Immunosuppressives Seen to Aid SSc-PAH Patient with Rare Antibody

A 62-year-old with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) was successfully treated with immunosuppressants and vasodilators, a case study reports.

The unusual antibody linked to her disease, called the anticentriole antibody, may also serve as a marker for the use of immunosuppressives in SSc-PAH patients with this antibody.

The study, “Successful Treatment of Pulmonary Arterial Hypertension in Systemic Sclerosis with Anticentriole Antibody,” was published in the journal Case Reports in Rheumatology. 

Systemic sclerosis (SSc), characterized by an overgrowth of connective tissue in the skin and a narrowing of blood vessels, can lead to multiple organ damage. SSc can also predispose patients to PAH; in fact, it is estimated that about 10% of all patients with SSc experience PAH.

Recommended treatments for SSc-PAH include vasodilators, like phosphodiesterase-5 inhibitors, endothelin receptor antagonists, prostacyclin analogs, and soluble guanylate cyclase stimulators.

Immunosuppressive therapy is usually not effective in SSc-PAH patients. However, clinical trials testing rituximab (brand name Rituxan, marketed by Genentech and Biogen), tocilizumab, and dimethyl fumarate (brand name Tecfidera, by Biogen) in this patient population are underway, and have shown some success.

Several case reports have also found that some SSc-PAH patients are responsive to these therapies.

“However, it still remains unclear what kind of clinical features or biomarkers are useful to identify SSc-PAH patients on whom immunosuppressive therapies are effective,” the researchers wrote.

People with SSc, an autoimmune disease, have various types of autoantibodies that mistakenly attack the body’s own tissues. Different types of autoantibodies are associated with different clinical presentations. One of these, the anticentriole antibody, is reported to be highly associated with PAH in patients with SSc.

Of note, centrioles are part of the centrosome, a structure that plays a central role in cell division.

Researchers at Tohoku University Graduate School of Medicine, in Japan, detail the case of an SSc-PAH patient with anticentriole antibodies who was successfully treated with vasodilators and immunosuppressive therapies.

The patient, a 62-year-old female, complained of difficulty breathing during physical exercise (exertional dyspnea) for two years, and severe swelling in her legs. Examinations of the heart revealed she had overload of the right side of the heart, but normal ejection fraction.

The patient also had high blood pressure in one of the valves of the right side of the heart (tricuspid regurgitation pressure gradient), and elevated mean pulmonary arterial pressure (mPAP). Her pulmonary tests suggested impaired lung function.

She was diagnosed with PAH group 1 and subsequently with SSc. Staining assays detected unusual anticentriole antibodies.

Initially, treatment included oral vasodilators [beraprost and Adempas (riociguat)], and diuretics (azosemide, spironolactone, and tolvaptan). Because her dyspnea did not completely ease with the vasodilators, and she was positive for anticentriole antibodies, doctors started her on immunosuppressive therapy with prednisolone and intravenous cyclophosphamide.

After two months, the patient’s mPAP decreased (from 47 to 33 mmHg), and her physical ability, measured via the 6-minute walk distance (6MWD) test, also improved (from 418 meters to 480 meters). The anticentriole antibodies disappeared.

The patient was then started on another immunosuppressive therapy, azathioprine, and prednisolone was gradually decreased and maintained at a lower dose. A new vasodilator, Uptravi (selexipag), was added to the treatment. “PAH has been well controlled using these treatments,” the researchers wrote.

“To the best of our knowledge, this is the first report of an SSc-PAH patient with anticentriole antibody, who was successfully treated. In this case, the hemodynamics of PAH were further improved and stably maintained after the induction of immunosuppressive therapies,” the researchers wrote.

The presence of anticentriole antibody in the context of SSc-PAH could mean that the condition is immune-mediated, the researchers said, and this antibody may be a valuable biomarker in determining those patients most likely to benefit from immunosuppressive treatment.

“The presence of the anticentriole antibody is rare; however, it may be a useful biomarker that affects diagnostic and therapeutic strategies for SSc-PAH,” the team suggested.