Changes in Circulating Immune Cells in AAV Linked to Kidney Damage

Ashraf Malhas, PhD avatar

by Ashraf Malhas, PhD |

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Although certain immune cells are present at lower levels in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), it is due to non-specific renal injury rather than the disease itself, study shows.

The study, “Alterations in circulating lymphoid cell populations in systemic small vessel vasculitis are non-specific manifestations of renal injury,” was published in the journal Clinical and Experimental Immunology.

AAV refers to a group of three rare diseases: Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). It is characterized by inflammatory cell infiltration and the death of blood vessel walls. Current evidence suggests the underlying disease mechanism is driven by autoantibodies that are present in most cases of GPA and MPA and in approximately 35 percent of EGPA cases.

Certain immune cells, such as mucosal associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells, γδ T-cells, and innate lymphoid cells (ILCs), play a significant role in auto-inflammatory and autoimmune diseases.

Researchers at the Trinity Translational Medicine Institute, in Dublin, Ireland, assessed the frequencies and absolute numbers of these and other immune cells in the blood from a group of AAV patients and controls.

The study involved 38 AAV patients, 10 healthy people, and 14 patients with matched ages and kidney function, but without any auto-immune disease. Samples from the AAV patients were obtained with and without immunosuppressive treatment, and in active and remission phases.

AAV patients had lower levels of circulating ILC2 and MAIT cells compared to healthy controls, but not when compared to disease controls with renal abnormalities. This indicates that low levels of these immune cells cells are due to kidney involvement rather than AAV itself.

This led authors to conclude that the result is important because it highlights “the importance of including disease control groups in phenotyping studies.”

No differences in the levels of iNKT and γδ T-cells were observed between AAV patients and control subjects, irrespective of the disease phase. Examination of the levels of other lymphocytes and monocytes generated similar results. However, the levels of B-cells were significantly lower in AAV patients in remission compared to those with active disease or controls.

ILC2, γδ T-cells, and iNKT cells are involved in the production of pro-inflammatory proteins such as interleukins 4, 5, and 13 (IL-4, IL-5, and IL-13), which are elevated in EGPA patients. However, the results of the current study suggest that the levels of these proteins in EGPA patients is not a result of higher numbers of the cells that produce them.