Progress and challenges in the use of blood biomarkers in relapsing polychondritis

Abstract

Relapsing polychondritis (RP) is a rare inflammatory disease with significant individual heterogeneity that involves systemic organs. The diagnosis of RP mainly depends on the clinical manifestations; currently, there are no molecular biomarkers routinely evaluated in clinical practice. Biomarkers have diagnostic or monitoring values and can predict response to treatment or the disease course. Over the years, many biomarkers have been proposed to facilitate diagnosis and prognosis. Unfortunately, ideal biomarkers to diagnose RP have not yet been discovered. Most of the molecular biomarkers in RP are immunological biomarkers, with autoantibodies and proteins related to cartilage damage in the blood being the most common. Alterations in some genes (HLA typing and UBA1 somatic mutation) were detected in patients with RP, which could serve as a potential biomarker for the diagnosis of RP. Moreover, proinflammatory cytokine and lymphocyte levels, and certain laboratory tests, have certain values of RP diagnosis and disease activity assessment but lack specificity and sensitivity. This review describes the different types of biomarkers and their clinical correlation with respect to the diagnosis of RP and disease activity. Research on biomarkers and disease pathology is ongoing to identify the ideal biomarkers that are sensitive and specific for RP.

Autoimmunity and Autoinflammation: Relapsing Polychondritis and VEXAS Syndrome Challenge

“…Although the etiopathogenic mechanisms of RP are still incompletely understood, the data that we have so far support the important role of a predisposing genetic background on which trigger factors act, thus initiating autoimmune phenomena [15]. There are no data to support the hereditary transmission of the disease [1].…”

“…Numerous studies have focused on analyzing genetic susceptibility in RP, with the role of human leukocyte antigen (HLA) being recognized in the occurrence of autoimmune diseases [15]. HLA-DR4 is an allele that confers a major risk of RP occurrence, but there is no predominance of a certain subtype of DR4 alleles in this condition [16,17].…”

“…Recently, a syndrome was described that occurs only in men and that includes inflammation of the cartilage, blood vessels and skin, as well as hematological manifestations [15]. This condition is called VEXAS syndrome, with the acronyms referring to its main characteristics: vacuoles, E1 enzyme, X-linked, autoinflammatory manifestations and somatic manifestations [15,22]. It is very possible that more than half of the individuals diagnosed with RP who have associated myelodysplastic syndrome actually have VEXAS syndrome [22].…”

Innate immune responses in Behçet disease and relapsing polychondritis

“…In the clinical manifestations, respiratory and auricular involvement, which are two key hallmark features of RP, are recognized in 40–67% and 85–90% of patients with RP, respectively, at the latest follow-up ( 10–13 ). Tracheobronchial chondritis is increasingly recognized as distinct from other pathogenic complications ( Figure 2B ) ( 99 , 100 ). Certainly, patients with RP with respiratory involvement have progressive disease compared to those with auricular involvement ( 101 ).…”