Israel Medical Association Journal

Thrombosis is a common phenomenon in patients with malignancies. It is believed that thrombosis is multifactorial and that in addition to mechanisms directly associated with cancer and its treatment, it may also be related to the interaction between the immune system and clotting. The present work describes four cancer patients (three adults and one child) whose clinical course was characteristic of catastrophic antiphospholipid syndrome (CAPS) in intensive care units of the National Cancer Institute of Rio de Janeiro. The presence of findings similar to those in CAPS can be attributed to an unbalanced interaction between the immune system and coagulation.

The major autoantigens in the inflamed synovium in rheumatoid arthritis (RA) are citrullinated peptides. Citrullinated peptides are employed in diagnostic kits for detection of anti-citrullinated protein antibodies (ACPA), a serological marker with high specificity and sensitivity in the diagnosis of RA, and have been included in the new ACR/EULAR classification criteria for RA. ACPA-positive RA patients suffer from an erosive and more aggressive disease compared to ACPA-negative patients. In view of the mounting indications that ACPA plays a seminal role in the pathogenesis of RA, it might be valuable to pursue a specific treatment aiming ACPA as a target. We found that citrullinated peptides, which contain a unique amino acid, citrulline, alter the protein structure within the connective tissue, leading to tolerance breakdown and triggering the autoimmune response in RA. However, with different doses and routes of administration, citrullinated peptides can promote immune tolerance rather than induction of disease. 

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of the innate and adaptive immune systems with the production of autoantibodies by stimulated B lymphocytes. The BLyS protein (B lymphocyte stimulator) is secreted mainly by monocytes and activated T cells and is responsible for the proliferation, maturation and survival of B cells.

Objectivs: To study sera BLyS level and its clinical significance in Israeli lupus patients over time.

Methods: The study population included 41 lupus patients (8 males, 33 females; mean age 35.56 ± 15.35 years) and 50 healthy controls. The patients were followed for 5.02 ± 1.95 years. We tested 221 lupus sera (mean 5.4 samples/patient) and 50 normal sera for BLyS levels by a capture ELISA. Disease activity was determined by the SLEDAI score.

Results: Sera BLyS levels were significantly higher in SLE patients than in controls (3.37 ± 3.73 vs. 0.32 ± 0.96 ng/ml, P < 0.05). BLyS levels were high in at least one sera sample in 80.5% of the patients but were normal in all sera in the control group. There was no correlation between sera BLyS and anti-ds-DNA autoantibody levels. BLyS levels fluctuated over time in sera of lupus patients with no significant correlation to disease activity.

Conclusions: Most of our lupus patients had high sera BLyS levels, suggesting a role for BLyS in the pathogenesis and course of SLE. Our results support the current novel approach of targeting BLyS (neutralization by antibodies or soluble receptors) in the treatment of active lupus patients.