COMMENTARY

Current and Novel Vasculitis Biomarkers

Tejas P. Desai, MD

Disclosures

January 06, 2017

Current and Novel Biomarkers in Anti-neutrophil Cytoplasm-Associated Vasculitis

Draibe JB, Fulladosa X, Cruzado JM, Torras J, Salama AD
Clin Kidney J. 2016;9:547-551

In the past, patients diagnosed with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have almost universally had fatal outcomes. Even though advances in the past 20 years have almost eliminated such fatalities, the disease still provokes apprehension among nephrology providers and their patients. Perhaps that effect is due to our unfamiliarity with AAV, given its relative rarity in the pantheon of diseases that we treat. Or perhaps it stems from our persistently incomplete understanding of the disease.

A prime source of confusion originates from our use of the key clinical marker used to diagnose AAV: the ANCA titer. The titer has been a diagnostic boon in the early identification of AAV. In recent years, several scientific publications have touted its utility beyond diagnostics. ANCA titers are commonly used to prognosticate disease severity and to identify recurrence of the disease—although depending on whom you ask, the ANCA titer should be used only for diagnostic purposes (Figure). This unresolved debate adds to the clinician's uncertainty in how best to manage patients with this rare disease.

Figure 1. The ANCA titer. Image courtesy of Tejas Desai, MD

While this debate plays out in the scientific literature, a new group of researchers are searching for novel, multipurpose biochemical markers (ie, valuable as a diagnostic, prognostic, and surveillance tool). Finding a marker, or even a combination of markers, that can achieve this hat trick is a priority for a number of research laboratories. In this review, we look at potential contenders for simultaneous diagnosis, prognostication, and surveillance of AAV.

LAMP-2

Lysosome-associated membrane protein 2 (LAMP-2) is expressed in endothelial cells and neutrophils. Unsurprisingly, antibodies against LAMP-2 are commonly found in patients with pauci-immune glomerulonephritis. The primary attractiveness of LAMP-2 is that it is found in patients with biopsy-proven ANCA-negative pauci-immune glomerulonephritis. Moreover, LAMP-2 antibody titers fall during disease quiescence and rise during disease recurrence. Perhaps the biggest hurdle that LAMP-2 faces at this time is that clinically available testing is not yet available.

Moesin

Moesin is a protein that links actin to the plasma membrane. Scientists in Japan showed that antimoesin antibody titers are elevated in AAV and are proportional to the severity of disease.[1] The biggest hurdle that moesin faces is that it needs to be tested in a more heterogeneous population (data come mostly from the East Asian population).

B-cell Regulators and CD8+ T Cells

Researchers are actively looking at the presence/absence and number of B-cell regulators (eg, CD25+, CD5+, and CD24+/-/38+-) and CD8+ T cells. These cells are either abundantly or sparsely found in patients with AAV. Indeed, the notion that B cells have an integral pathogenetic role in developing AAV was strengthened by the use of rituximab in the RAVE[2] and RITUXIVAS trials.[3]

Urinary Biomarkers

The blood alone does not hold the key for identification of AAV. The urinary biomarkers monocyte chemoattractant protein 1 (MCP-1) and CD163 are the ones to watch.

MCP-1 is a chemokine that attracts monocytes to areas of inflammation. Early data show a very high positive likelihood ratio of having the disease (nearly 8.5 with an AUC of 0.93) and a near zero negative likelihood ratio (0.07). CD163 is a urine-soluble protein that is shed by monocytes and macrophages during periods of intense inflammation. In some of the more recent studies of CD163, the positive likelihood ratio approaches 21 (20.8).[4]

The two-pronged approach of AAV research, identification and treatment, are active and moving forward at an exciting pace. Hopefully, both arms will reach fruitful conclusions that help clinicians better understand and treat this rare condition.

Now it's your turn. Tell us what excites you about the research being conducted. What do you think will be the next best biomarker (or combination of biomarkers) that can diagnose, prognosticate, and monitor AAV disease activity? Use the comments section below to share your thoughts.

Abstract

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