Tuesday, 19 Nov 2019

You are here

Monocyte Patrolling Contributes to Lupus Glomerulonephritis

Systemic lupus erythematosus (SLE) is an autoimmune disease with a propensity to develop glomerulonephritis (47-70%) or end-stage kidney disease despite therapy.

Hallmarks of the disease are the appearance of immune complexes (IC) containing autoreactive Abs and TLR-activating nucleic acids, whose deposition in kidney glomeruli is suspected to promote tissue injury and glomerulonephritis (GN).

The pathogenesis of lupus GN was investigated using 3 different mouse models of SLE and SLE patients all of whom demonstrated glomerular accumulation of patrolling monocytes (PMos), a cell type with an emerging key function in vascular inflammation.

Lupus nephritis is considered an immune complex–mediated (IC-mediated) form of GN. Although the relevance of ICs in lupus nephritis is debated, IC deposition cand lead to complement-mediated cytotoxicity and end-organ damage.

ICs may also contribute to GN by activating Toll-like receptors (TLR), including TLR7, TLR8, and TLR9, on B cells, further contributing the tissue damage and inflammation. It is possible that the therapeutic efficacy of antimalarials are mediated by the prevention of TLR activation.

A potential B cell–independent mechanism for lupus GN is supported by more than 50 genetic SLE susceptibility loci with functions outside the adaptive immune system. One such susceptibility locus for SLE and lupus GN TNIP1 (TNFAIP3-interacting protein 1; also referred to as ABIN1, A20-binding inhibitor of NF-κB activation 1).  ABIN1 is a negative regulator of the TNFR, TLR, and IL-17R pathways, and, ABIN1-deficient mice develop a systemic lupus-like disease that includes major characteristics of human SLE, including autoreactive Abs and severe GN.

Studies reported in the Journal of Clinical Investigation have shown that monocyte-specific deletion of ABIN1, promoted kidney disease, whereas selective elimination of patrolling monocytes provided protection against GN.

Patrolling monocytes (PMos) are one of the two monocytes found in the peripheral blood (PB), PMos numbers are increased in the PB and kidney glomeruli of lupus.  Investigators have shown that PMos are capable of mediating tissue injury in lupus-nephritis based on studies done to characterize GN in ABIN1-deficient mice and 2 additional independent lupus models. 

These data identify TLR-activated PMos as the principal component of an intravascular process that contributes to glomerular inflammation and kidney injury. based on the SLE susceptibility locus TNFAIP3-interacting protein 1 (TNIP1, also known as ABIN1).



The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

Part 1:  The “P” in Prednisone stands for Poison...and Other Pearls

Everyone has life hacks.  Years of experience and doing the same things repetitively allow us to figure out little tricks to make life easier. A rat in a maze, finding itself at a dead end, will back up and search for a clearing. If this rat encounters its neighbor, it will transmit that information so the second rat won’t make the same mistake.

Protective Effects of ASA and Vasodilators in Systemic Sclerosis

A large cohort study suggests that the use of vasodilators and aspirin (ASA) in systemic sclerosis (SSc) may yield favorable  cardiovascular outcomes.

Myositis Patients at High Risk of Opportunistic Infections

Among patients with systemic rheumatic diseases, the highest incidence of opportunistic infections was seen in those with polymyositis/dermatomyositis (PM/DM), Taiwanese researchers found.

Warfarin Superior to Xarelto in Antiphospholipid Syndrome

A 3 year, multicenter, European, study shows that rivaroxaban was inferior to warfarin in preventing thrombosis in patients with antiphospholipid syndrome (APS) according to the Annals of Internal Medicine. Thus despite the inconvenience of warfarin, it remains the best option for patients with APS.

Declining Trends in Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis Mortality in the USA

Annals of Internal Medicine reports that age-adjusted mortality rates for antineutrophil cytoplasmic autoantibody–associated vasculitides (AAV) have improved over time - with a decline of nearly 2 percent per year in the United States from 1999 to 2017. Nevertheless, long-term outcomes continue to lag behind mortality rates of the general population.