Immune function in patients with Shwachman-Diamond syndrome

Shwachman-Diamond syndrome (SDS) is an inherited multisystem disorder chara cterized by exocrine pancreatic dysfunction and varying degrees of cytopeni a. In addition, various immunological abnormalities have been noted. To cla rify the issue of immunological competence or incompetence in SDS, we prosp ectively studied immune function in 11 patients with SDS. Seven suffered fr om recurrent bacterial infections and six from recurrent viral infections. Varying degrees of impairment were readily identified. All patients had neu tropenia; total lymphocyte counts, however, were normal in all except one p atient. Nine patients had B-cell defects comprising one or more of the foll owing abnormalities: low IgG or IgG subclasses, low percentage of circulati ng B lymphocytes, decreased in vitro B-lymphocyte proliferation and a lack of specific antibody production. Seven out of nine patients studied had at least one T-cell abnormality comprising a low percentage of total circulati ng T lymphocytes or CD3(+)/CD4(+) cell subpopulations or decreased in vitro T-lymphocyte proliferation. Five out of six patients studied had decreased percentages of circulating natural killer cells. Moreover, neutrophil chem otaxis was significantly low in all the patients studied. These data point to a major immunodeficiency component in SDS that places patients at height ened risk of infections, even if neutrophil numbers are protective. This fi nding broadens the definition of the syndrome substantially: it suggests th at the SDS marrow defect occurs at the level of an early haematological-lym phocytic stem cell or that a combined marrow and thymic stromal defect acco unts for the aberrant function of haematopoietic and lymphopoietic lineages .