Quantitative B-lymphocyte deficiency and increased TCRγδ T-lymphocytes in acute infectious spondylodiscitis

TY - JOUR

T1 - Quantitative B-lymphocyte deficiency and increased TCRγδ T-lymphocytes in acute infectious spondylodiscitis

AU - Haugaard, Anna K

AU - Marquart, Hanne V

AU - Kolte, Lilian

AU - Ryder, Lars Peter

AU - Kehrer, Michala

AU - Krogstrup, Maria

AU - Dragsted, Ulrik B

AU - Dahl, Benny

AU - Gjørup, Ida E

AU - Andersen, Åse B

AU - Garred, Peter

AU - Nielsen, Susanne D

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Acute infectious spondylodiscitis (AIS) is a serious infection of the spine with rising incidence and a mortality of 3-6%. The role of the immune system in AIS is largely unknown. We performed extensive B and T-lymphocyte phenotyping in patients with AIS at diagnosis and after treatment cessation. In this prospective multicentre study, flow cytometric analysis of T and B-lymphocyte subsets was performed in 35 patients at diagnosis and 3 months after treatment cessation. We additionally analysed levels of immunoglobulins and IgG subclasses, serum level and genetic variants of mannose-binding lectin, and somatic hypermutation. A total of 22 (61%) patients had B-lymphocytes below reference limit at baseline, persisting in 7 (30%) patients at follow-up. We found a lower proportion of CD19 + CD27 + IgD+ marginal zone B-lymphocytes and a higher proportion of γδ+ T-lymphocyte receptors compared with controls at both time points. Immunoglobulin levels were elevated at baseline compared to follow-up, and not associated with absolute B-lymphocyte count. In conclusion, a large proportion of AIS patients presented with profound B-lymphocyte deficiency, only partly reversible at follow-up. Identification of immune dysfunction related to AIS may allow for future targeted therapeutic interventions to restore host immunity.

AB - Acute infectious spondylodiscitis (AIS) is a serious infection of the spine with rising incidence and a mortality of 3-6%. The role of the immune system in AIS is largely unknown. We performed extensive B and T-lymphocyte phenotyping in patients with AIS at diagnosis and after treatment cessation. In this prospective multicentre study, flow cytometric analysis of T and B-lymphocyte subsets was performed in 35 patients at diagnosis and 3 months after treatment cessation. We additionally analysed levels of immunoglobulins and IgG subclasses, serum level and genetic variants of mannose-binding lectin, and somatic hypermutation. A total of 22 (61%) patients had B-lymphocytes below reference limit at baseline, persisting in 7 (30%) patients at follow-up. We found a lower proportion of CD19 + CD27 + IgD+ marginal zone B-lymphocytes and a higher proportion of γδ+ T-lymphocyte receptors compared with controls at both time points. Immunoglobulin levels were elevated at baseline compared to follow-up, and not associated with absolute B-lymphocyte count. In conclusion, a large proportion of AIS patients presented with profound B-lymphocyte deficiency, only partly reversible at follow-up. Identification of immune dysfunction related to AIS may allow for future targeted therapeutic interventions to restore host immunity.

U2 - 10.1038/s41598-018-33318-w

DO - 10.1038/s41598-018-33318-w

M3 - Journal article

C2 - 30310085

SN - 2045-2322

VL - 8

JO - Scientific Reports

JF - Scientific Reports

M1 - 15174

ER -