Diagnostic assays for myeloperoxidase deficiency

Polymorphonuclear neutrophils (PMN) represent the dominant cell in the acute response to microbial infection. Effective antimicrobial activity reflects the combined action of soluble agents in plasma with PMN-derived reactive oxygen species and granule proteins, including the azurophilic granule protein myeloperoxidase (MPO). The inhibition or absence of the MPO-H2O2-halide system results in marked reduction in PMN killing of a variety of microbes, implicating its relative prominence in the hierarchy of PMN antimicrobial systems. Although the most profound clinical defects are manifested in patients lacking the capacity to generate reactive oxygen species, as seen in chronic granulomatous disease, an inherited deficiency of MPO can also increase the frequency or severity of clinical infections. As a first step in evaluating the MPO-dependent system, determination of peroxidase activity of isolated leukocytes enriched for PMN coupled with histochemical staining of leukocytes allows assessment of functional MPO within PMN. Immunoblotting of the isolated leukocytes for MPO provides additional information, supplying insight into the molecular basis of the observed absence of functional enzyme.