Granulocyte Transfusions in Patients with Chronic Granulomatous Disease Undergoing Hematopoietic Cell Transplantation or Gene Therapy

Journal of Clinical Immunology - Granulocyte transfusions are sometimes used as adjunctive therapy for the treatment of infection in patients with chronic granulomatous disease (CGD). However,...     

Diabetes, Renal and Cardiovascular Disease in p47 phox−/− Chronic Granulomatous Disease

Chronic granulomatous disease is a rare immunodeficiency due to defects in the phagocyte NADPH oxidase. The X-linked form (gp91 ^phox deficiency) accounts for about 70 % of cases; autosomal recessive p47 ^phox deficiency accounts for about 25 % of cases. We identified a 10 % incidence of diabetes in p47 ^phox deficient CGD, but none in X-linked CGD. Renal and cardiovascular diseases were also higher in p47 ^phox deficiency. p47 ^phox deficient CGD has non-infectious morbidities distinct from those in X-linked CGD.     

Sporothrix schenckii Lymphadentitis in a Male with X-linked Chronic Granulomatous Disease

Sporothrix schenckii lymphadenitis was identified in a 33 month old male with X-linked chronic granulomatous disease (CGD). S. schenckii is a dimorphic catalase producing fungus found in the soil of temperate and tropical climates. Host defense against S. schenckii relies primarily on innate and cellular responses and gp91^phox?/? mice are susceptible to disseminated infection. This case represents the first report of susceptibility to sporotrichosis in a patient with CGD.     

Psychrobacter immobilis Septicemia in a Boy with X-linked Chronic Granulomatous Disease and Fulminant Hepatic Failure

A 16-year old boy with chronic granulomatous disease (CGD) developed Psychrobacter immobilis septicemia during a course of fulminant hepatic failure. The patient died despite aggressive management with antimicrobials and corticosteroids. While Psychrobacter immobilis rarely affects humans, it should be considered an organism that can cause sepsis in patients with CGD.     

Proton and cation transport activity of the M2 proton channel from influenza A virus

The M2 protein is a small, single-span transmembrane (TM) protein from the influenza A virus. This virus enters cells via endosomes; as the endosomes mature and become more acidic M2 facilitates proton transport into the viral interior, thereby disrupting matrix protein/RNA interactions required for infectivity. A mystery has been how protons can accumulate in the viral interior without developing a large electrical potential that impedes further inward proton translocation. Progress in addressing this question has been limited by the availability of robust methods of unidirectional insertion of the protein into virus-like vesicles. Using an optimized procedure for reconstitution, we show that M2 has antiporter-like activity, facilitating K⁺ or Na⁺ efflux when protons flow down a concentration gradient into the vesicles. Cation efflux is very small except under conditions mimicking those encountered by the endosomally entrapped virus, in which protons are flowing through the channel. This proton/cation exchange function is consistent with the known high proton selectivity of the channel. Thus, M2 acts as a proton uniporter that occasionally allows K⁺ to flow to maintain electrical neutrality. Remarkably, as the pH inside M2-containing vesicles (pH_in) decreases, the proton channel activity of M2 is inhibited, but its cation transport activity is activated. This reciprocal inhibition of proton flux and activation of cation flux with decreasing pH_in first allows accumulation of protons in the early stages of acidification, then trapping of protons within the virus when low pH_in is achieved.     

Correlation of the MMPI with lumbosacral spine fusion results. Prospective study

This study was done to determine whether the Minnesota Multiphasic Personality Inventory (MMPI) aided in selection of appropriate lumbosacral fusion candidates, compared with those selected without an MMPI. Postoperative end-result ratings were done, categorizing patients into two groups: one group of 62 patients with a preoperative MMPI and a second group of 23 patients with no preoperative MMPI. Thirty patients with normal MMPIs, strong objective indications for initial surgery, and absence of compensation and/or litigation factors had 88% good or excellent end-results. Twenty-three patients had surgery without MMPI evaluation. Of 21 available for follow-up, 86% had good or excellent end-results. "Warning" physical signs aided selection of appropriate surgical candidates in the patients who did not have an MMPI.     

Ruxolitinib partially reverses functional natural killer cell deficiency in patients with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations

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Corticosteroid therapy for liver abscess in chronic granulomatous disease

Liver abscesses in chronic granulomatous disease (CGD) are typically difficult to treat and often require surgery. We describe 9 X-linked CGD patients with staphylococcal liver abscesses refractory to conventional therapy successfully treated with corticosteroids and antibiotics. Corticosteroids may have a role in treatment of Staphylococcus aureus liver abscesses in CGD.