Early intravenous immunoglobulin replacement in hypogammaglobulinemic heart transplant recipients: results of a clinical trial.

BACKGROUND: Immunoglobulin G (IgG) hypogammaglobulinemia (HGG) is a risk factor for development of severe infections after heart transplantation. We performed a clinical trial to preliminarily evaluate the efficacy and safety of early administration of intravenous immunoglobulin (IVIG) for prevention of severe infection in heart recipients with post-transplant IgG HGG. METHODS: Twelve heart recipients with IgG HGG detected in a screening phase of the clinical trial (IgG <500 mg/dL) were recruited. Patients received IVIG (Flebogamma 5%), as follows: 2 doses of 200 mg/kg followed by up to 5 additional doses of 300 mg/kg to maintain IgG >750 mg/dL. IgG and specific antibody titers to distinct microorganisms were tested during follow-up. The primary outcome measure was development of severe infection during the study period. Data on the primary outcome were matched with those of 13 recipients with post-transplant HGG who were not included in the clinical trial and with those of 11 recipients who did not develop HGG during the same study period. RESULTS: Mean time to detection of HGG was 15 days. IgG and specific antibody reconstitution (anti-cytomegalovirus, anti-Haemophilus influenza, and anti-hepatitis B surface antigen antibodies) was observed in IVIG-treated patients. Severe infection was detected in 3 of 12 (25%) IVIG-treated recipients, in 10 of 13 (77%) HGG non-IVIG patients, and in 2 of 11 (18%) non-HGG patients (log-rank, 15.31; P=.0005). No severe IVIG-related side effects were recorded. CONCLUSION: Data from this study demonstrate that prophylactic IVIG replacement therapy safely modulates HGG and specific antimicrobial antibodies. Our data also preliminarily suggest that IVIG replacement therapy might decrease the incidence of severe infection in heart recipients with HGG.

Coexistence of lymphocyte dysregulation, alloimmunity and autoimmunity in a patient with recurrent failed in vitro embryo transfer fertilization / Coexistencia de alteracion inmunofenotipica linfocitaria, aloinmunidad y autoinmunidad en una paciente con fallo de implantacion recurrente tras fecundacion in vitro

Objective. To describe a patient with primary infertility and recurrent implantation failure (RIF) and coexistence of peripheral blood immunophenotypic dysregulation of lymphocytes and alloimmune and autoimmune abnormalities. The hypothesis is that functionally distinct immunological abnormalities might better explain the immunological etiology of RIF than individual abnormalities in some patients. Subjects and methods. We present clinical and immunological data. Results. A patient with primary infertility and RIF had peripheral blood immunophenotypic abnormalities of T, B and NK-cells, unusually high shared HLA antigens with her partner, and antiphospholipid antibodies. Conclusion. Functionally distinct immunological abnormalities may coexist in some women with RIF after in vitro fertilization (AU)

Objetivo. Describir un caso de fallo recurrente tras fecundación in vitro en el que coexisten varias alteraciones inmunológicas potencialmente relacionadas con este problema. La hipótesis es que esta coexistencia de factores podría explicar mejor la etiología inmunológica que alteraciones individuales. Sujetos y métodos. Se presentan datos clínicos e inmunológicos. Resultados. Una paciente con infertilidad primaria y fallo recurrente tras 4 intentos de fecundacion in vitro tenía alteraciones inmunofenotípicas de células T, B y NK, antígenos compartidos por la pareja en una frecuencia inusualmente alta y anticuerpos antifosfolípidos. Conclusiones. Distintas alteraciones inmunológicas pueden coexistir en casos aislados de fallo recurrente tras fecundación in vitro (AU)

CD8+DR+ T-Cells and C3 Complement Serum Concentration as Potential Biomarkers in Thrombotic Antiphospholipid Syndrome.

Purpose. To assess complement factors and T lymphocyte activation subset abnormalities in patients with thrombotic antiphospholipid syndrome (APS) as potential biomarkers for development of clinical complications. Methods. We assessed C3, C4, factor B concentrations (nephelometry), complement haemolytic functional activity (CH100, radial immune diffusion), and the activation status of CD4+ and CD8+ T-cells (three-colour flow cytometry) in patients with thrombotic APS. Antiphospholipid (aPL) positive patients without APS-related clinical criteria, systemic lupus erythematosus (SLE) patients, and healthy individuals were evaluated as controls. A clinical followup was performed to assess the potential relationship between the immunological parameters and development of APS-related complications. Results. Lower concentrations of C3 and higher levels of CD8+DR+ cells were risk factors for development of APS-related complications during followup, including rethrombosis and neuropsychiatric symptoms. Patients with diagnosed thrombotic APS had significantly lower levels of C3, C4, and CH100 as well as higher percentages of activated CD4+DR+ and of CD8+DR+ T-cells than healthy controls but similar to that observed in autoimmune disease controls. Conclusion. Lower C3 and C4 complement levels and higher percentages of CD8+DR+ T-cells were observed in thrombotic APS patients. The potential role of these abnormalities as biomarkers of clinical outcome warrants further evaluation in a multicenter study.