Sixty stool samples from 22 APS patients were compared at baseline, four and eight weeks with 13 samples from six controls with non-autoimmune thrombophilic conditions, and 49 samples from 19 healthy individuals. Stool DNA and peripheral blood mononuclear cell (PBMC) proliferation to the auto-antigen β2 GPI were measured.
The APS patients’ PBMCs responded preferentially to β2 GPI compared to the controls, said Dr. Kriegel. Their fecal microbiomes showed decreased levels of Bilophila and higher levels of Slackia. In addition, 59% of the APS patients were positive for anti-domain I (anti-DI) antibodies, compared to none of the controls. Anti-DI IgG positivity significantly correlated to increased Slackia and decreased Butyricimonas.
Slackia can secrete cardiolipin, a target lipid in APS that could promote autoreactivity against the major B cell epitope in β2 GPI. Positivity for anti-DI IgG is significantly correlated to increased Slackia. In APS patients, β2 GPI is often bound by phospholipids that make it more immunogenic. Thrombosis risk is much higher in people with these antibodies, so these findings are clinically relevant, he said.
Genetic Signs of Anti-TNF Response
Single-cell gene expression signatures in the pretreatment blood serum of rheumatoid arthritis patients may help rheumatologists predict response to anti-TNF therapy, according to a new study by researchers at the Mayo Clinic.3
“We are beginning to understand what’s happening at the cellular level in patients who do not respond to TNF inhibitors,” said Theresa L. Wampler Muskardin, MD, a rheumatologist and lead author of the study. In their previous research, they found that patients with an interferon (IFN) β/α ratio of greater than 1.3 predicted non-response to anti-TNF therapy. Next, they wanted to identify differences in select gene expression between responders and non-responders.
Using single-cell expression analysis, they isolated single classical and non-classical blood-derived monocytes in the pretreatment blood serum of 15 seropositive RA patients: Six with an IFN-β/α ratio of greater than 1.3 and nine with a ratio of less than 1.3.
[Genetic] research may one day lead to a blood test ‘that could tell us whether a patient would respond to treatment before it is tried, which would expedite achieving control over the disease & allow us to avoid the cost & risk of exposing patients to medicines to which they’re not going to respond.’ —Dr. Muskardin
JAK1 and IL1A expression were retained in models for the prediction of treatment response for all monocytes. TLR9, STAT1 and FCER were retained in the prediction response model in classical monocytes alone. STAT2 and IFI27 were retained in the model in non-classical monocytes alone. Further study of monocyte subsets may reveal molecular differences that determine treatment response to TNFα inhibition in RA, and better understanding of mechanisms of the IFNβ/α ratio may help researchers locate other markers that point to therapy targets, she said. This research may one day lead to a blood test “that could tell us whether a patient would respond to treatment before it is tried, which would expedite achieving control over the disease and allow us to avoid the cost and risk of exposing patients to medicines to which they’re not going to respond,” she said.
Wnt-Inhibitor Promising for Knee OA
Patients with knee OA who received a single, intra-articular injection of SM04690, a Wnt-inhibitor, showed improved pain and function compared to placebo in a Phase I trial.4 Patients who had the therapy also either maintained their joint space width, a sign of slowed arthritis, or increased width, a potential sign of cartilage growth, said Yusuf Yazici, MD, chief medical officer of Samumed LLC, a biotech company in San Diego where the research was conducted.