Antibody Deficiency Panel

About Predominantly Antibody Deficiencies

Predominantly antibody deficiencies (PADs) represent the most common primary immunodeficiencies, accounting for approximately 50-60% of cases^1-4. These disorders are characterized by impaired antibody production and/or reduced serum immunoglobulin levels and function⁵. The four main categories of PADs include common variable immunodeficiency (CVID), hyper IgM syndromes, agammaglobulinemia, and other isotype or functional deficiencies^5-6. CVID is the most frequent PAD, affecting approximately 1 in 25,000 births, and presenting with hypogammaglobulinemia due to impaired B cell differentiation and subsequently failed antibody production⁷. Hyper-IgM syndrome features increased IgM and decreased IgG, IgA, and IgE levels due to class switch recombination defects, while agammaglobulinemia results from B-cell maturation defects^8-9. Early identification of PAD helps to reduce serious infections and irreversible organ damage, through targeted treatment options. The genetic landscape of PADs is heterogeneous, with inheritance patterns including autosomal dominant, autosomal recessive, and X-linked. X-linked inheritance is most common in hyper-IgM and agammaglobulinemia, primarily caused by variants in CD40LG and BTK respectively^8-9. For CVID, variants in TNFRSF13B are frequently identified¹⁰. Causative variants include both sequence variants and copy number variations. The diagnostic yield of this panel varies based on the clinical phenotype and specific PAD. Overall, a genetic diagnosis could be made in 24.7% of the investigated patients¹¹.

All genetic tests have limitations. Please refer to our Test Methods page for limitations relevant to this methodology.

The analytical sensitivity of the PGxome platform has been validated at >99% for single nucleotide variants, >95% for indels <49 bp, and >99% for CNV ≥3 exons in size. Sensitivity is reduced in regions with repetitive elements or paralogy.

The analytical sensitivity of the PGnome platform has been validated at >99% for sequence variants and >99% for structural variants (SV) 1kb-10Mb in size. Sensitivity is reduced in regions with repetitive elements or paralogy.

PGxome® platform: Capture and amplification based Next Generation Sequencing (NGS) is used to sequence the coding regions of nearly all genes and immediate flanking non-coding DNA (± 10 bp) in all available transcripts along with other non-coding regions harboring known disease-causing variants. Results are filtered to defined genes in panel. Reportable variants include both sequence variants and NGS-based detection of copy number variants (CNVs).

PGnome® platform: PCR-free Next Generation Sequencing (NGS) is used to sequence the coding regions of nearly all genes as well as intronic and intergenic regions. Detailed variant analysis and interpretation is focused on the coding exons and ± 10 bp into introns. Genomic variants outside of these coding regions are not investigated unless warranted (for example, if a gene of interest is highlighted by the provider, or if a single-hit pathogenic variant is found in a recessive gene). Results are filtered to defined genes in panel. Reportable variants include sequence variants; NGS-based detection of structural variants (SV), including copy number variants (CNVs) and inversions; and repeat expansion variants in currently available relevant genes.

Variants not meeting our quality threshold through NGS alone are confirmed with an orthogonal method, including but not limited to Sanger and array.

Variants which are classified as pathogenic, likely pathogenic, risk, or variant of uncertain significance will be analyzed and those that are considered to have a known or potential association with the provided patient indication(s) will be reported.