Repertoire “gaps” in antiphospholipid syndrome

Case study
Using the IgOme to reveal restriction in the autoimmune IgM repertoire.

Project · Case study

Using the IgOme to reveal restriction in the autoimmune IgM repertoire.

Problem

Can the functional IgM reactivity landscape reveal a mechanism of autoimmune diseases, beyond a list of autoantigens?

Method

Represent the IgOme as a graph of mimotope sequences linked by a shared subsequence. The optimal cutoff (5 of 7 residues) is determined from a set of mimotopes grouped by the panning mAbs that recognize them. Graph clusters are used to estimate differential expression across large cross-reactivity classes1.

Result & open questions

The patient IgM repertoire shows signs of restriction — “gaps” relative to healthy individuals. Open: are gaps cause or consequence?

Related: Graph representations

References

1.
Pashova, S. et al. Restriction of the global IgM repertoire in antiphospholipid syndrome. Frontiers in Immunology 13, 865232 (2022).