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.

A Review of Primary Immunodeficiency Diseases with Skin Manifestations

Introduction: Primary immunodeficiencies (PID) are rare heterogeneous disorders with defects in which one or more components of the immune system are malfunctioning. Clinical presentations of the patients according to type of immunodeficiency are variable. The majority of these patients are susceptible to infections depending on the type of disorder. In these patients, one of the most important and common symptoms is a skin manifestation that in many cases helps to diagnose the disease. Skin symptoms can include infectious-inflammatory-autoimmune-allergic manifestations and malignancies. In some cases, skin involvement can be the initial manifestation of immunodeficiency diseases, so understanding the relationship between the type of primary immunodeficiency and the type of skin involvement is very important in diagnosing the disease. The majorities of skin diseases are not pathogenomonic in primary immunodeficiencies and may be seen in other diseases with normal levels of immunity. However, there are numerous skin findings that are so characteristic of immunodeficiency diseases that it is necessary to evaluate the immune system. Conclusion: Skin is an organ that may be involved in many diseases, including primary immunodeficiency. Sometimes skin is the first organ involved in immune deficiencies. Therefore, recognizing skin manifestations in these patients is one of the most important factors in early diagnosis of these people.

Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases

Aim: This post hoc analysis evaluated the efficacy and overall tolerability of immunoglobulin (Ig) treatment modalities (intravenous Ig [iv.Ig], subcutaneous Ig [sc.Ig] and facilitated sc.Ig [fsc.Ig]). Materials & methods: A total of 30 participants with primary immunodeficiency diseases aged ≥2 years sequentially received iv.Ig, sc.Ig and fsc.Ig during consecutive clinical studies. Results: For iv.Ig, sc.Ig and fsc.Ig, rates of validated acute serious bacterial infections/participant-year (0, 0.09 and 0.04, respectively) and all infections/participant year (4.17, 3.68 and 2.42, respectively) were similarly low; rates of systemic and local causally related adverse events/participant-year were 5.60, 1.93 and 0.88, respectively and 0.13, 0.92 and 1.57, respectively. Conclusion: fsc.Ig provided similar efficacy to iv.Ig and sc.Ig. Clinical Trial registration: NCT00546871 , NCT00814320 , NCT01175213 (ClinicalTrials.gov)

Reversion Mosaicism in Primary Immunodeficiency Diseases

Reversion mosaicism has been reported in an increasing number of genetic disorders including primary immunodeficiency diseases. Several mechanisms can mediate somatic reversion of inherited mutations. Back mutations restore wild-type sequences, whereas second-site mutations result in compensatory changes. In addition, intragenic recombination, chromosomal deletions, and copy-neutral loss of heterozygosity have been demonstrated in mosaic individuals. Revertant cells that have regained wild-type function may be associated with milder disease phenotypes in some immunodeficient patients with reversion mosaicism. Revertant cells can also be responsible for immune dysregulation. Studies identifying a large variety of genetic changes in the same individual further support a frequent occurrence of reversion mosaicism in primary immunodeficiency diseases. This phenomenon also provides unique opportunities to evaluate the biological effects of restored gene expression in different cell lineages. In this paper, we review the recent findings of reversion mosaicism in primary immunodeficiency diseases and discuss its clinical implications.

Facilitated subcutaneous immunoglobulin use in pediatric patients with primary or secondary immunodeficiency diseases

Aim: While facilitated subcutaneous immunoglobulin (fSCIG) has been evaluated in pediatric patients with primary immunodeficiency diseases in clinical trials, real-world data are lacking. Materials & methods: This multicenter, retrospective, chart review study assessed fSCIG utilization in 30 patients less than 18 years old, with primary or secondary immunodeficiency diseases. Medical records were reviewed at fSCIG initiation and at 6 months. Results: Most (90%) patients received their first fSCIG infusion at a medical facility; by 6 months, all fSCIG infusions were administered at home by the patient/caregiver, the majority infusing every 3–4 weeks into a single site. No serious adverse drug reactions occurred. Conclusion: This study supports the feasibility and tolerability of administering fSCIG at home to pediatric patients with immunodeficiencies. Clinical Trial Registration: DRKS00015436 ( German Clinical Trials Register )

Professor Asghar Aghamohammadi (1951-2020)

Professor Asghar Aghamohammadi, the founder of the Immunology and Genetics Journal, passed away on November 14th, 2020, at the age of 69. We were terribly shocked by his death due to the Coronavirus Disease 2019 (COVID-19), while he had been working continuously and actively until late October, before his admission to the hospital because of an infection by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Professor Aghamohammadi was born in 1951 in Khouzestan Province, Iran. After completing his primary education in Ahvaz, he studied medicine in Mashad University of Medical Sciences and Jundishapur University of Medical Sciences. After graduating in 1978, he joined the Red Crescent Organization in Iran. Afterwards, he continued his education in pediatrics in 1984, followed by a fellowship in clinical immunology and allergy in 1988. Consequently, he became the faculty member in the Department of Pediatrics, Children’s Medical Center, Tehran University of Medical Sciences, where he dedicated all his life researching on the Primary Immunodeficiency Diseases (PIDs), by making the infrastructure for increasing the general awareness about PIDs, conducting fundamental research on PIDs, and facilitating the diagnosis and treatment of patients with PIDs. Professor Aghamohammadi established the “Iranian Association for PID Patients Support”, the “Iranian Primary Immunodeficiency Diseases Registry (IPIDR)”, “Research Center for Immunodeficiencies”, “Iranian PID Network”, and the “Immunology and Genetics Journal”. His international collaborations and hard works, along with his honesty, are some of his landmarks, which made him one of the world’s scientists top 1%. This is what the young generation should learn from him. The international PIDs communities, including the European Society for Immunodeficiencies (ESID), the Clinical Immunology Society (CIS), the International Patient Organization for Primary Immunodeficiencies (IPOPI), the Jeffrey Modell Foundation (JMF), and the J Project respect him a lot and cannot forget his amazing efforts in the field of PIDs for all these years. We all at the Research Center for Immunodeficiencies (RCID) and the Immunology and Genetics Journal (IGJ), are still in shock and cannot imagine continuing without him. We will not forget that the father of the PIDs in Iran was a remarkable scientist. He will remain in the minds and hearts of all those who were close to him. May his name be always remembered with respect and love.