Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: A multicenter prospective study.

BACKGROUND: New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections. METHODS: We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection. RESULTS: During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection. CONCLUSION: Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection.

[Mixed cryoglobulinemia and related immunological disorders after hepatic transplantation for hepatitis C cirrhosis. Case report]. / Crioglobulinemia mixta y otras alteraciones inmunologicas en trasplante hepatico por cirrosis por virus de la hepatitis C. Reporte de un caso.

Cryoglobulinemia may be found in up to 30% of patients that had received liver transplants after hepatitis C virus (HCV) cirrhosis. Three types of cryoglobulinemia are recognized: type I, composed of monoclonal immunoglobulins associated with lymphoproliferative diseases and myeloma; type II cryoglobulinemia are comprised of a monoclonal component which has rheumatoid factor activity and hence binds to polyclonal immunoglobulins (in certain parts of the world have been found to be associated with hepatitis C infection); and type III cryoglobulinemia consist exclusively of polyclonal immunoglobulins with rheumatoid factor activity (associated with connective tissue diseases and chronic infections including hepatitis C). Immunocompetence, autoimmunity and clonal expansion of B cell lymphocytes have not been analysed simultaneously in previous reports of patients with cryoglobulinemia after liver transplantation. We here describe immunological abnormalities associated with cryoglobulinemia in a patient who had received liver transplant for HCV cirrhosis. In addition, in the present work HCV RNA determination was performed directly in the cryocrit and not only in peripheral blood. We have observed enrichment of HCV RNA in the cryoprecipitates which might be a better demonstration of the possible role of HCV in the pathogenesis of the cryoglobulinemia.

[Antiphospholipid antibodies evolving into connective tissue disease: follow-up study of women with recurrent misscarriage]. / Anticuerpos antifosfolipídicos y evolución a conectivopatía: estudio de seguimiento de mujeres con abortos recurrentes.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the clinical and immunologic profile, the rate of progression to connective tissue disease and the possible predictors of evolution in patients with antiphospholipid antibodies and abortions. PATIENTS AND METHOD: In a prospective follow-up study, we determined the prevalence of antiphospholipid antibodies as well as other autoimmune abnormalities and the evolution to connective tissue disease in 200 women with unexplained recurrent abortions. IgG and IgM anticardiolipin antibodies were determined by ELISA and the lupus anticoagulant was determined by means of coagulometric tests. RESULTS: Of 200 women with pregnancy losses, 69 (34.5%) had antiphospholipid antibodies. Thirty-one of 200 women (15.5%) had high or moderate positive anticardiolipin antibodies. During a mean follow-up of 32 months, 9 (13%) antiphospholipid-antibody-positive patients developed features of lupus- like disease or systemic lupus erythematosus. A low total hemolytic complement, increased circulating immune complexes and positive antinuclear antibodies (ANA) were more common in those patients evolving to a connective tissue disorder (p < 0.001, p = 0.003 and p < 0.001, respectively). Positive ANA in women with antiphospholipid antibodies predicted independently the evolution to a connective tissue disorder [Cox proportional hazard model; relative hazard = 4.92, p = 0.04]. CONCLUSIONS: A subgroup of patients with antiphospholipid antibodies and abortions may progress to a connective tissue disorder. A positive antinuclear antibody test result could be useful to identify those patients with antiphospholipid antibodies and abortions who are prone to evolve into a systemic autoimmune disease.

Anticuerpos antifosfolipídicos y evolución a conectivopatía: estudio de seguimiento de mujeres con abortos recurrentes / Antiphospholipid antibodies evolving into connective tissue disease: follow-up study of women with recurrent misscarriage

FUNDAMENTO Y OBJETIVO: El objetivo de este estudio fue la determinación del perfil clínico e inmunológico, la tasa de progresión a conectivopatía y posibles variables predictoras de evolución en pacientes con abortos y anticuerpos antifosfolipídicos. PACIENTES Y MÉTODO: Estudiamos prospectivamente la prevalencia de anticuerpos antifosfolipídicos, otras alteraciones autoinmunitarias y su evolución a conectivopatía en 200 mujeres con aborto recurrente. Los anticuerpos antifosfolipídicos se determinaron mediante técnica de enzimoinmunoanálisis (anticuerpos anticardiolipina IgG e IgM) y por técnicas coagulométricas (anticoagulante lúpico). RESULTADOS: De 200 mujeres con abortos, 69 (34,5 per cent) tuvieron anticuerpos antifosfolipídicos. Treinta y un pacientes (15,5 per cent) tenían anticuerpos anticardiolipina a título moderado-alto. Tras una media de seguimiento de 32 meses, 9 pacientes con anticuerpos antifosfolipídicos (13 per cent) evolucionaron a lupus eritematoso sistémico o a enfermedad lupus like. Se observaron con más frecuencia cifras bajas de complemento hemolítico total, concentraciones elevadas de inmunocomplejos circulantes y anticuerpos antinucleares positivos en las pacientes con anticuerpos antifosfolipídicos que evolucionaron a conectivopatía frente a las que no lo hicieron (p < 0,001, p = 0,003 y p < 0,001, respectivamente). La positividad de anticuerpos antinucleares en las pacientes con anticuerpos antifosfolipídicos predijo de forma independiente la evolución a conectivopatía mediante análisis de regresión de Cox (riesgo relativo = 4,92; p = 0,04).CONCLUSIONES: Un subgrupo de pacientes con abortos y anticuerpos antifosfolipídicos puede evolucionar a conectivopatía. La positividad de los anticuerpos antinucleares podría utilizarse para identificar a pacientes con abortos y anticuerpos antifosfolipídicos positivos que a lo largo de su evolución pueden presentar síntomas indicativos de evolución a conectivopatía sistémica (AU)