European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline : Deficiencies, Diagnosis, and Management

This guideline aims to describe the complement system and the functions of the constituent pathways, with particular focus on primary immunodeficiencies (PIDs) and their diagnosis and management. The complement system is a crucial part of the innate immune system, with multiple membrane-bound and soluble components. There are three distinct enzymatic cascade pathways within the complement system, the classical, alternative and lectin pathways, which converge with the cleavage of central C3. Complement deficiencies account for similar to 5% of PIDs. The clinical consequences of inherited defects in the complement system are protean and include increased susceptibility to infection, autoimmune diseases (e.g., systemic lupus erythematosus), age-related macular degeneration, renal disorders (e.g., atypical hemolytic uremic syndrome) and angioedema. Modern complement analysis allows an in-depth insight into the functional and molecular basis of nearly all complement deficiencies. However, therapeutic options remain relatively limited for the majority of complement deficiencies with the exception of hereditary angioedema and inhibition of an overactivated complement system in regulation defects. Current management strategies for complement disorders associated with infection include education, family testing, vaccinations, antibiotics and emergency planning.Peer reviewe

Tolerability of subcutaneous immunoglobulin 20%, Ig20Gly, in pediatric patients with primary immunodeficiencies

Aim: To assess Ig20Gly tolerability in pediatric patients with primary immunodeficiencies. Patients & methods: Infusion parameters and tolerability were analyzed in pediatric patients (aged 2-5 years [n=6], 6-11 years [n=22] and 12-17 years [n=22]) receiving Ig20Gly in two Phase II/III trials. Results: Of 2624 Ig20Gly infusions, >99% did not require any rate reduction, interruption or discontinuation due to adverse events (AEs). Median maximum infusion rates and volumes/site were higher in patients 12-17 years of age (30ml/h/site; 30ml/site) versus 6-11 years (20ml/h/site; 15ml/site) and 2-5 years (18ml/h/site; 14ml/site). Rates of causally related systemic and local AEs (0.009 and 0.063 AEs/infusion) were low. Conclusion: Ig20Gly infused at relatively high rates and volumes was well tolerated in children

The international WAO/EAACI guideline for the management of hereditary angioedema—The 2021 revision and update

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients

The international WAO/EAACI guideline for the management of hereditary angioedema - The 2021 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2), by providing guidance on common and important clinical issues, such as: 1) How should HAE be diagnosed? 2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? 3) What are the goals of treatment? 4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast feeding women? 5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients

Primary immunodeficiency in southern Sweden. Strategies for diagnosis and clinical management

The overall aim of this PhD project was to gain insight into the incidence of primary immunodeficiency (PID) in southern Sweden and to optimize diagnostic and treatment measures for these patients. We estimated the occurrence rate of PID in the pediatric population of southern Sweden during a period of 4 years and described the demographic, clinical and immunological characteristics of the identified cases. The occurrence rate of PID was about four new cases per year in this population. Several different PID diagnoses were found, and the application of specified criteria to identify PID patients was useful. In children who are prone to infection, the use of a predefined set of immunological laboratory analyses at their first examination was beneficial for early identification of patients with primary immunodeficiency. Complement C2 deficiency (C2D) is associated with immunological diseases and increased susceptibility to invasive infections caused by encapsulated bacteria such as Neisseria (N.) meningitidis. We evaluated the immunogenicity of vaccination against N. meningitidis in C2D patients and healthy controls who received a tetravalent meningococcal vaccine. Response was measured by determining serum bactericidal antibody (SBA) titers against the four meningococcal serogroups A, C, Y and W included in the vaccine. We also investigated other immunological factors that could influence the vaccine responses. In general, vaccination against meningococci gave rise to antibody responses in the C2D patients that equal those of healthy controls. The response rate was lower to serogroup A and among C2D patients with history of invasive infections. The presence of G2M*n/G2M*n genotype was associated with higher SBA titers after immunization. None of the other tested immunological factors influenced the vaccination responses. We described the first Swedish patient with purine nucleoside phosphorylase (PNP) deficiency with novel mutations in the PNP gene. We presented also the results of the hematopoietic stem cell transplantation (HSCT) and evaluated the impact of HSCT on the neurological symptoms. We could conclude that HSCT is curative for the immunological defect caused by PNP deficiency and our case strengthens earlier reports that HSCT is effective as a treatment even for neurological symptoms in PNP deficiency. We presented a novel approach of treating SCID by successfully combining a haploidentical HSCT with a subsequent donor lymphocyte infusion (DLI). No acute or chronic graft-versus-host disease (GvHD) was observed after any of the procedures. The HSCT graft was selectively depleted of potentially GvHD-inducing α/β T-cells while the DLI graft was enriched for memory T-cells for enhanced anti-viral immunity. HSCT engraftment was rapid with complete donor chimerism and after DLI the T-cell levels normalized and all infections were cleared

Add-on or alone? Inhaled nebulized immunoglobulin reduces upper airway infections : 24 months of real-life experience

Background: Patients with antibody deficiencies might suffer from acute/chronic upper respiratory tract infections (URTI), despite apparently adequate levels of replacement IgG. This pilot study aimed to ascertain whether inhaled nebulized immunoglobulin (INHIG) could reduce the number of URTI episodes. Methods: Three young, male sibling patients with antibody deficiency who, despite ongoing treatment, were suffering from frequent URTI and recurrent otitis media. INHIG consisted of 4 ml intravenous immunoglobulin (IVIG; 5%) nebulized with the eFLOW® nebulizer, twice daily. Data from meticulous infection symptoms diaries were used for analysis. Results: The patients tolerated the INHIG well; no adverse events were registered. The number of URTI was significantly decreased. Conclusion: In antibody deficient patients with URTI, INHIG reduces the incidence of URTI and may serve as a valuable physiological prophylaxis in the prevention of infections

Immunologic findings in young children with early onset of acute otitis media.

Abstract Conclusion: No significant differences in the number of immune aberrations were seen between children with or without severe recurrent acute otitis media (rAOM); however, subnormal values of immunological markers were found more often than expected, and 4 of the 60 children had treatment-requiring immune deficiencies