The following is a summary of “Immunoglobulin repertoire restriction characterizes the serological responses of patients with predominantly antibody deficiency,” published in the JULY 2023 issue of Allergy & Immunology by Troelnikov, et al.
The most prevalent category of inborn immune system defects is mostly antibody deficit, predominantly antibody deficiency (PAD), defined by decreased production of necessary antibody diversity and quantity. Clinically, responses are assessed through vaccination responses, which are crucial for PAD diagnoses. However, traditional serological measures cannot fully reveal the composition of the antibody repertoire. Modern mass spectrometry–based proteomics (MS-proteomics) can elucidate the molecular features of specific antibody repertoires, addressing diagnostic limitations in vaccinology. For a study, researchers sought to evaluate serum antibody responses in PAD patients following vaccination with a neo-antigen (severe acute respiratory syndrome coronavirus-2 vaccination) using MS-proteomics.
Serological responses in PAD individuals and healthy controls (HCs) were assessed after severe acute respiratory syndrome coronavirus-2 vaccination using anti-S1 subunit ELISA and neutralization assays. Purified anti-S1 subunit IgG and IgM were profiled using MS-proteomics to analyze IGHV subfamily usage and somatic hypermutation.
Twelve vaccine-responsive patients with PAD were recruited in the study, along with 11 matched vaccinated healthy controls (HCs). The results showed that neutralization and endpoint anti-S1 titers were lower in PAD than HCs. Additionally, all PAD subjects exhibited restricted anti-S1 IgG antibody repertoires, utilizing <5 IGHV subfamilies (median: 3; range 2-4), while the 11 HC subjects used ≥5 more subfamilies (P < 0.001). Notably, IGHV3-7 utilization was significantly less common in PAD patients than HCs (2 of 12 vs 10 of 11; P = 0.001). However, there were no significant differences in amino acid substitutions due to somatic hypermutation per subfamily between the two groups. Regarding anti-S1 IgM, it was present in 64% of HCs and 50% of PAD patients, and the difference between the cohorts was not statistically significant.
The study revealed the breadth of anti-S1 antibodies elicited by vaccination at the proteome level and identified stereotypical restriction of IGHV utilization in the IgG repertoire of PAD patients compared to HCs. Despite uniformly pauci-clonal antibody repertoires, some PAD patients generated potent serological responses, indicating a limitation of traditional serological techniques. The findings suggested that IgG repertoire restriction is a key feature of antibody repertoires in PAD.
Source: jacionline.org/article/S0091-6749(23)00365-2/fulltext