Daniel M. Musher, M.D.

Molecular and Human Genetics

Studies of pneumococcus

Dr. Musher’s research asks why some persons develop pneumonia due to Streptococcus pneumoniae (Spn), the most common and potentially serious form of that disease, why others do not, and what might stimulate a protective humoral immune response. His initial studies examined the radioimmunoassay that measured anti-capsular antibody, documented its nonspecificity and developed a specific ELISA to measure IgG to capsular polysaccharide (CPS) of Spn. Dr. Musher found IgG to each CPS in about 30% of healthy adults and showed that autosomal codominant inheritance governed the inability of some persons to make such IgG. In others, especially if elderly or diseased, IgG detected by ELISA may be poorly functional. Serum from two-thirds of patients admitted to VAMC for pneumococcal pneumonia lacked IgG to the infecting serotype; 14 had received pneumococcal vaccine. In one-third of patients, IgG was present but did not opsonize the infecting pneumococcal serotype for phagocytosis in vitro or protect mice against experimental infection. These results elucidate the incomplete protection by pneumococcal vaccine. Persons who can not respond or who make poorly functional IgG may not be protected, but it is not known how to predict such responses, and continued use of vaccine is recommended. IgG to other surface constituents of Spn may protect persons with poor responses to CPS who remain free of disease.

Dr. Musher’s nomination was based on the following publications:

Musher DM, Groover JE, Watson DA, Pandey JP, Rodriguez-Barradas MC, Baughn RE, Pollack MS, Graviss EA, de Andrade M, Amos CI." Genetic regulation of the capacity to make immunoglobulin G to pneumococcal capsular polysaccharides. ". J Investig Med. 1997 Feb;45(2):57-68.

Rodriguez-Barradas MC, Tharapel RA, Groover JE, Giron KP, Lacke CE, Houston ED, Hamill RJ, Steinhoff MC, Musher DM. " Colonization by Streptococcus pneumoniae among human immunodeficiency virus-infected adults: prevalence of antibiotic resistance, impact of immunization, and characterization by polymerase chain reaction with BOX primers of isolates from persistent S. pneumoniae carriers. ". J Infect Dis. 1997 Mar;175(3):590-7.

Musher DM, Groover JE, Reichler MR, Riedo FX, Schwartz B, Watson DA, Baughn RE, Breiman RF. " Emergence of antibody to capsular polysaccharides of Streptococcus pneumoniae during outbreaks of pneumonia: association with nasopharyngeal colonization. ".Clin Infect Dis. 1997 Mar;24(3):441-6.

Musher DM, Groover JE, Watson DA, Rodriguez-Barradas MC, Baughn RE. " . IgG responses to protein-conjugated pneumococcal capsular polysaccharides in persons who are genetically incapable of responding to unconjugated polysaccharides. ". Clin Infect Dis. 1998 Dec;27(6):1487-90.