher risk of mortality. Conclusion. Hypertension is a serious threat to patients with COVID-19. Therefore, in order to control these patients more precisely and reduce mortality in them, it is extremely important to develop prevention and treatment strategies.

The Evaluation of Neutropenia in X-linked Agammaglobulinemia Patients

Objectives: X-linked Agammaglobulinemia (XLA) is a primary immunodeficiency disease, characterized by severe hypogammaglobulinemia and the low numbers of peripheral B cells. Neutropenia is a rare complication among the XLA patients, which may lead to a higher rate of infections and morbidity. The aim of the authors is to assess the correctness of this issue. Methods: In this study, we compared demographic, clinical and laboratorial data between two groups of XLA patients, with and without neutropenia. Results: Frequency of neutropenia was 15% in our population. Infectious complications were the most prevalent clinical manifestations, regardless of the presence of neutropenia. However, Lymphoproliferative complication was significantly higher in the neutropenic patients (p = 0.001). No significant difference in mortality rate was observed between the groups. Conclusion: Neutropenia is a rare complication among the XLA patients, and significantly decreases the mean age of XLA diagnosis in the patients. But it is not related to the higher frequency of infectious diseases in the neutropenic patients compared to non-neutropenic ones.

Loss of function mutation in ELF4 causes autoinflammatory and immunodeficiency disease in human

Monogenic autoinflammatory diseases (mAIDs) are a heterogeneous group of diseases affecting primarily innate immunity, with various specific genetic causes. Genetic diagnosis of mAIDs can assist in the patient's management and therapy. However, a large number of sporadic and familial cases remain genetically uncharacterized. Here, we described a pediatric patient suffering from recurrent viral and bacterial respiratory infection, refractory oral ulcer and constipation, who was clinically diagnosed of inborn errors of immunity (IEI). In an effort to establish genetic diagnosis, no known causative genes were identified by whole-exome sequencing. However, manually going through bioinformatically predicted candidate genes, we suspected and prioritized ELF4 (chrX:129205133 A>G, c.691T>C, p.W231R) as the genetic cause for our patient. We then evaluated the pathogenicity of this mutation by both various bioinformatic methods and preliminary but definitive experimental approach. Our data suggested that W231R mutant ELF4 is a "loss of function" mutation causing decreased protein stability and decreased trans-activation activity. Thus, we identified a novel mAID, which we termed "X-linked autoinflammatory and immunodeficiency disease associated with ELF4, X-AIDE".

Characterization of a Cohort of Patients With LIG4 Deficiency Reveals the Founder Effect of p.R278L, Unique to the Chinese Population

DNA ligase IV (LIG4) deficiency is an extremely rare autosomal recessive primary immunodeficiency disease caused by mutations in LIG4. Patients suffer from a broad spectrum of clinical problems, including microcephaly, growth retardation, developmental delay, dysmorphic facial features, combined immunodeficiency, and a predisposition to autoimmune diseases and malignancy. In this study, the clinical, molecular, and immunological characteristics of 15 Chinese patients with LIG4 deficiency are summarized in detail. p.R278L (c.833G&gt;T) is a unique mutation site present in the majority of Chinese cases. We conducted pedigree and haplotype analyses to examine the founder effect of this mutation site in China. This suggests that implementation of protocols for genetic diagnosis and for genetic counseling of affected pedigrees is essential. Also, the search might help determine the migration pathways of populations with Asian ancestry.

Persistent COVID-19 lung infection in a child with a primary immunodeficiency

SARS-CoV-2 infection in children with primary immunodeficiency disease (PID) and its complications have not yet been well described, the course of COVID-19 can range from mild illness to death. We aim to report the case of a child with a PID who develop a severe and persistent pulmonary COVID-19 infection. We present chronologically his clinical course, tests, interventions and radiological findings showing his irregular evolution and poor response to infection. This case highlights the need to accurately monitor the immune response in these cases to try to stop the progression of the damage.

The Epidemiology and Clinical Presentations of Atopic Diseases in Selective IgA Deficiency

Selective IgA deficiency (sIgAD) is the most common primary immunodeficiency disease (PID), with an estimated occurrence from about 1:3000 to even 1:150, depending on population. sIgAD is diagnosed in adults and children after the 4th year of age, with immunoglobulin A level below 0.07 g/L and normal levels of IgM and IgG. Usually, the disease remains undiagnosed throughout the patient’s life, due to its frequent asymptomatic course. If symptomatic, sIgAD is connected to more frequent viral and bacterial infections of upper respiratory, urinary, and gastrointestinal tracts, as well as autoimmune and allergic diseases. Interestingly, it may also be associated with other PIDs, such as IgG subclasses deficiency or specific antibodies deficiency. Rarely sIgAD can evolve to common variable immunodeficiency disease (CVID). It should also be remembered that IgA deficiency may occur in the course of other conditions or result from their treatment. It is hypothesized that allergic diseases (e.g., eczema, rhinitis, asthma) are more common in patients diagnosed with this particular PID. Selective IgA deficiency, although usually mildly symptomatic, can be difficult for clinicians. The aim of the study is to summarize the connection between selective IgA deficiency and atopic diseases.

Clinical Application of Metagenomic Next-Generation Sequencing for Suspected Infections in Patients With Primary Immunodeficiency Disease

BackgroundInfections are the major cause of morbidity and mortality in patients with primary immunodeficiency disease (PID). Timely and accurate microbiological diagnosis is particularly important in these patients. Metagenomic next-generation sequencing (mNGS) has been used for pathogen detection recently. However, few reports describe the use of mNGS for pathogen identification in patients with PID.ObjectiveTo evaluate the utility of mNGS for detecting pathogens in patients with PID, and to compare it with conventional microbiological tests (CMT).MethodsThis single center retrospective study investigated the diagnostic performance of mNGS for pathogens detection in PID patients and compared it with CMT. Sixteen PID patients with suspected infection were enrolled, and medical records were analyzed to extract detailed clinical characteristics such as gene variation, immune status, microbial distribution, time-consuming of mNGS and CMT, treatment, and outcomes.ResultsmNGS identified pathogenic microbe in 93.75% samples, compared to 31.25% for culture and 68.75% for conventional methods, and detected an extra 18 pathogenic microorganisms including rare opportunistic pathogens and Mycobacterium tuberculosis. Pathogen identification by mNGS required 48 hours, compared with bacterial culture for 3-7 days and even longer for fungus and Mycobacterium tuberculosis culture.ConclusionsmNGS has marked advantages over conventional methods for pathogenic diagnosis, particularly opportunistic pathogens and mixed infections, in patients with PID. This method might enable clinicians to make more timely and targeted therapeutic decisions, thereby improving the prognosis of these patients.