Granzyme A

Also: GZMA

Granzymes are exogenous serine proteinases released from cytoplasmic granules of cytotoxic lymphocytes (CTLs) and NK cells. The name “granzymes” is derived from: granules + enzymes. Upon binding of the CTL to a target cell, the contents of the granules are released in the intercellular space where perforin perforates the target cell membrane by forming transmembrane pores. Through these pores, granzymes enter the cytosol of the target cell to intiate the apoptotic pathway. Not all granzymes enter the target cell as some are present in the peripheral blood and other biological fluids. Though detectable amounts of granzymes have been found to circulate in healthy volunteers, increased levels serve as biomarkers for many diseases including patients with systemic viral infections such as EBV, HIV, CMV, hepatitis A and Dengue fever. Additionally, lymphomas and carcinomas show a high percentage of Granzyme B positive CTLs in glands of patients suffering from Hodgkin’s disease which correlates with a poor prognosis. In rheumatoid arthritis, soluble Granzyme A and B levels are increased in synovial fluid; significantly higher than levels in patients with osteoarthritis. In transplantation, Granzymes are likely involved in the acute rejection of kidney-transplants, as infiltrating lymphocytes in the rejected kidney strongly express granzymes.