Figure 5.
Proportions of cases explained. The highest proportions of cases explained for infections striking otherwise healthy patients (i.e., excluding conventional primary immunodeficiencies; see the table and text for references). (1) For rare Mendelian infections, which are often familial, MSMD is explained in 50–60% of cases by mutations of 22 genes and 46 allelic forms. Its prevalence is about 1/20,000 individuals. (2) For rare infections due to rare cytokine-neutralizing auto-Abs, infections with weakly virulent mycobacteria that phenocopy MSMD are explained by type II IFN auto-Abs in ∼5% of adult cases. (3) For common monogenic infections, which are typically sporadic, tuberculosis (TB) is explained in at most 1% of cases, and only in populations of European descent, by homozygosity for common variants of TYK2 or IL23R. The contribution of rare monogenic infections also underlying MSMD (e.g., IL-12Rβ1 deficiency), or specific to TB (e.g., TNF and LY9 deficiencies), is numerically much more modest. (4) For rare non-Mendelian monogenic infections, which are typically sporadic, HSE is explained in 10% of children by mutations of 19 genes. Its prevalence is about 1/20,000 individuals. (5) Finally, for common infections due to common cytokine-neutralizing auto-Abs, sporadic WNV encephalitis is explained in 40% of cases by auto-Abs neutralizing type I IFNs. Its prevalence is about 1/200 infected individuals. Refer to the image caption for details. The figure consists of five pie charts, each representing a different condition. The first chart, labeled M S M D Genetic, covers fifty to sixty percent of cases. The second chart, labeled M S M D Type 2 I F N auto-Abs, accounts for five percent of cases. The third chart, labeled Tuberculosis Genetic, represents one percent of cases. The fourth chart, labeled Herpes simplex encephalitis Genetic, covers ten percent of cases. The fifth chart, labeled W N V encephalitis Type 1 I F N s auto-Abs, accounts for forty percent of cases. Each chart shows a red portion indicating the proportion of explained cases. The figure provides a visual representation of the varying proportions of cases explained by different genetic and autoimmune factors.

Proportions of cases explained. The highest proportions of cases explained for infections striking otherwise healthy patients (i.e., excluding conventional primary immunodeficiencies; see the table and text for references). (1) For rare Mendelian infections, which are often familial, MSMD is explained in 50–60% of cases by mutations of 22 genes and 46 allelic forms. Its prevalence is about 1/20,000 individuals. (2) For rare infections due to rare cytokine-neutralizing auto-Abs, infections with weakly virulent mycobacteria that phenocopy MSMD are explained by type II IFN auto-Abs in ∼5% of adult cases. (3) For common monogenic infections, which are typically sporadic, tuberculosis (TB) is explained in at most 1% of cases, and only in populations of European descent, by homozygosity for common variants of TYK2 or IL23R. The contribution of rare monogenic infections also underlying MSMD (e.g., IL-12Rβ1 deficiency), or specific to TB (e.g., TNF and LY9 deficiencies), is numerically much more modest. (4) For rare non-Mendelian monogenic infections, which are typically sporadic, HSE is explained in 10% of children by mutations of 19 genes. Its prevalence is about 1/20,000 individuals. (5) Finally, for common infections due to common cytokine-neutralizing auto-Abs, sporadic WNV encephalitis is explained in 40% of cases by auto-Abs neutralizing type I IFNs. Its prevalence is about 1/200 infected individuals.

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