Oral Contraceptive Pill Use is Associated with Lower Levels of Plasma Calprotectin in Premenopausal Women.

Introduction: Neutrophil extracellular traps (NETs) are increasingly recognized as having important roles in autoimmune disease pathogenesis. In many autoimmune diseases, e.g. rheumatoid arthritis (RA) and lupus (SLE), premenopausal women have increased incidence. Understanding immunologic effects of exposures common in premenopausal women, such as oral contraceptive pill (OCP) use, is important to understanding autoimmune disease risk in women. We investigated the relationship between OCP use and circulating calprotectin, a NETosis marker relevant to autoimmune disease pathogenesis. Methods: 164 samples from healthy premenopausal women (65 current OCP users; 99 never/prior users) and 124 samples from premenopausal women at-risk for RA by family history (57 current OCP users; 67 never/prior users) were tested for plasma calprotectin levels by ELISA. Levels were compared between current and never/prior users via Welch's T-test. Results: Healthy women currently taking OCPs had lower plasma calprotectin levels than never/prior OCP users in both the derivation (0.99 μg/mL vs 1.38 μg/mL, p = 0.016) and validation (0.9 μg/mL vs 1.4 μg/mL, p = 0.001) cohorts. Similarly, in women at-risk for RA, current OCP users had lower plasma calprotectin level compared to never/prior users (1.19 μg/mL vs 1.74, p = 0.017). Discussion: Current OCP use is associated with significantly lower plasma calprotectin in healthy premenopausal women and premenopausal women at-risk for RA. Given calprotectin is considered a NETosis marker and NETosis is associated with pathogenesis in several autoimmune diseases, our findings suggest a reduction in NETosis via OCP use could be a potential mechanism influencing autoimmune disease in premenopausal women.