Immunogenicity and side-effects of the inactivated hepatitis A vaccine in periodic fever, aphthous stomatitis, pharyngitis, and adenitis patients.

The aim of this study was to compare the immunogenicity and side-effects of hepatitis A virus (HAV) vaccination between periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) patients and healthy controls who have not been previously exposed to HAV. A prospective observational study was carried out of 28 PFAPA patients and 76 controls who received two doses of the vaccine. Immunogenicity was expressed as seroconversion and seroprotection rates; mean HAV-immunoglobulin G concentration was measured at 0, 1, 7 and 18 months. Side-effects were defined as incidence of adverse events and the effect of vaccination on PFAPA symptoms. All participants were seronegative and seroconverted at 1 month. One month after primary vaccination, 92.9% of PFAPA patients and 77.6% of the controls attained seroprotection, while the rates increased to 100% and 96.1%, respectively, 1 month after the second dose. Seroprotection rates remained adequate 1 year after completion of vaccination. In conclusion, two doses of the inactivated HAV vaccine are well-tolerated and effective in children with PFAPA.

Recurrence of type 1 diabetes after simultaneous pancreas-kidney transplantation, despite immunosuppression, is associated with autoantibodies and pathogenic autoreactive CD4 T-cells.

OBJECTIVE: To investigate if recurrent autoimmunity explained hyperglycemia and C-peptide loss in three immunosuppressed simultaneous pancreas-kidney (SPK) transplant recipients. RESEARCH DESIGN AND METHODS: We monitored autoantibodies and autoreactive T-cells (using tetramers) and performed biopsy. The function of autoreactive T-cells was studied with in vitro and in vivo assays. RESULTS: Autoantibodies were present pretransplant and persisted on follow-up in one patient. They appeared years after transplantation but before the development of hyperglycemia in the remaining patients. Pancreas transplant biopsies were taken within approximately 1 year from hyperglycemia recurrence and revealed beta-cell loss and insulitis. We studied autoreactive T-cells from the time of biopsy and repeatedly demonstrated their presence on further follow-up, together with autoantibodies. Treatment with T-cell-directed therapies (thymoglobulin and daclizumab, all patients), alone or with the addition of B-cell-directed therapy (rituximab, two patients), nonspecifically depleted T-cells and was associated with C-peptide secretion for >1 year. Autoreactive T-cells with the same autoantigen specificity and conserved T-cell receptor later reappeared with further C-peptide loss over the next 2 years. Purified autoreactive CD4 T-cells from two patients were cotransplanted with HLA-mismatched human islets into immunodeficient mice. Grafts showed beta-cell loss in mice receiving autoreactive T-cells but not control T-cells. CONCLUSIONS: We demonstrate the cardinal features of recurrent autoimmunity in three such patients, including the reappearance of CD4 T-cells capable of mediating beta-cell destruction. Markers of autoimmunity can help diagnose this underappreciated cause of graft loss. Immune monitoring during therapy showed that autoimmunity was not resolved by the immunosuppressive agents used.

Retrospective assessment of islet cell autoantibodies in pancreas organ donors.

OBJECTIVE: Of deceased pancreas donors, 3-4% may have autoantibodies (AAb) to pancreatic islet cell antigens; these autoantibodies are well-established markers of type 1 diabetes. We investigated whether donor AAb positivity could affect the outcome of pancreas transplantation. RESEARCH DESIGN AND METHODS: We retrospectively tested AAb in 135 donors whose pancreata and kidneys were transplanted in type 1 diabetes patients. We measured AAb to glutamic acid decarboxylase (GAD-AAb), the tyrosine-phosphatase-like protein IA2 (IA2-AAb), and insulin (insulin-AAb). We then evaluated pancreas transplant outcome data. RESULTS: Four of 135 (2.96%) donors were AAb positive: three donors had GAD-AAb, and one donor had insulin-AAb. Their respective recipients became insulin independent on follow-up. Three of the four recipients had normal, insulin-producing grafts 3-5.8 years after transplant. The recipient of the insulin-AAb-positive donor pancreas developed chronic rejection following discontinuation of immunosuppression 3.3 years after transplant. CONCLUSIONS: Single AAb positivity did not affect the outcome of pancreas transplantation in our study.

Rarity of bacterial and viral meningitis in areas of Western Greece with fewer than 2,000 inhabitants.

The purpose of the present study was to compare the incidence of childhood meningitis in regions with fewer than 2,000 inhabitants (rural regions) and regions with more than 2,000 inhabitants (urban regions) in the prefecture of Achaia in Western Greece during 1991-2005. Included were all 555 children hospitalized for meningitis. The criteria for bacterial meningitis were (i) positive blood/cerebralspinal fluid (CSF) culture, Gram stain, or latex agglutination and/or (ii) increased beta-glucuronidase in CSF. In case of suspected bacterial meningitis, the following findings were considered: compatible clinical and laboratory findings, and whether or not a cure was achieved with antibiotic treatment and finally resulted in negative cultures. In cases of suspected viral meningitis, compatible clinical and laboratory findings were considered, together with observation of a cure without antibiotic treatment. Only 28 of 555 meningitis patients were from rural regions. The incidence per 10,000 children in rural and urban regions, respectively, was as follows: meningitis, 1.13 and 8.99; bacterial meningitis, 0.16 and 2.40; suspected bacterial meningitis, 0.52 and 3.00; and viral meningitis, 0.44 and 3.58. The incidence ratio for bacterial, suspected bacterial, and viral meningitis in urban versus rural regions was 14.85, 5.72, and 8.10, respectively. Only 2 of the 79 cases with a confirmed causative pathogen came from rural regions. In conclusion, compared to those living in urban regions, children living in rural regions are relatively spared from bacterial and viral meningitis.

A nine year old girl with thyrotoxicosis, ataxia, and chorea.

Neurologic manifestations are common in patients with thyroid disease. We describe the case of a nine year old girl with Graves disease and the unique combination of chorea and ataxia that both resolved after treatment of hyperthyroidism.