Immunologic responses to bacteriophage ϕX 174 in immunodeficiency diseases

Ochs, Hans D.; Davis, Starkey D.; Wedgwood, Ralph

doi:10.1172/jci106756

Cited by 210 publications

(141 citation statements)

References 18 publications

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“…The human immune response to foreign antigens is often studied after vaccination or monitored using the bacteriophage oX174 (5). The latter antigen is potent and causes no recognized toxic effects in humans.…”

Section: Islet Cell Autoantibodiesmentioning

confidence: 99%

Autoantibodies in Diabetes

et al. 2005

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Islet cell autoantibodies are strongly associated with the development of type 1 diabetes. The appearance of autoantibodies to one or several of the autoantigens-GAD65, IA-2, or insulin-signals an autoimmune pathogenesis of ␤-cell killing. A ␤-cell attack may be best reflected by the emergence of autoantibodies dependent on the genotype risk factors, isotype, and subtype of the autoantibodies as well as their epitope specificity. It is speculated that progression to ␤-cell loss and clinical onset of type 1 diabetes is reflected in a developing pattern of epitopespecific autoantibodies. Although the appearance of autoantibodies does not follow a distinct pattern, the presence of multiple autoantibodies has the highest positive predictive value for type 1 diabetes. In the absence of reliable T-cell tests, dissection of autoantibody responses in subjects of genetic risk should prove useful in identifying triggers of islet autoimmunity by examining seroconversion and maturation of the autoantibody response that may mark time to onset of type 1 diabetes. The complexity of the disease process is exemplified by multiple clinical phenotypes, including autoimmune diabetes masquerading as type 2 diabetes in youth and adults. Autoantibodies may also provide prognostic information in clinically heterogeneous patient populations when examined longitudinally. Diabetes 54 (Suppl. 2):S52-S61, 2005

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Section: Islet Cell Autoantibodiesmentioning

confidence: 99%

Autoantibodies in Diabetes

et al. 2005

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“…35 In vivo antibody responses were evaluated using immunization with the T cell-dependent neoantigen, bacteriophage FX174, as described previously. 36,37 Surface staining and flow cytometry for functional CD40 ligand expression were performed on stimulated lymphocytes as described previously. 38 Neutrophil oxidative burst was determined by flow cytometry using dihydrorhodamine fluorescence as described.…”

Section: Prophylaxis Against Infectionmentioning

confidence: 99%

Intensive postgrafting immune suppression combined with nonmyeloablative conditioning for transplantation of HLA-identical hematopoietic cell grafts: results of a pilot study for treatment of primary immunodeficiency disorders

Burroughs

Storb

Leisenring

et al. 2007

Bone Marrow Transplant

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This study was designed to determine the safety of a nonmyeloablative regimen in patients with primary immunodeficiency disorders (PID) who had infections, organ dysfunction or other risk factors that precluded conventional hematopoietic cell (HC) transplant. Fourteen patients received HLA-matched related (n ¼ 6) or unrelated (n ¼ 8) HC grafts from marrow (n ¼ 8), peripheral blood mononuclear cells (n ¼ 5) or umbilical cord blood (n ¼ 1), either without conditioning (n ¼ 1), or after 200 cGy total body irradiation alone (n ¼ 3) or with 90 mg/m 2 fludarabine (n ¼ 10). All patients were given postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. Mixed (n ¼ 5) or full (n ¼ 8) donor chimerism was established in 13 patients, and one patient rejected the graft. Eight patients developed acute grade III (n ¼ 1) and/or extensive chronic GVHD (n ¼ 8). With a median follow-up of 4.9 (range, 0.7-8.1) years, the 3-year overall survival, event-free survival and transplant-related mortality were 62, 62 and 23%, respectively. Correction of immune dysfunction was documented in 8 of 10 patients with stable donor engraftment. These preliminary results indicated that this approach was associated with stable donor engraftment and a low incidence of early mortality and, thus, can be considered for certain high-risk patients with PID. However, there was a risk of GVHD, which is an undesirable outcome for this group of patients.

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“…Using X174, it was demonstrated that patients who are immunocompromised appear less likely to mount a response to bacteriophage administration. 19 A study performed in Poland confirms this observation. 20 From the clinical viewpoint, most septic patients are immunologically compromised.…”

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confidence: 65%

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Gene Ther

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Immunologic responses to bacteriophage ϕX 174 in immunodeficiency diseases

Cited by 210 publications

References 18 publications

Autoantibodies in Diabetes

Autoantibodies in Diabetes

Intensive postgrafting immune suppression combined with nonmyeloablative conditioning for transplantation of HLA-identical hematopoietic cell grafts: results of a pilot study for treatment of primary immunodeficiency disorders

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