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Testing for Th/To Antibodies May Help in Scleroderma Management

— Test identifies patients at high risk for pulmonary hypertension

Ƶ MedicalToday
A computer rendering of antibodies.

Detection of certain auto-antibodies flagged patients with scleroderma (also known as systemic sclerosis) who were especially likely to develop pulmonary hypertension over long-term follow-up, a single-center study indicated.

Some 38% of patients with limited cutaneous scleroderma testing positive for so-called anti-Th/To antibodies went on to be diagnosed with pulmonary hypertension, versus 15% of similar patients without these antibodies, reported Robyn T. Domsic, MD, MPH, of the University of Pittsburgh Medical Center (UPMC), and colleagues.

Mortality was also higher in the antibody-positive patients, they noted in .

"Patients presenting with limited skin involvement should be tested for Th/To antibody," the group wrote. "If present, careful monitoring for [pulmonary hypertension] is warranted."

These antibodies target a complex of 12 nuclear antigens, including RNA-processing enzymes and other proteins. UPMC researchers have been following the question of their role in scleroderma-related pathology for more than 30 years. In 1990, Thomas Medsger Jr., MD, and a colleague of 371 UPMC patients with scleroderma, in which many of those with minimal dermal manifestations were positive for anti-Th antibodies.

Moreover, that subgroup seemed to have a unique symptom set, including "puffy fingers, small bowel involvement, and hypothyroidism, and a significantly lower frequency of arthralgia and/or arthritis." A from the group looked more specifically at anti-Th/To antibodies, with similar findings plus a higher rate of interstitial lung disease and pulmonary arterial hypertension.

The previous UPMC studies, as well as some from other researchers, documented these associations in cross-sectional analyses, often from testing performed on new patients. But, as Domsic and colleagues explained in the current publication (including Medsger as a co-author), long-term outcomes in these patients remain unknown.

Hence, they went back to patients seen at their scleroderma referral center from 1980 to 2015 -- a total of 3,613 -- to examine what happened to them over time. These patients included 204 who had tested positive for anti-Th/To antibodies. Domsic and colleagues also pulled records for the next two scleroderma patients testing negative after each positive case, for a total of 408 controls. Median follow-up after testing was 6.1 years (interquartile range 2.4-12.7).

Nearly all (97%) of the antibody-positive patients, called "cases" in the manuscript, had the limited-skin-involvement subtype, whereas this was the diagnosis for 56% of antibody-negative controls. (Of potential interest, median time from symptom onset to their first UPMC visit was 7.9 years for cases versus 3.3 years for controls [P<0.0001]. Also, cases were significantly more likely to be current or former smokers.)

Other differences between groups included lower rates of joint manifestations among cases, both at the first visit and at last follow-up.

What did change over time was the onset of pulmonary hypertension during follow-up. At baseline, 26% of cases and 9% of controls showed pulmonary hypertension. At last follow-up, these proportions rose by 12 percentage points in cases versus 6 points in controls. In both groups, pulmonary arterial hypertension accounted for about two-thirds of these diagnoses, followed by pulmonary hypertension related to lung diseases in one-third of diagnoses; cardiac disease-related pulmonary hypertension diagnoses were noted in a handful of patients.

Survival was significantly impaired among cases versus controls. At year 5 after patients' first UPMC visit, 68% of cases were still alive compared with 76% of controls (P=0.02). Pulmonary hypertension and interstitial lung disease were the most common causes of death related to scleroderma. However, those data were not adjusted for covariates such as smoking, and did not take account of the antibody-positive group's longer disease duration before coming to UPMC.

Domsic and colleagues called the 38% rate of pulmonary hypertension in antibody-positive patients "striking," "very high," and "of seminal importance." It also has practical implications because anti-Th/To testing is now , the group wrote.

  • author['full_name']

    John Gever was Managing Editor from 2014 to 2021; he is now a regular contributor.

Disclosures

Domsic reported relationships with Formation Biologics, Eicos Sciences, Corbus Pharmaceutical Holdings, and Boehringer Ingelheim. Other authors declared they had no relevant financial interests.

Primary Source

Arthritis & Rheumatology

Suresh S, et al "Over one-third of Th/To antibody positive scleroderma patients develop pulmonary hypertension in long-term follow-up" Arthritis Rheumatol 2022; DOI: 10.1002/art.42152.