Streptococcal pneumoniae Sepsis in Splenectomized Patients With Autoimmune Lymphoproliferative Syndrome (ALPS) C. J. Geaney1, J. K. Dale2, F. Dugan3, V. Rao3, T. A. Fleisher4, S. E. Straus5; 1Allergy/Immunology WR, NIAID and Immunology Service NIH, Walter Reed Army Med Center and National Institutes of Health, Washington, DC, 2National Insitute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 3National Institute of Allergy and Infectious Diseases, National Institues of Health, Bethesda, MD, 4National Institue of Allergy and Infectious Diseases, Immunology, Department of Laboratory Medicine, National Institues of Health, Bethesda, MD, 5Lab of Clinical Infectous Diseases, National Institues of Allergy and Infectous Diseases, National Institute of Health, Bethesda, MD. INTRODUCTION: Autoimmune Lymphoproliferative Syndrome (ALPS) is characterized by chronic nonmalignant lymphadenopathy, splenomegaly, increased incidence of autoimmune disease, lymphoma, and expansion of CD3+CD4-CD8-TCR cells. Many ALPS patients have undergone splenectomy for severe, refractory hypersplenism and immune cytopenias. We have been interested in determining whether their risk for post-splenectomy Streptococcal pneumoniae (S. pneumoniae) infections is similar or greater than other asplenic populations. CASE SERIES: A convenience sample of 10 ALPS patients (median age of 8.6 years; range 3.25 to 34.5 years) were selected. Of 6 patients experiencing at least one episode of sepsis post splenectomy 4 were complying with antibiotic prophylaxis and 0 had protective titers for Streptococcus pneumoniae despite vaccination on > 1 occasion(s). Of 4 patients who did not experience sepsis, 3 had nonprotective serum titers despite vaccination, 2 were antibiotic prophylaxis compliant, 1 was noncompliant with antibiotic prophylaxis, 1 was off prophylaxis since accessory spleens were documented. DISCUSSION: Since hypersplenism with cytopenias is a common feature of ALPS splenectomy is often justified. Among our cohort of 170, nearly 50% are asplenic. Splenectomized patients are at increased risk for fulminant sepsis due to S.pneumoniae. We suspect the risk of sepsis may be further complicated in ALPS patients due to an inability to sustain protective antibody titers. CONCLUSION: Asplenic ALPS patients may have a higher than expected lifetime risk for life-threatening S. pneumoniae bacteremia. A plan to protect against and manage suspected sepsis in this setting should include patient education, medic-alert identification, prophylactic antibiotics, and appropriate S. pneumoniae vaccination with periodic reassessment of serological status.
Immune Defects Associated With Dysmorphic Disorders
S. A. Mahmoud1, M. Lowery-Nordberg2, H. Chen3, T. Thurmon3, S. Ursin3, S. L. Bahna1; 1Pediatric Allergy/Immunology, Louisiana State University Health Sciences Center, Shreveport, LA, 2Pathology, LSUHSC, Shreveport, LA, 3Pediatric Genetics, LSUHSC, Shreveport, LA. RATIONALE: Patients with dysmorphic disorders seem to have frequent respiratory infections often attributed to anatomical or neurological abnormalities, but immune defects may be contributing to their susceptibility to infections. We screened subjects with dysmorphic conditions for major hematologic, B cell and T cell defects. METHODS: We studied 84 subjects with dysmorphic disorders: 29 with chromosomal disorders, 27 with single gene disorders, and 28 with unclassified dysmorphic disorders. They were evaluated by physical examination, medical history suggestive of possible immune deficiency, CBC, serum IgG, IgA, and IgM levels, and lymphocyte subsets by flow cytometry. RESULTS: Low laboratory values (< 5th percentile for age) were detected in 54.8%; being highest in the chromosomal disorder group (79.3%) followed by the single gene disorder group (55.6%) and lowest in the unclassified group (28.6%). The most common low values were in the CD19 and CD16/56 lymphocyte subpopulations followed by IgG and IgA levels. None of the subjects had neutropenia or thrombocytopenia. History of significant recurrent infections was noted in 5 subjects, all of whom had abnormal laboratory values. The most common dysmorphic syndromes associated with abnormal laboratory values were Down syndrome followed by Turner syndrome and chromosome deletions.
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
CONCLUSIONS: Patients with dysmorphic disorders, particularly those with chromosomal disorders, have a high frequency of various B cell and T cell defects that may be contributing to their susceptibility to infection. Studies are needed to further delineate the immunologic defects in that population and to investigate a possible genetic basis at the molecular level. Funding: Louisiana State University Health Sciences Center X-Linked Lymphoproliferative Disease With Growth Hormone Deficiency A. A. Alangari1, A. Abobaker1, H. Kanegane2, T. Miyawaki2; 1Pediatrics, King Saud University, Riyadh, SAUDI ARABIA, 2Pediatrics, Toyama Medical and Pharmaceutical Univer, Toyama, JAPAN. RATIONALE: Growth Hormone (GH) deficiency was reported in a few patients with X-linked agammaglobulinemia (XLA) but never in patients with X-linked lymphoproliferative disease (XLP). CASE REPORT: A 7 years old Saudi boy started to develop recurrent chest infections, otitis media, and diarrhea at 7 months of age. His parents were far relatives. He had 3 sisters and 4 brothers who were all healthy. His height and weight were below the fifth percentile for age. He had finger clubbing and small tonsils. The rest of the examination was unremarkable. His CBC showed persistent lymphocytosis of around 20,000/ml. All of his immunoglobulins were extremely low. Lymphocytes subsets analysis showed 97% CD3+ , 25% CD4+, 52% CD8+, 4%CD19+, and 1% CD16/56+ cells. GH levels afer insulin and clonidine stimulation were significantly low, indicating GH deficiency. The patient’s monocytes expression of Btk and BTK gene were normal. He later developed a left cervical lymph node enlargement. A biopsy was consistent with diffuse, large B-cell non-Hodgkin’s lymphoma. His SAP (SLAM-associated protein) expression was reduced and mutation analysis of the SH2D1A (SAP) gene showed a novel missense mutation (His8Pro), which confirms the diagnosis of XLP. CONCLUSION: This is the first reported Saudi patient with XLP. Patients with hypogammaglobulinemia and GH deficiency should be considered to have mutations not only in BTK gene but also in SH2D1A (SAP).
Disseminated Mycobacterium Avium Complex Infection in a Patient With Complete Interferon Gamma Receptor Deficiency C. M. Mosby, R. Patel, H. Aguila, G. McSherry, H. Jyonouchi; UMDNJ, Newark, NJ. RATIONALE: Host defense against mycobacteria is dependent upon the functional integrity and interaction between mononuclear phagocytes, T cells and effective granuloma formation. Recent progress revealed the importance of IFN gamma (IFN-) and IL-12 axis for granuloma forming pathogens. An increased susceptibility to atypical mycobacterium is seen in patients with defects of IFN- and IL-12 axis. CASE REPORT: A Hispanic female born to consanguineous parents presented with persistent fever and cough at 12 months of age. A CT scan demonstrated left lower lobe consolidation and prominent mediastinal lymphadenopathy and she had a positive Mantaux test (12 X 12 mm). While she was started on a four drug regimen for tuberculosis, her blood cultures and gastric aspirates grew Mycobacterium avium that disseminated to bone marrow, spleen, liver and central nervous system, in spite of aggressive combination chemotherapy. RESULTS: Conventional immune workup results were unremarkable and given her clinical presentation, defects involving IFN- and IL-12 axis were suspected. Further studies revealed elevated IFN- production by her peripheral blood mononuclear cells with PHA and Con A, but normal production with IL-12. IL-12 production with these mitogens was low but her cells produced high normal levels of IL-12 with IL-12p70 and IL18. ELISPOT revealed increase in IFN- production as well. With these findings, IFN- receptor (IFN-R) defect was suspected and complete IFN-R defect was confirmed by flow cytometry (Dr. Holland’s laboratory at NIH). CONCLUSION: This case demonstrates an importance of IFN- for eradicating atypical mycobacterium and also altered PPD reactivity to Mycobacterium avium in patients with IFN-R defect.