A lymph gland biopsy, Do you think you would do this? It tells us the blood is different

Recently I have had to sit through some dreary EAE studies, where the animal studies were justified by saying it was impossible to know what happens in lymph nodes and bone marrow. in humans I would say do some reading and you will find that the animal studies added nothing to what we know happens in humans.

Learning from other autoimmunities to understand targeting of B cells to control multiple sclerosis. Baker D, Pryce G, Amor S, Giovannoni G, Schmierer K. Brain. 2018;141:2834-2847.

People have their tonsils (a lymph gland) removed, they even have their spleens removed sometimes, but however, I came across this paper and it further casts doubt on what the EAEers were saying.

This talks about a technique to biopsy lymph nodes as well as getting blood. I thought this was interesting and a powerful tool to answer questions. It uses ultrasound to guide putting a needle into a lymph gland. I have removed the disease related aspects of the paper as this wan’t MS, but it could answer a few questions. It’s open access and you can read this.

It clearly shows what we know from animal studies in that the blood does not reflect what’s in the the lymph node. It says there are a lot more memory cells in the lymphoid tissue than the blood.

But it also suggests that some antibodies may struggle to clear out the lymph glands because many of them depend on natrual killer cells to deplete and there are vanishing few in the lymph glands, therefore antibodies like alemtuzumab and ocrelizumab may not work as well there as in the blood.

Would you be willing to have such a biopsy if you were taking these treatments.

Phenotypic Analysis of Human Lymph Nodes in Healthy Individuals by Flow Cytometry. Yang JHM, Khatri L, Mickunas M, Williams E, Tatovic D, Alhadj Ali M, Young P, Moyle P, Sahni V, Wang R, Kaur R, Tannahill GM, Beaton AR, Gerlag DM, Savage COS, Napolitano Rosen A, Waldron-Lynch F, Dayan CM, Tree TIM. Front Immunol. 2019 Oct 31;10:2547

Background: Ultrasound guided sampling of human lymph node (LN) combined with advanced flow cytometry allows phenotypic analysis of multiple immune cell subsets. These may provide insights into immune processes and responses to immunotherapies not apparent from analysis of the blood. Methods: Ultrasound guided inguinal LN samples were obtained by both fine needle aspiration (FNA) and core needle biopsy. Peripheral blood mononuclear cells (PBMC) were obtained on the same occasion. Samples were transported same day to the central laboratory and analyzed by multicolour flow cytometry. Results: LN sampling was well-tolerated and yielded sufficient cells for analysis in 95% of cases. We demonstrated clear enrichment of CD8⁺ naïve, FOXP3⁺ Treg, class-switched B cells,  and plasmacytoid dendritic cells (DC) in LNs as well as CD4⁺ T cells of the Th2 phenotype. Conventional NK cells were virtually absent from LNs as were Th22 and Th1Th17 cells. Paired correlation analysis of blood and LN in the same individuals indicated that for many cell subsets, especially those associated with activation: such as CD25⁺ and proliferating (Ki67⁺) T cells, activated follicular helper T cells and class-switched B cells, levels in the LN compartment could not be predicted by analysis of blood.

Conclusions: LN sampling in humans is well-tolerated. We provide the first detailed “roadmap” comparing immune subsets in LN vs. blood emphasizing a role for differentiated effector T cells in the blood and T cell regulation, B cell activation and memory in the LN. For many subsets, frequencies in blood, did not correlate with LN, suggesting that LN sampling would be valuable for monitoring immuno-therapies where these subsets may be impacted