Our recent paper
Germline TET2 loss of function causes childhood immunodeficiency and lymphoma(Stremenova Spegarova et al., 2020) has been
credited for a newly added immune gene in Novel inborn errors of immunity: an Interim Update by the IUIS Committeefull link,
pdf,
as TET2 in table 1(Tangye et al., 2021).
It has been included for the gene list of Autoinflammatory diseases based on our work in 3 patients, 2 families with autosomal recessive loss-of-function.
Since I began research on the genomics of immunology, the IUIS list of genes has been an extremely important reference for my work to which I am now thrilled to give back.
International Union of Immunological Societies (IUIS) IUIS.org;
The International Union of Immunological Societies (IUIS) is an umbrella organization for many of the regional and national societies of immunology throughout the world. As articulated in its Constitution, the objectives of IUIS are:
to organize international co-operation in immunology and to promote communication between the various branches of immunology and allied subjects
to encourage within each scientifically independent territory co-operation between the Societies that represent the interests of immunology
to contribute to the advancement of immunology in all its aspects.
From Novel inborn errors of immunity: an Interim Update by the IUIS Committee,
Inborn errors of immunity (IEI) are generally considered to result from monogenic germline defects that manifest as increased susceptibility to severe and/or recurrent infectious diseases, autoimmune or autoinflammatory conditions, atopic manifestations, and hematopoietic or solid tissue malignancies [1].
Over the past decade, the discovery of new IEIs has been occurring at an impressive rate.
Indeed, the 2011 biennial update published by the IUIS Committee update listed 191 IEIs; this number increased to 430 in the 2019 update
[2],
[3].
This near-exponential increase in gene discovery is being driven by the accessibility and affordability of next-generation sequencing, and the efficient application of these technologies to elucidate the molecular etiology of unsolved cases of IEIs that are likely to result from single-gene defects
4.
Over the last 12 months, we have witnessed the ongoing rapid identification, and occasionally detailed molecular, biochemical, and cellular characterization, of genetic variants that cause, or are at least associated with, human diseases impacting host defense or immune regulation.
Here, we will summarize reports on variants detected in 26 genes which we consider represent novel IEI
(Table 1).
Many additional genetic variants have been reported recently.
However, those listed here have been adjudicated by the IUIS Committee to meet the strict criteria to be considered disease-causing
57.
Our paper took several years to complete,
although the genomic analysis worked incredibly well in this case -
a patient presented as described in figure 1 (Fig. S3 in publication);
after running the routine pipeline that we had made, the result was immediately the top candidate, number one, as cause of disease in a single patient, lymphoma with immunodeficiency and autoinflammtory disease
(Stremenova Spegarova et al., 2020).
We then found that our collaborator had a second family with a LoF in the same gene causing the same severe immunological features.
By combining the families for further genomic and functional analysis work over several years we finally produced a robust explanation for the disease and strong evidence of the immunological features.
The summarised information can be read in
Table 1 Newly validated inborn errors of immunity.
Figure 1. Patient histories as shown in the published
Supplemental Figure S3: Clinical timelines
(this version with legend is an extract my PhD thesis).
(pdf version).
