Beyond neutropenia: Immunological evaluation of patients with Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure syndrome characterized by neutropenia and pancreatic insufficiency. The current understanding of immune function in SDS is limited. We performed a retrospective study of the US-based Shwachman-Diamond Syndrome Registry (SDSR) to characterize the immunological profile of patients with SDS. Data were obtained from chart review of patients with biallelic mutations in SBDS enrolled on the SDSR (n = 223) or followed clinically at participating institutions with local IRB approval (n = 6). Immunological data were available from 409 time points on 98 individuals with SDS at healthy time points. We identified limited immune deficits, largely quantitative changes in the B-cell compartment in a subset of patients with SDS including low absolute B cells in 31% of patients and low IgM in 30% of patients. Patients with SDS with low B cells may be at increased risk for sinopulmonary, skin or soft tissue infections particularly if they also have low IgG levels. These data support a baseline immunological evaluation, including a full blood count, lymphocyte subpopulations and immunoglobulin levels, for patients with SDS. However, it is reasonable to reserve more detailed assessments for patients with recurrent or severe infections.