High-Throughput Immunogenetics Reveals a Lack of Physiological T Cell Clusters in Patients With Autoimmune Cytopenias

TY - JOUR

T1 - High-Throughput Immunogenetics Reveals a Lack of Physiological T Cell Clusters in Patients With Autoimmune Cytopenias

AU - Simnica, Donjete

AU - Schliffke, Simon

AU - Schultheiß, Christoph

AU - Bonzanni, Nicola

AU - Fanchi, Lorenzo F

AU - Akyüz, Nuray

AU - Gösch, Barbara

AU - Casar, Christian

AU - Thiele, Benjamin

AU - Schlüter, Janina

AU - Lohse, Ansgar W

AU - Binder, Mascha

PY - 2019

Y1 - 2019

N2 - Autoimmune cytopenias (AIC) such as immune thrombocytopenia or autoimmune hemolytic anemia are claimed to be essentially driven by a dysregulated immune system. Using next-generation immunosequencing we profiled 59 T and B cell repertoires (TRB and IGH) of 25 newly diagnosed patients with primary or secondary (lymphoma-associated) AIC to test the hypothesis if these patients present a disease-specific immunological signature that could reveal pathophysiological clues and eventually be exploited as blood-based biomarker. Global TRB and IGH repertoire metrics as well as VJ gene usage distribution showed uniform characteristics for all lymphoma patients (high clonality and preferential usage of specific TRBV- and TRBJ genes), but no AIC-specific signature. Since T cell immune reactions toward antigens are unique and polyclonal, we clustered TCRβ clones in-silico based on target recognition using the GLIPH (grouping of lymphocyte interactions by paratope hotspots) algorithm. This analysis revealed a considerable lack of physiological T cell clusters in patients with primary AIC. Interestingly, this signature did not discriminate between the different subentities of AIC and was also found in an independent cohort of 23 patients with active autoimmune hepatitis. Taken together, our data suggests that the identified T cell cluster signature could represent a blood biomarker of autoimmune conditions in general and should be functionally validated in future studies.

AB - Autoimmune cytopenias (AIC) such as immune thrombocytopenia or autoimmune hemolytic anemia are claimed to be essentially driven by a dysregulated immune system. Using next-generation immunosequencing we profiled 59 T and B cell repertoires (TRB and IGH) of 25 newly diagnosed patients with primary or secondary (lymphoma-associated) AIC to test the hypothesis if these patients present a disease-specific immunological signature that could reveal pathophysiological clues and eventually be exploited as blood-based biomarker. Global TRB and IGH repertoire metrics as well as VJ gene usage distribution showed uniform characteristics for all lymphoma patients (high clonality and preferential usage of specific TRBV- and TRBJ genes), but no AIC-specific signature. Since T cell immune reactions toward antigens are unique and polyclonal, we clustered TCRβ clones in-silico based on target recognition using the GLIPH (grouping of lymphocyte interactions by paratope hotspots) algorithm. This analysis revealed a considerable lack of physiological T cell clusters in patients with primary AIC. Interestingly, this signature did not discriminate between the different subentities of AIC and was also found in an independent cohort of 23 patients with active autoimmune hepatitis. Taken together, our data suggests that the identified T cell cluster signature could represent a blood biomarker of autoimmune conditions in general and should be functionally validated in future studies.

U2 - 10.3389/fimmu.2019.01897

DO - 10.3389/fimmu.2019.01897

M3 - SCORING: Journal article

C2 - 31497012

VL - 10

SP - 1897

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

ER -