Adult-Onset Chronic Granulomatous Disease and CD10-Negativity in Neutrophils

On August 8, 2003, a 23-year-old male was referred to our hospital because of an abnormal shadow in the right lung. He had no family members affected with immunodeficiency disorders. He was diagnosed as having pneumonia. On August 1, 2005, he was admitted again because of pneumonia. Serum IgG, IgA, and IgM levels were normal. An antihuman immunodeficiency virus test was negative. An abdominal computed tomographic scan showed multiple lowdensity lesions in the spleen, which led to the suspicion of fungal infection. On September 30, 2005, analysis of the peripheral blood lymphocytes showed normal T-cell subsets and a normal CD4/CD8 ratio. He developed intractable skin inflammatory lesions due to methicil l in-sensit ive Staphylococcus aureus. On December 14, 2010, the patient was referred to the Division of Hematology to determine a diagnosis for the repeated infections. He had low-grade fever. Peripheral blood neutrophils were morphologically normal without abnormal cytoplasmic granules. The serum CRP level was 6.33 mg/dl. The patient’s clinical course was strongly suggestive of disorders related to neutrophil dysfunction. Phenotypes of the peripheral blood neutrophils were CD11b , CD13 , CD15 , CD33 , and phosphatidyl glucoside as well as CD10, CD14 , CD34 , CD36 , and HLA-DR (Fig. 1). These phenotypes were consistent with phenotypes of neutrophils, except for CD10. Superoxide production from neutrophils stimulated by phorbol 12-myristate 13-acetate was measured by flow cytometry using dihydrorhodamine 123 : superoxide production from the patient’s neutrophils slightly decreased compared with that from a healthy volunteer’s neutrophils (Fig. 2B). The analysis of an extracellular epitope on heme-binding membrane glycoprotein gp91phox by flow cytometry using the monoclonal antibody 7D5, which specifically binds to the epitope of the neutrophils, showed slightly decreased expression in the patient’s neutrophils (Fig. 2D). Cytochrome b subunit b (CYBB) gene analysis of the patient’s leukocytes did not show mutations (data not shown). The patient was diagnosed with chronic granulomatous disease (CGD) without CYBB gene mutation. One of the mechanisms of CGD in our patient is suggested to be decreased expression of the CYBB gene, leading to relatively mild CGD. There are two novelties in our patient : one is the adult onset of CGD and the other is CD10-negativity in neutrophils. According to the Primary Immunodeficiency Database in Japan, adult onset of CGD occurred in only 1.1% of cases (2 out of 187 patients). There are several reports on the late onset of CGD. Recurrent and intractable bacterial or fungal infections led to the suspicion of CGD in these patients. Although CGD usually occurs in children, this disorder should be considered for adults with recurrent and intractable infections. CD10, a neutral endopeptidase, is expressed on lymphocyte precursors, a subset of B cells and neutrophils under normal conditions. CD10 hydrolyzes biologically active peptides, leading to neutrophil inflammatory responses via the migration and aggregation of cells. In severe infections such as those in burn and sepsis, CD10 expression on neutrophils decreases transiently, suggesting either active bone marrow release of the cells or a response to inflammatory challenge to the cells, or both. An injection of lipopolysaccharide from Escherichia coli to healthy volunteers causes reduced CD10 expression on neutrophils with