Tyson B Rogers | PubMed Health

PubMed2006

Urinary beta2-microglobulin is associated with acute renal allograft rejection.

BACKGROUND: Identifying urinary biomarkers associated with acute rejection (AR) of kidney allografts could improve recipient care by allowing AR to be diagnosed noninvasively and treated earlier. We attempted to identify novel biomarkers associated with AR by analyzing urinary proteins by using matrix-associated laser desorption ionization time-of-flight mass spectroscopy (MALDI-TOF MS). METHODS: Using MALDI-TOF MS, we analyzed urine samples from 30 renal allograft recipients with biopsy-proven AR, 15 allograft recipients without AR, preoperative samples from 29 kidney donors, and 10 subjects with proteinuric native kidney disease. RESULTS: In samples obtained at the time of AR, we identified a protein peak at 11.7 kd that correlated strongly with AR. In regard to its predictive power for AR, this protein peak showed sensitivity of 83.3%, specificity of 80%, positive predictive value of 89%, and negative predictive value of 70.6%, suggesting that this protein is highly associated with AR. We identified this peak as being beta2-microglobulin. This was validated by using enzyme-linked immunosorbent assay, which documented the presence of high urinary beta2-microglobulin levels in subjects with AR. CONCLUSION: Beta2-microglobulin could be a strong biomarker for AR if used in conjunction with other biomarkers, producing an AR-specific urinary protein signature. This possibility must be confirmed in a larger cohort of kidney transplant recipients.

Acute Disease↗

PubMed2005

Immunoglobulin M-to-immunoglobulin G anti-human leukocyte antigen class II antibody switching in cardiac transplant recipients is associated with an increased risk of cellular rejection and coronary artery disease.

BACKGROUND: Activation of T cells induces immunoglobulin (Ig)M-to-IgG B-cell isotype switching via costimulatory regulatory pathways. Because rejection of transplanted organs is preceded by alloantigen-dependent T-cell activation, we investigated whether B-cell isotype switching could predict acute cellular rejection and the subsequent development of transplantation-related coronary artery disease (TCAD) in cardiac transplant recipients. METHODS AND RESULTS: Among 267 nonsensitized heart transplant recipients, switching from IgM to IgG anti-human leukocyte antigens (HLA) antibodies directed against class II but not against class I antigens was associated with a shorter duration to high-grade rejection, defined as International Society for Heart and Lung Transplantation grade 3A or higher (P<0.001), a higher cumulative rejection frequency (P=0.002), accelerated development of TCAD (P=0.04), and decreased late survival (P=0.03). Conversely, the persistence of IgM anti-HLA antibodies against class II but not against class I antigens for >30 days and the lack of IgG isotype switching were associated with protection against both acute rejection (P=0.02) and TCAD (P=0.05). Alloisotype switching coincided with T-cell activation, as evidenced by increased serum levels of soluble CD40 ligand costimulatory molecules. Finally, a case-control study showed that reduction of cardiac allograft rejection by mycophenolic acid was accompanied by reduced CD40 ligand serum levels and the prevention of IgM-to-IgG anti-HLA class II antibody switching. CONCLUSIONS: T-cell-dependent B-cell isotype switching and the consequent production of IgG anti-HLA class II antibodies are strongly correlated with acute cellular rejection, a high incidence of recurrent rejections, TCAD, and poor long-term survival. Detecting this isotype switch is a clinically useful surrogate marker for in vivo T-cell activation and may provide a noninvasive approach for monitoring the efficacy of T-cell targeted immunosuppressive therapy in heart transplant recipients.

Adult↗