Background/Purpose:

Macrophages are the primary inflammatory cell type present in the systemic sclerosis (SSc) skin. Circulating monocytes can give rise to profibrotic inflammatory cells such as alternatively activated macrophages in the fibrotic end-organ such as skin and lung. Despite their importance, there are no previous studies examining the clinical correlates of peripheral blood monocyte count in SSc. The primary objective of the present study was to examine the association of monocyte count with clinical variables and survival in the prospective Genetics Versus Environment In Scleroderma Outcome Study (GENISOS) cohort.

Methods:

Monocyte count was prospectively obtained at enrollment in 429 patients. All patients had disease duration less than 5 years (from the first non-Raynaud’s phenomenon symptom) and fulfilled the 2013 ACR/EULAR criteria. Modified Rodnan Skin Score (mRSS) and forced vital capacity % predicted (FVC%) were also obtained prospectively. SSc related autoantibodies were determined in the divisional laboratory using gold standard methods. After mean follow-up of 8.3 years, 129 patients had died.

Results:

The mean disease duration at enrollment was 2.4 years and the majority of patients had diffuse cutaneous involvement (60.4%). Higher monocyte count was associated with diffuse cutaneous disease type (b=59.4, p=0.012). Furthermore, higher monocyte count was significantly associated with higher baseline mRSS (r=0.17, p=0.001) while there was no correlation with baseline FVC%. There was a trend for association of higher monocyte counts with RNA polymerase III positivity (b=55.2, p=0.055) while there was no association with other SSc-related autoantibodies. Higher monocyte count also correlated with lower disease duration at the baseline visit (r=-0.11, p=0.022)

In the multivariable cox regression analysis after adjustment for age at enrollment, monocyte count was associated with higher mortality (p=0.028). Next, patients were classified based on normal vs. high monocyte count as reported by the clinical laboratory. SSc patients with a high monocyte count had higher mortality even after adjustment for age and baseline mRSS (see Table).

Conclusion:

Higher peripheral blood monocyte count was associated with shorter disease duration, more extensive skin disease, and higher mortality. This study provides clinical support for relevance of monocytes and bone marrow derived macrophages in SSc pathogenesis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/higher-baseline-monocyte-count-is-associated-with-more-extensive-skin-involvement-and-higher-mortality-in-systemic-sclerosis/