High-throughput immunogenetics reveals a lack of physiological T cell clusters in patients with autoimmune cytopenias

Autoimmune cytopenias (AIC) such as immune thrombocytopenia or autoimmunehemolytic anemia are claimed to be essentially driven by a dysregulated immunesystem. Using next-generation immunosequencing we profiled 59 T and B cellrepertoires (TRB and IGH) of 25 newly diagnosed patients with primary or secondary(lymphoma-associated) AIC to test the hypothesis if these patients present adisease-specific immunological signature that could reveal pathophysiological clues andeventually be exploited as blood-based biomarker. Global TRB and IGH repertoiremetrics as well as VJ gene usage distribution showed uniform characteristics for alllymphoma patients (high clonality and preferential usage of specific TRBV- and TRBJgenes), but no AIC-specific signature. Since T cell immune reactions toward antigens areunique and polyclonal, we clustered TCRb clones in-silico based on target recognitionusing the GLIPH (grouping of lymphocyte interactions by paratope hotspots) algorithm.This analysis revealed a considerable lack of physiological T cell clusters in patientswith primary AIC. Interestingly, this signature did not discriminate between the differentsubentities of AIC and was also found in an independent cohort of 23 patients with activeautoimmune hepatitis. Taken together, our data suggests that the identified T cell clustersignature could represent a blood biomarker of autoimmune conditions in general andshould be functionally validated in future studies.