September Update for Inborn Errors of Immunity

38 PUBMED indexed articles were published in the month of September 2020.

COVID-19 and PID

Zang et al report defects in TLR3- and IRF7-dependent type I IFN immunity that may predispose patients to life-threatening COVID-19 pneumonia
Bastard et al report auto-antibodies against IFN-ω and IFN-α that neutralize the action of type I IFNs against Sars-Cov2
Meyts et al report the clinical presentation and outcomes of 94 patients with Inborn errors of immunity

Genetics/ Reviews/ Updates

Platt et al compared the efficacy and economics of targeted gene panels and Whole-exome sequencing for patients with PID. They concluded that the diagnostic yield of the targeted panel was 56% and of subsequent WES was 58%. Use of only WES had a yield of only 45%. The cost analysis showed that the WES only approach demonstrated savings of 300-950 USD depending on the diagnostic yield. The advantages of WES being simplified workflow, reduced costs and potential to identify novel diseases.
Chinn et al reviewed the use of genetic testing in PID patients. Massively parallel high-throughput sequencing is the most useful. The yield for WES and WGS is better in consanguineous families. Targeted panels are cost-effective panels which can be used initially.
Leonardi et al reviewed the expanding spectra of PID disorders and they suggest screening for immunodeficiency in patients with lymphoproliferation or early-onset/multiple autoimmune diseases
Delplanque et al reviewed AA amyloidosis (AAA) in PID patients and report French cases with AAA.Renal involvement was the commonest and bronchiectasis is an important risk factor

Infections in PID

- Lafont et al reviewed Nocardiosis in PID retrospectively from French and US database. It was most commonly associated with CGD followed by IL-12p40 deficiency.
- Bargir et al highlight the important clues in patients reported with chalazion pointing towards the diagnosis of PID
- Ochoa et al review genetic susceptibility of fungal infections in children. Recurrent or severe fungal infections is an important clue to look for underlying PID

Combined Immunodeficiency disorders with associated or syndromic features

Wiskott Aldrich Syndrome

Barutcu et al report a 7 yr old boy with Wiskott Aldrich syndrome who had an ascending aortic aneurysm. They recommend periodic echo and MRI to evaluate for underlying aneurysms

Hyper IgE Syndromes

Meixner et al report the importance of early intervention for retained primary dentition in Hyper IgE syndrome. They recommend extraction of retained primary incisors before 9 years and retained molars and canines before 13 years of age after the radiograph shows the presence of the permanent successor teeth

Predominantly antibody deficiencies

X linked Agammaglobulinemia

Daou et al report a rare case of a 47 yr old XLA patient with T-large granular lymphocyte leukaemia (T-LGLL) also associated with CD8+ cutaneous lymphoproliferation
Hu et al reported a case of 5 yr old boy with a novel deletion in BTK gene
Gracia-Morato et al report an atypical XLA patient with a mutation in the promotor region. He had low B cells, hypogammaglobulinemia, and oscillating neutropenia

Common Variable Immunodeficiency Disorders

Weifenbach et al reported the global distribution of CVID in the context of the Human Development Index. They analyzed 74 datasets from 47 countries. The prevalence ranged from 0.001 to 3.374 per 100,000 with higher prevalence being in countries with high HDI. This might be because of documentation in registries. Poor awareness in low and middle HDI countries might be the reason for this discrepancy.
Maréchal et al report a long term survival of an NFKB1 deficient patient with progressive multifocal leukoencephalopathy. The patient was managed with mirtazapine and mefloquine, it showed improvement on MRI and CSF analysis though the patient was severely disabled.
Molina et al report an assay for the intracellular expression of Akt and S6 by flow cytometry and their phosphorylation status in both baseline conditions and upon B-cell receptor activation with anti-IgM in various primary B-cell subsets of patients with CVID and APDS
Molina et al also report reduced Bcl-2 protein levels in memory B cells from CVID patients
Mandola et al report a combined immunodeficiency phenotype due to a novel homozygous NFKB1 mutation resulting in a defective T and B cell function

Diseases of Immune dysregulation

- Chan et al reviewed the expanding spectrum of diseases of immune dysregulation and introduce the concept of ‘Primary immune regulatory disorder’ or ‘PIRD’

CTLA4 deficiency

Zaremehrjardi et al report a case of 24-year-old CTLA4 haploinsufficient male who presented with multiple autoimmune manifestations

X linked lymphoproliferative disease type 1

Chartier et al report a 5 year old boy who had undergone liver transplantation followed by an EBV-driven post-transplant lymphoproliferative disease which turned out to be XLP1 deficiency which eventually needed HSCT

Congenital defects of phagocyte number, function, or both

Sprenkeler et al report loss of function mutation in CSF3R with moderate neutropenia with mature neutrophils supporting the notion that the major role of G‐CSF in neutrophil expansion and release may be during inflammation when increased bone marrow output is required

Defects in Intrinsic and Innate immunity

Partanen et al report 2 patients with hantaa viruses encephalitis having heterozygous TLR3 mutation
Sakata et al report an autosomal recessive STAT1 deficient patient with increased susceptibility to mycobacteria and viruses due to compound heterozygous intronic variants

Auto-inflammatory DIsorders

Broderick et al give an Allergist and Immunologists perspective on recurrent fevers and auto-inflammation in children. They suggest important historical features and initial lab investigations to be used in the management of these cases

Hematopoietic Stem Cell Transplantation

Olaya et al report a multi-centre transplantation experience from Colombia
Chiesa et al did a retrospective study of 635 children and 77 adults with underlying CGD who underwent HSCT. Older age was associated with increased GVHD and reduced survival. They report very good outcomes in CGD after allo-HSCT. In a presence of a matched donor, it is recommended that they undergo HSCT at a younger age
Holzer et al compared the outcome fo matched vs haploidentical HSCT in children with PID. They conclude that in the absence of a suitable HLA-identical family donor haploidentical HSCT may be a viable option

Other Management in PID

Moschese et al compared effectiveness of weekly and biweekly Subcutaneous Immunoglobulin in pediatric PID patients. Both groups maintained comparable trough Ig levels and were equally effective
Kher Ng et al reviewed impulse oscillometry, new bronchoscopic techniques for sampling, the concept of the human airway microbiome, and new treatment approaches for bronchiectasis and interstitial lung disease in patients with PID
Rai et al reviewed the latest advancements in gene therapy for PID patients

Newborn Screening

Thomas et al reviewed the need for newborn screening for SCID from the French perspective and conclude with its feasibility and effectiveness

Questionnaire

Jones et al described a patient-centric questionnaire to detect the burden of Immunoglobulin therapy (IgBot-35). It may help in customizing Ig therapy for PID patients
West et al reported the experiences of family caregivers of children with Primary Immunodeficiency in view of care demands and highlight the role of the social support networks
Toms et al report a modified immunodeficiency disease-related (IDR) score that can aid in PID diagnosis in adult patients