Low Levels of Th17 Cells Linked to Developing RA

Th17 cell levels may be predictive of rheumatoid arthritis (RA) development, particularly among patients who test negative for anti-citrullinated protein antibodies (ACPA), according to research published in Rheumatology.

Researchers sought to determine whether a novel epigenetic quantitative polymerase chain reaction (qPCR), used to quantify Th17 T-cell subsets, can serve as a diagnostic biomarker to aid in the diagnosis of RA.

Using data from the Leeds Inflammatory Arthritis Disease Continuum, researchers selected 172 disease-modifying antirheumatic drug-naive patients with early inflammatory arthritis; 49 health controls were also recruited.

Investigators used the Th17 qPCR assay to measure the presence of Th17 cells in study participants. Cell frequency was similar in healthy controls, patients with nonpersistent arthritis, and patients with undifferentiated arthritis. Participants with RA at recruitment and those with inflammatory arthritis that progressed to RA over 24 months had significantly fewer Th17 cells compared with the other groups (P <.01). A direct comparison of patients with and without RA, found that the frequency of Th17 cells was “significantly reduced” (P <.0001). Additionally, the presence of ACPA and/or rheumatoid factor was not associated with pronounced differences in Th17 cells (P =.166 in the overall cohort; P =.355 in the RA subgroup).

In a multivariate regression analysis, unadjusted odds ratios (ORs) confirmed an association between RA and 5 parameters:

• ACPA;
• swollen joint count;
• C-reactive protein;
• Th17; and
• the disease activity score in 28 joints was also linked (P =.002).

In a combined regression model, ORs “placed Th17 frequencies as the best predictor of RA” (OR 1.32e⁷).

Among patients whose test results were ACPA-negative, a Th17/clinical model performed relatively well compared with a clinical-only model (73% correct prediction), with swollen joint count continuing to contribute to the prediction.

Researchers were able to use a surrogate phenotype to quantify circulating Th17 cells, confirming a “significant difference between [patients with RA and healthy controls],” with decreased frequency of Th17 in the RA group. On an individual basis, this result was of limited value. However, researchers further examined these results and found that patients with RA express “significantly more CXCR4” chemokine receptors than healthy controls (11 vs 15, respectively). Per the researchers, “the differential expression of CXCR4 on RA Th17 is a novel finding.”

“Altogether, these data … confirm that epigenetic alterations are involved early in the disease process at the time of clinical symptom development and predict an evolution towards RA,” the researchers concluded. “Our data also suggest a further role for TH17 cell quantification along the [inflammatory arthritis] continuum possibly from pre-clinical, at risk stages.”

The researchers of the study concluded that this “offers a validated tool to classify RA early … and may also be of further use across the [inflammatory arthritis] continuum for predicting response to conventional and biological therapy.”

Disclosures: Drs Olek, Samans, and Raschke are employees of Epionits GmbH, Division of Precision for Medicine.

Reference
Burska AN, Thu A, Parmar R, et al. Quantifying circulating Th17 cells by qPCR: potential as diagnostic biomarker for rheumatoid arthritis [published online May 12, 2019]. Rheumatology. doi: 10.1093/rheumatology/kez162