Search

Background and Case Presentation: We report a case of septic shock syndrome caused by Streptococcus pneumoniae in a patient who had undergone splenectomy due to an autoimmune lymphoproliferative syndrome (ALPS), which is characterized as a dysfunction of immunoregulation. Although the patient was vaccinated with a conjugated polysaccharide vaccine after the splenectomy, he was still susceptible to S. pneumoniae infection, because the isolated serovar (24F), a serovar long thought to be apathogenic, is not covered by any vaccine currently approved, neither a conjugated nor an unconjugated polysaccharide one., Conclusions: This case demonstrates that, due to presence of different serovars, also infections with bacteria against which patients are vaccinated have to be considered as differential diagnosis. Although vaccine development has extended the coverage of S. pneumoniae from 7 to 23 serovars within recent years, there is still demand for novel vaccines which can provide broader protection also against so-thought "apathogenic" strains, especially for groups at high risk.

Autoimmune lymphoproliferative syndrome (ALPS) caused by impaired FAS-mediated apoptosis of lymphocytes is characterized by lymphoproliferation, autoimmunity, but also an increased risk of invasive bacterial infection, notably following splenectomy. We surveyed a cohort of 100 ALPS patients (including 33 splenectomized) and found that 12 (10 splenectomized) had experienced 23 invasive bacterial infections mainly caused by Streptococcus pneumoniae. This vulnerability was associated with evidence of defective B-cell function characterized by low serum immunoglobulin (Ig) M, low IgM antibody production in response to S pneumoniae following nonconjugated immunization, and low blood memory B-cells counts (including marginal zone [MZ] B-cell counts). This immunodeficiency strongly correlated with intensity of lymphoproliferation. Spleen sections from 9 ALPS patients revealed double-negative T-cell (DN-T) infiltration of the MZ, which was depleted of B cells. MZ in ALPS patients contained an abnormally thick layer of MAdCAM-1((+)) stromal cells and an excess of DN-Ts. DN-Ts were shown to express MAdCAM-1 ligand, the α4β7 integrin. These observations suggest that accumulating DN-Ts are trapped within stromal cell meshwork and interfere with correct localization of MZ B cells. Similar observations were made in spleens of fas-deficient mice. Our data revealed an unexpected mechanism by which ALPS results in anti-polysaccharide IgM antibody production-specific defect. Splenectomy should be avoided., (© 2014 by The American Society of Hematology.)

Autoimmune lymphoproliferative syndrome (ALPS) is an uncommon disorder of Fas-mediated apoptosis that results in impaired lymphocyte death and, therefore, disturbed immune homeostasis. Besides presentation with lymphadenopathy and splenomegaly, patients with ALPS have a high incidence of autoimmune phenomena. To our knowledge, this is the first description of polyarteritis nodosa that includes numerous arterial aneurysms in a child with ALPS. Active vasculitis resolved after allogeneic hematopoietic stem cell transplantation. This report of polyarteritis nodosa associated with human ALPS supports previous findings in Fas-deficient mouse models that frequently develop vasculitic manifestations and suggests that apoptotic defects of lymphocytes may play a role in the pathophysiology of systemic vasculitis. Thus, patients with ALPS might be more susceptible to autoimmune vessel inflammation. This case furthermore emphasizes that even rare autoimmune manifestations should be considered and investigated in patients with immunodeficiencies, because that might help in planning treatment strategies for these patients.