Association of immunological cell profiles with specific clinical phenotypes of scleroderma disease

Abstract

This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4(+) and CD8(+) T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies.

Figure 1

Characterization of cellular subpopulations analyzed by flow cytometry. FL1: Annexin-V⁺ cells; FL2: CD3⁺ or/and CD56⁺ cells; FL3: CD4⁺ cells; FL4: CD19⁺ or CD8⁺ cells; FL5: CD25⁺ cells; SSC: side-scatter detector.

Figure 2

Box-plot of B lymphocytes.*Statistically significant relative to controls. ^‡Statistically significant relative to patients without pulmonary hypertension.

Figure 3

Box-plot of overall apoptosis regarding scleroderma type and presence of PH and PF. *Statistically significant relative to controls. ^†Statistically significant relative to patients without pulmonary hypertension.

Figure 4

Box-plot of activated NK cells. *Statistically significant relative to controls.